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Abstract: Some but not all patients with Tolosa–Hunt syndrome (THS) have dramatic responses to steroid treatment. A systematic study about the factors that may influence the steroid response of THS patients has not been published. We retrospectively identified 40 patients diagnosed with THS and treated with steroids with respect to patient age at onset, gender, the cranial nerve(s) involved, as well as imaging findings and laboratory tests. Within the context of these data we evaluated the therapeutic efficacy of steroid treatment and recurrence of attacks. We did not note a significant relationship between genders, whether THS was benign or inflammatory, the distribution of cranial nerve palsies, the initial dose of steroids and the effectiveness of steroid treatment for relief of orbital pain or cranial nerve palsies at 72h or 1week after treatment. Our study reveals that a rapid alleviation of pain by steroid treatment is a characteristic feature of THS patients. The alleviation of cranial nerve palsy is somewhat slower and more variable, and may involve additional mechanisms. There is an effect of patient age and whether attacks will recur (recurrence was more likely in patients who were young at the time of first attack), whether THS will be benign or inflammatory (more likely to be inflammatory in young patients) and the short-term response of cranial nerve palsy to steroid treatment, which was more effective in young patients. These relationships may be of value in counseling patients presenting with THS. [Copyright &y& Elsevier]

Objectives: Coronary artery disease (CAD) severity is associated with patient prognosis. However, few efficient scoring systems have been developed to screen severe CAD in patients with stable angina and suspected CAD before coronary angiography. Here, we present a novel scoring system for CAD severity before elective coronary angiography. Methods: Five hundred fifty-one patients with stable angina who were admitted for coronary angiography were enrolled in this study. Patients were divided into training (n = 347) and validation (n = 204) cohorts. Severe CAD was defined as having a Gensini score of 20 or more. All patients underwent echocardiography (ECG) to detect ejection fraction and aortic valve calcification (AVC). Multivariable analysis was applied to determine independent risk factors and develop the scoring system. Results: In the training cohort, age, male sex, AVC, abnormal ECG, diabetes, hyperlipidemia, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were identified as independent factors for severe CAD by multivariable analysis, and the Severe Prediction Scoring (SPS) system was developed. C-indices of receiver operating characteristic (ROC) curves for severe CAD were 0.744 and 0.710 in the training and validation groups, respectively. The SPS system also performed well during calibration, as demonstrated by Hosmer-Lemeshow analysis in the validation group. Compared with the Diamond-Forrester score, the SPS system performed better for severe CAD prediction before elective coronary angiography. Conclusions: Severe CAD prediction was achieved by analyzing age, sex, AVC, ECG, diabetes status, and lipid levels. Angina patients who achieve high scores using this predicting system should undergo early coronary angiography. [ABSTRACT FROM AUTHOR]

Little is known about the outcome for HIV-associated Hodgkin lymphoma (HIV-HL) as this is less common than HIV-negative lymphoma. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-HL patients in China. Nineteen cases of HIV-HL were diagnosed and treated at three center and including the sixth people's hospital of Zhengzhou, Peking union medical college hospital, and Chongqing university cancer hospital, between December 2013 and June 2022. Data on the clinical features, laboratory results, response, and prognosis were collected and analyzed. The median age at diagnosis was 43(22–74) years. All patients were infected with HIV through sexual transmission, with ten cases transmitted through man having sex with man (MSM) and nine cases transmitted through heterosexual transmission. Seven patients were diagnosed with lymphoma and found to be infected with HIV. Four cases were in stage III, and fifteen cases were in stage IV. After a median follow up of 46.8(4.0-112.9) months, 17 cases were alive after ABVD regimen chemotherapy combined with combination antiretroviral therapy (cART). The 5-year progression-free survival (PFS) and overall survival (OS) rate were 83.9% and 89.5%,respectively. HIV-HL exhibits an invasive process in clinical practice, and cART combined with ABVD regimen chemotherapy can achieve long-term survival for patients. [ABSTRACT FROM AUTHOR]

The gut microbiome (GMB) has been extensively reported to be associated with the development and prognosis of human diseases. This study aims to investigate the relationship between GMB composition and chemotherapy efficacy in diffuse large B-cell lymphoma (DLBCL). We demonstrated that DLBCL patients at diagnosis have altered GMB compositions. Significant enrichment of the Proteobacteria phylum in DLBCL patients was observed. Gene analysis showed a high abundance of virulence factors genes. We found baseline GMB to be associated with clinical outcomes. The emergence of Lactobacillus fermentum was correlated with better treatment outcome. Our pilot results suggested a correlation between GMB composition and DLBCL development and prognosis. Clues from our study, together with previous research, provided a rational foundation for further investigation on the pathogenesis, prognosis value, and targeted therapy of GMB in DLBCL. [ABSTRACT FROM AUTHOR]

The genome-wide profiling of 5-hydroxymethylcytosines (5hmC) on circulating cell-free DNA (cfDNA) has revealed promising biomarkers for various diseases. The purpose of this study was to investigate 5hmC signals in serum cfDNA and identify novel predictive biomarkers for the development of chemoresistance in high-grade serous ovarian cancer (HGSOC). We hypothesized that 5hmC profiles in cfDNA reflect the development of chemoresistance and elucidate pathways that may drive chemoresistance in HGSOC. Moreover, we sought to identify predictors that would better stratify outcomes for women with intermediate-sensitive HGSOC. Women diagnosed with HGSOC and known platinum sensitivity status were selected for this study. Nano-hmC-Seal was performed on cfDNA isolated from archived serum samples, and differential 5hmC features were identified using DESeq2 to establish a model predictive of chemoresistance. A multivariate model consisting of three features (preoperative CA-125, largest residual implant after surgery, 5hmC level of OSGEPL) , stratified samples from intermediate sensitive, chemo-naive women diagnosed with HGSOC into chemotherapy-resistant- and sensitive-like strata with a significant difference in overall survival (OS). Independent analysis of The Cancer Genome Atlas data further confirmed that high OSGEPL1 expression is a favorable prognostic factor for HGSOC. We have developed a novel multivariate model based on clinico-pathologic data and a cfDNA-derived 5hmC modified gene, OSGEPL1 , that predicted response to platinum-based chemotherapy in intermediate-sensitive HGSOC. Our multivariate model applies to chemo-naïve samples regardless if the patint was treated with adjuvant or neoadjuvant chemotherapy. These results merit further investigation of the predictive capability of our model in larger cohorts. • Chemotherapy does not alter global 5hmC deposition patterns on genomic features. • Neoadjuvant-treated platinum resistant disease is enriched in pathways associated with cellular responses to stress. • Adjuvant-treated platinum resistant disease is enriched in pathways associated with drug- and metabolism pathways. • An adjuvant chemotherapy-specific model stratifies intermediate sensitive disease into resistant- and sensitive-like groups. [ABSTRACT FROM AUTHOR]

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive B-cell non-Hodgkin lymphoma that poses a great diagnostic challenge due to its highly heterogenous clinical manifestations. Although 18F-fluorodeoxyglucose (FDG) is widely used as a diagnostic tool for patients suspected of having lymphoma, as it reveals FDG-avid lesions, the FDG avidity of IVLBCL has not been extensively characterized. Here, we present a comprehensive report of FDG avidity in IVLBCL and its association with clinicopathological features and survival. This descriptive observational study included consecutive patients aged at least 18 years diagnosed with IVLBCL in Peking Union Medical Hospital across 9 years. Among 50 screened IVLBCL patients, 42 had undergone 18F-FDG PET/CT to detect possible lesions for biopsy before pathological diagnosis; their FDG PET/CT (positron emission computed tomography, PET/CT) reports were retrospectively reviewed. The primary endpoint was the clinical description of FDG avidity of newly diagnosed intravascular large B-cell lymphoma and frequency. A total of 73.8% patients showed FDG-avid lesions, with a median SUVmax of 7.4 (range 1–27.7), which was lower than that for other aggressive lymphomas. Clinicopathological features were the same between the FDG-avid group and the non-FDG-avid group, except that the latter had a higher Ki-67 index (median 90% in the nonavid group vs. 80% in the avid group, P = 0.043). The overall survival rate was not different between the PET/CT groups. Our findings demonstrate that FDG PET/CT is a useful diagnostic tool for detecting FDG-avid lesions in IVLBCL patients. A random skin biopsy is essential for assisting in the diagnosis of IVLBCL, even for those with negative PET/CT. [ABSTRACT FROM AUTHOR]

Abstract: Papillary renal cell carcinoma (PRCC) includes two different morphological subtypes. The differences of genetics and ultrastructure of the two subtypes have been rarely reported. Also, new biomarkers related to the diagnosis and prognosis of PRCC have still not been well elucidated. Immunohistochemistry, fluorescence in situ hybridization (FISH) and transmission electron microscopy were used systematically to determine the characteristics of 56 cases of PRCC and to reveal new diagnostic and prognostic information. Type 1 PRCC presented higher expression rates of EMA and CK7, whereas type 2 presented a higher expression rate of CD10. New immunohistochemical markers, including: p504s, PAX-2, PAX-8 and CA-IX showed extensive immunostaining in PRCC. We first revealed a distinct immunostaining pattern of CA-IX, which was located in multiple foci in PRCC. All tumors had at least one chromosomal aberration including loss of Y, gains of 7 or 17. Gain of chromosome 17 was common in type 1; losses of chromosome 18, 11 and 8 appeared in type 2. Ultrastructurally, glycogen granules and secondary lysosomes were seen in type 1, mitochondria and smooth endoplasmic reticulum were scattered in type 2. Tumor subtype, nuclear grade, TNM stage, clear cell renal cell carcinoma (CCRCC) component and sarcomatoid elements, metastasis, CAIX expression, losses of chromosome 18 and 8 were related to poor outcome of PRCC. We conclude that the two subtypes of PRCC originate from different renal cells, and arise from partially common genetic pathways. EMA, CK7, CD10, p504s, PAX-2, PAX-8 and CA-IX are helpful markers in the differential diagnosis of PRCC. CA-IX expression, losses of chromosome 18 and 8 are new prognostic factors of PRCC. [Copyright &y& Elsevier]

BACKGROUND: More reliable clinical outcome prediction is required to better guide more personalized treatment for patients with primary glioblastoma multiforme (GBM). The objective of this study was to identify a microRNA expression signature to improve outcome prediction for patients with primary GBM. METHODS: A cohort of Chinese patients with primary GBM (n = 82) was analyzed using whole-genome microRNA expression profiling with patients divided into a training set and a testing set. Cox regression and risk-score analyses were used to develop a 5-microRNA signature using 41 training samples. The signature was validated in 41 other test samples, in an independent cohort of 35 patients with GBM, and in the Cancer Genome Atlas data set. RESULTS: Patients who had high risk scores according to the 5-microRNA signature had poor overall survival and progression-free survival compared with patients who had low risk scores. Multivariate Cox analysis indicated that the 5-microRNA signature was an independent prognostic biomarker after adjusting for other clinicopathologic and genetic factors, such as extent of resection, temozolomide chemotherapy, preoperative Karnofsky performance status score, isocitrate dehydrogenase 1 ( IDH1) mutation, and O-6-methylguanine-DNA methyltransferase ( MGMT) promoter methylation status. CONCLUSIONS: The 5-microRNA signature was identified as an independent risk predictor that identified patients who had a high risk of unfavorable outcome, demonstrating its potential for personalizing cancer management. The authors concluded that this signature should be evaluated in further prospective studies. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: To date, the aberrations in the DNA methylation patterns that are associated with different prognoses of G-CIMP− primary GBMs remain to be elucidated. Here, DNA methylation profiling of primary GBM tissues from 13 long-term survivors (LTS; overall survival ⩾18months) and 20 short-term survivors (STS; overall survival ⩽9months) was performed. Then G-CIMP+ samples were excluded. The differentially expressed CpG loci were identified between residual 18 STS and 9 LTS G-CIMP− samples. Methylation levels of 11 CpG loci (10genes) were statistically significantly lower, and 43 CpG loci (40genes) were statistically significantly higher in the tumor tissues of LTS than those of STS G-CIMP− samples (P <0.01). Of the 43 CpG loci that were hypermethylated in LTS G-CIMP− samples, 3 CpG loci localized in the promoter of ALDH1A3. Furthermore, using an independent validation cohort containing 37 primary GBM samples without IDH1 mutation and MGMT promoter methylation, the hypermethylation status of ALDH1A3 promoter predicted a better prognosis with an accompanied low expression of ALDH1A3 protein. Taken together, our results defined prognosis-related methylation signatures systematically for the first time in G-CIMP− primary GBMs. ALDH1A3 promoter methylation conferred a favorable prognosis in G-CIMP− primary GBMs. [Copyright &y& Elsevier]

Cytochrome P450 2E1 (CYP2E1) is an effective generator of reactive oxygen species. Marked expression of CYP2E1 occurs in the heart and it is known to be regulated in the course of progression of myocardial ischemia and cardiomyopathy. We provide evidence that the expression of CYP2E1 is strongly up-regulated in cTnT transgenic mice with dilated cardiomyopathy. Heart tissue-specific CYP2E1 transgenic mice were produced to study the effects of CYP2E1 overexpression on the heart. Increased mortality, chamber dilation and contractile dysfunction, as well as myocyte disarray, interstitial fibrosis, ultrastructural degeneration with myofibrillar disorganization and mitochondria damage, were observed in CYP2E1 transgenic mice and cTnT transgenic mice. In addition, levels of HO and malondialdehyde were increased and levels of glutathione and total antioxidant capability were strongly reduced in CYP2E1 transgenic mice and cTnT transgenic mice. Myocyte apoptosis was significantly increased by 19-fold in CYP2E1 transgenic mice and by 11-fold in cTnT transgenic mice, respectively, compared to wild-type mice. Mitochondrial-dependent apoptotic signal transduction events, such as cytochrome c release from mitochondria into the cytosol and the expression of cleaved (active) caspases 3 and 9, were significantly increased in CYP2E1 transgenic mice and cTnT transgenic mice. These results demonstrate that CYP2E1 over-expression produces apoptosis and that the up-regulation of CYP2E1 in cTnT transgenic mice also correlates with apoptosis in this model. Cytochrome P450 2E1 (CYP2E1) is an effective generator of reactive oxygen species. In this study we provided evidence that expression of CYP2E1 was strongly up-regulated in cTnT transgenic mice with dilated cardiomyopathy (DCM). The overexpression of CYP2E1 caused DCM phenotype, cardiac oxidative stress and myocyte apoptosis, all of which were similar to that in cTnT transgenic mice. [ABSTRACT FROM AUTHOR]

Gastric-type cervical adenocarcinoma (GCA) is a rare and aggressive type of endocervical adenocarcinoma (ECA) with distinct histopathologic features and unfavorable treatment outcomes, but no genomic prognostic factor has been revealed. We aimed to systematically investigate the somatic alterations of GCA at genome-wide level and evaluate their prognostic value. We performed whole-exome sequencing (WES) on 25 pairs of tumor and matched normal samples to characterize the genomic features of Chinese patients with GCA and investigated their relations to histopathological characterizations and prognosis. The prognostic value of the genomic alterations was evaluated in a total of 58 GCA patients. Mutations were commonly observed in reported GCA-related driver genes, including TP53 (32%), CDKN2A (20%), SKT11 (20%), BRCA2 (12%), SMAD4 (12%), and ERBB2 (12%). Recurrent novel trunk mutations were also observed in PBRM1 (12%), FRMPD4 (12%), and NOP2 (8%) with high variant allele frequency. Moreover, enrichment of the APOBEC signature was attributed to frequent gain of somatic copy number alteration (SCNA) of APOBEC3B (20%), which perfectly matched the nuclear-positive staining of APOBEC3B through immunohistochemistry. In contrast, APOBEC3B alteration was absent in patients with conventional type of ECA (N = 52). Notably, positive APOBEC3B was consistently enriched in patients with favorable prognosis in both the discovery cohort and an additional 33 GCA patients, thus indicating a significant association with lower relapse risk of GCA independent of cancer stage (P = 0.02). Our results can aid understanding of the molecular basis of GCA in the Chinese population by providing genomic profiles and highlighting the potential prognostic value of APOBEC3B for GCA through routine clinical IHC. • Novel somatic mutations in several driver genes can be revealed in GCA by whole genome sequencing. • Somatic copy number gain of APOBEC3B was common in GCA, which is rare in conventional endocervical cancer. • Positive immunohistochemistry staining of APOBEC3B can be served as biomarker for favorable prognosis of GCA. [ABSTRACT FROM AUTHOR]

• Radiomics is to provide and combine quantitative features of medical imaging to characterize tumor phenotypes, which may contribute to oncologic classification and prediction. • Dual-region signature, derived from primary neoplasm and regional lymph node from CT images, could offer incremental prognostic value over existing single radiomics signature for predicting overall survival in patients with esophageal squamous cell cancer. • To provide a promising tool for selecting appropriate treatment strategies and improve clinical outcomes of patients with ESCC. Preoperative prognostic biomarkers to guide individualized therapy are still in demand in esophageal squamous cell cancer (ESCC). Some studies reported that radiomic analysis based on CT images has been successfully performed to predict individual survival in EC. The aim of this study was to assess whether combining radiomics features from primary tumor and regional lymph nodes predicts overall survival (OS) better than using single-region features only, and to investigate the incremental value of the dual-region radiomics signature. In this retrospective study, three radiomics signatures were built from preoperative enhanced CT in a training cohort (n = 200) using LASSO Cox model. Associations between each signature and survival was assessed on a validation cohort (n = 107). Prediction accuracy for the three signatures was compared. By constructing a clinical nomogram and a radiomics-clinical nomogram, incremental prognostic value of the radiomics signature over clinicopathological factors in OS prediction was assessed in terms of discrimination, calibration, reclassification and clinical usefulness. The dual-region radiomic signature was an independent factor, significantly associated with OS (HR: 1.869, 95% CI: 1.347, 2.592, P = 1.82e-04), which achieved better OS (C-index: 0.611) prediction either than the single-region signature (C-index:0.594-0.604). The resulted dual-region radiomics-clinical nomogram achieved the best discriminative ability in OS prediction (C-index:0.700). Compared with the clinical nomogram, the radiomics-clinical nomogram improved the calibration and classification accuracy for OS prediction with a total net reclassification improvement (NRI) of 26.9% (P =0.008) and integrated discrimination improvement (IDI) of 6.8% (P <0.001). The dual-region radiomic signature is an independent prognostic marker and outperforms single-region signature in OS for ESCC patients. Integrating the dual-region radiomics signature and clinicopathological factors improves OS prediction. [ABSTRACT FROM AUTHOR]

Intelligent data-driven system prognostic methods have been popularly developed in the recent years. Despite the promising results, most approaches assume the training and testing data are from the same operating condition. In the real industries, it is quite common that different machine entities work under different scenarios, that results in performance deteriorations of the data-driven prognostic methods. This paper proposes a transfer learning method for remaining useful life predictions using deep representation regularization. The practical and challenging scenario is investigated, where the training and testing data are from different machinery operating conditions, and no target-domain run-to-failure data is available for training. In the deep learning framework, data alignment schemes are proposed in the representation sub-space, including healthy state alignment, degradation direction alignment, degradation level regularization and degradation fusion. In this way, the life-cycle data of different machine entities across domains can follow the same degradation trace, thus achieving prognostic knowledge transfer. Extensive experiments on the aero-engine dataset validate the effectiveness of the proposed method, which offers a promising solution for industrial prognostics. • The cross-domain remaining useful life prediction problem is investigated. • A deep learning-based transfer learning method is proposed for prognostics. • The target domains only include unlabeled data at early degradation periods. • Deep representation regularization schemes are proposed for data alignments. • Experiments validate the effectiveness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

Background. Non-small-cell lung carcinoma (abbreviated as NSCLC) progresses rapidly and lacks appropriate biological markers. Recent studies have shown that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) has potential application value for clinically diagnosing lung carcinoma. Thus, this study conducted a systematic review and meta-analysis for assessing if MALAT-1 has a relationship to NSCLC outcome. Methods. This study conducted the search of China National Knowledge Infrastructure, China Science and Technology Journal, SinoMed, EMBASE, Cochrane library, Web of Science, Wanfang database, and PubMed from inception to September, 1, 2021. The published article about MALAT-l expression for NSCLC patients was analyzed. We used combined hazard rates under the confidence interval of 95% for examining the relationship of MALAT-l and NSCLC.Results. In this meta-analysis, we found that 10 studies were included, and MALAT-1 expressions were distinctly related to an unfavorable overall survival (HR: 2.34 (1.65, 3.33); I2 = 76%). Considering the merger's clinical heterogeneity, for meta-analysis, we used the random-effects method. Conclusion. Overexpression of MALAT-1 showed correlations to the less effective outcome of NSCLC. MALAT-1 might be a new NSCLC prognosis marker. [ABSTRACT FROM AUTHOR]

Background: Tissue-resident memory T (TRM) cells can reside in the tumor microenvironment and are considered the primary response cells to immunotherapy. Heterogeneity in functional status and spatial distribution may contribute to the controversial role of TRM cells but we know little about it. Methods: Through multiplex immunofluorescence (mIF) (CD8, CD103, PD-1, Tim-3, GZMB, CK), the quantity and spatial location of TRM cell subsets were recognized in the tissue from 274 patients with NSCLC after radical surgery. By integrating multiple machine learning methods, we constructed a TRM-based spatial immune signature (TRM-SIS) to predict the prognosis. Furthermore, we conducted a CD103-related gene set enrichment analysis (GSEA) and verified its finding by another mIF panel (CD8, CD103, CK, CD31, Hif-1α). Results: The density of TRM cells was significantly correlated with the expression of PD-1, Tim-3 and GZMB. Four types of TRM cell subsets was defined, including TRM1 (PD-1−Tim-3−TRM), TRM2 (PD-1+Tim-3−TRM), TRM3 (PD-1−Tim-3+TRM) and TRM4 (PD-1+Tim-3+TRM). The cytotoxicity of TRM2 was the strongest while that of TRM4 was the weakest. Compare with TRM1 and TRM2, TRM3 and TRM4 had better infiltration and stronger interaction with cancer cells. The TRM-SIS was an independent prognostic factor for disease-free survival [HR = 2.43, 95%CI (1.63–3.60), P < 0.001] and showed a better performance than the TNM staging system for recurrence prediction. Furthermore, by CD103-related GSEA and mIF validation, we found a negative association between tumor angiogenesis and infiltration of TRM cells. Conclusions: These findings reveal a significant heterogeneity in the functional status and spatial distribution of TRM cells, and support it as a biomarker for the prognosis of NSCLC patients. Regulating TRM cells by targeting tumor angiogenesis may be a potential strategy to improve current immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study are to clarify clinical characteristics and recognize prognostic factors of CTD-PAH patients. Methods: A retrospective cohort study of consecutive patients with documented CTD-PAH diagnosis from Jan 2014 to Dec 2019 was conducted, the ones who have other comorbid conditions that cause PH were excluded. Survival functions were plotted using the Kaplan–Meier method. Univariable and multivariable Cox regression analysis was applied to determine the survival-related factors. Results: In 144 patients with CTD-PAH analyzed, the median sPAP value was 52.5 (44.0, 71.0) mmHg, the overall targeted drug usage rate was 55.6%, and only 27.5% patients were given combination. Twenty-four non-PAH-CTD patients with sPAP value were included as the control group. Compared with non-PAH-CTD groups, CTD-PAH patients had worse cardiac function, higher NT-pro BNP and γ-globulin level, and lower PaCO2 level. Compared with the mild PAH group, the moderate-severe PAH group had worse cardiac function; increased Hb, HCT, and NP-pro BNP level; and decreased PaO2. Kaplan–Meier analysis showed significant difference for survival among non-PAH-CTD, mild CTD-PAH, and moderate-severe CTD-PAH groups. The univariate analyses showed that Hb, pH, and Ln (NT-pro BNP) were identified as factors significantly associated with survival, and Hb and pH showed significant association with risk of death in the multivariate model. Kaplan–Meier analysis also showed that Hb > 109.0 g/L and pH > 7.457 affected CTD-PAH patients' survival significantly. Conclusions: PAH is not rare in CTDs patients; PAH affects CTD patients' prognosis significantly. Higher Hb and pH were associated with an increased risk of death. Key Points • Pulmonary arterial hypertension affects connective tissue disease patients' prognosis significantly. • The significantly factors associated with survival is hemoglobin, pH, and Ln (NT-pro BNP). [ABSTRACT FROM AUTHOR]

Objective: LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance and prognosis of ovarian cancer was confirmed in experiments. Methods: Multiple databases have performed the bioinformatics analysis of methylation and transcription factor binding site (TFBS) on the promoter region of LAMA3 gene. Pyrosequencing detected the methylation of LAMA3. QRT-PCR and immunohistochemistry detected the expression of LAMA3. Real Time Cell Analyzer (RTCA) detects changes in cell proliferation, migration and invasion ability. Flow cytometry was used to detect apoptosis. Results: CPG islands of 176 bp, 134 bp, 125 bp and 531 bp were predicted in the promoter region of LAMA3 gene. The 4 prediction results are basically overlapped. 7 transcription factor binding sites were predicted, and the one with the highest score was on the predicted CpG island located in the proximal promoter region. LAMA3 hypermethylation and low expression are both associated with chemotherapy resistance and poor prognosis in ovarian cancer. LAMA3 methylation was negatively correlated with expression. After upregulation of LAMA3, the proliferation ability of chemoresistant ovarian cancer cell decreased, while the ability of apoptosis, invasion and migration increased. Conclusion: LAMA3 hypermethylation is associated with chemotherapy resistance and poor prognosis. As a typical CpG island gene, LAMA3(cg20937934) and LAMA3(cg13270625) hypermethylation is negatively correlated with low expression. LAMA3 promotes the invasion, migration and apoptosis of SKOV3DDP. In the future, the mechanism of LAMA3 methylation in ovarian cancer will need to be further studied. [ABSTRACT FROM AUTHOR]

Background: Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factor remains unclear.Methods: 178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method.Results: There was no significant difference in OS between T2a and T2b groups, and the median OS duration were 37 and 31 months (P = 0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of preoperative AST (≥85.0 IU/L) and CA19-9 (≥1000 U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection.Conclusion: The newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b pCCA after resection. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 49-year-old man diagnosed with polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndromecaused by renal failure. The clinical examination of the patient shows his POEMS syndrome's poor prognosis. The safety and effectiveness of combined dexamethasone and bortezomib for the patients is also pointed out.

Background: Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking.Methods: We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell's C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers.Results: Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30-50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management.Conclusions: The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram. [ABSTRACT FROM AUTHOR]

Background: SH2 domain containing 1A (SH2D1A) expression has been linked to cancer progression. However, the functions of SH2D1A in hepatocellular carcinoma (HCC) have not been reported. Methods: The effects of SH2D1A on the proliferation, migration, and invasion of HCC cells and the related pathways were re-explored in cell models with SH2D1A overexpression using the CCK-8, migration and invasion assays and western blotting. The functions and mechanisms of genes co-expressed with SH2D1A were analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The relationship between SH2D1A expression and immune microenvironment features in HCC was explored. Results: Elevated SH2D1A expression promoted cell proliferation, migration, and invasion, which was related to the overexpression of p-Nf-κB and BCL2A1 protein levels in HCC. SH2D1A expression was related to the immune, stromal, and ESTIMATE scores, and the abundance of immune cells, such as B cells, CD8+ T cells, and T cells. SH2D1A expression was significantly related to the expression of immune cell markers, such as PDCD1, CD8A, and CTLA4 in HCC. Conclusion: SH2D1A overexpression was found to promote cell growth and metastasis via the Nf-κB signaling pathway and may be related to the immune microenvironment in HCC. The findings indicate that SH2D1A can function as a biomarker in HCC. [ABSTRACT FROM AUTHOR]

Purpose: The rise of female breast cancer has created a significant global public health issue that requires effective solutions. Disulfidptosis, a recently identified form of cell death characterized by an excessive accumulation of disulfides, has unique initiatory and regulatory mechanisms. The formation of disulfide bonds is a metabolic event typically associated with cysteines. This study aims to explore the potential of the affinity between cysteine metabolism and disulfidptosis in risk stratification for breast invasive carcinoma (BRCA). Methods: We used correlation analysis to decipher co-relation genes between cysteine metabolism and disulfidptosis (CMDCRGs). Both LASSO regression analysis and multivariate Cox regression analysis were employed to construct the prognostic signature. Additionally, we conducted investigations concerning subtype identification, functional enhancement, mutation landscape, immune infiltration, drug prioritization, and single-cell analysis. Results: We developed and validated a six-gene prognostic signature as an independent prognostic predictor for BRCA. The prognostic nomogram, based on risk score, demonstrated a favorable capability in predicting survival outcomes. We identified distinct gene mutations, functional enhancements, and immune infiltration patterns between the two risk groups. Four clusters of drugs were predicted as potentially effective for patients in the low-risk group. We identified seven cell clusters within the tumor microenvironment of breast cancer, and RPL27A was found to be widely expressed in this environment. Conclusion: Multidimensional analyses confirmed the clinical utility of the cysteine metabolism-disulfidptosis affinity-based signature in risk stratification and guiding personalized treatment for patients with BRCA. [ABSTRACT FROM AUTHOR]

Introduction: Knowledge is limited regarding the significance of pulmonary arterial pressure (PAP) in predominantly congenital mitral valve regurgitation (MR)-based intracardiac abnormalities. Methods: From a prospective cohort, we included 200 patients with congenital MR regardless of other associated intracardiac abnormalities (mean age 60.4 months, 67% female, systolic PAP (sPAP) 54.2 mm Hg) surgically repaired in 2012–2019 and followed up to 2020 (median 30.0 months). Significant pulmonary hypertension (PH) was defined as sPAP >50 mm Hg at rest or mean PAP >25 mm Hg on right heart catheterization. By perioperative sPAP changes, patients were stratified as group I (pre-normotension to post-normotension), group II (pre-hypertension to post-normotension), or group III (pre-hypertension to post-hypertension). Primary outcomes were the recurrence of MR (defined as the regurgitation grade of moderate or greater) and the progression of MR (defined as any increase in the magnitude of regurgitation grade after surgery). Cox proportional hazard and Kaplan-Meier curve were performed. Results: There was no association between preoperative PH and the recurrent MR (adjusted hazard ratios [aHR]: 1.146 [95% CI: 0.453–2.899]) and progressive MR (aHR: 1.753 [95% CI: 0.807–3.804]), respectively. There were no significant differences among group I, group II, and group III in the recurrent MR but in the progressive MR. A dose dependency was identified for preoperative sPAP with recurrent MR (aHR: 1.050 [95% CI: 1.029–1.071]) and progressive MR risks (aHR: 1.037 [95% CI: 1.019–1.055]), respectively. Conclusions: Preoperative higher sPAP is associated with worse outcomes, warranting heightened attention to the identification of perioperative sPAP. [ABSTRACT FROM AUTHOR]

Background: Whether serum lactate dehydrogenase-to-albumin ratio (LAR) influenced the outcomes of colorectal cancer (CRC) patients after radical surgery remained unclear. Therefore, this study sought to examine how LAR influences the short-term and long-term outcomes of CRC patients who have undergone radical surgery. Methods: This study retrospectively included CRC patients who underwent radical resection between January 2011 and January 2020. We compared short-term outcomes, as well as overall survival (OS) and disease-free survival (DFS), among various groups. Both univariate and multivariate logistic regression analyses were utilized to pinpoint independent risk factors associated with overall complications and major complications. Moreover, Cox regression analysis were conducted for OS and DFS. Odds ratio (OR) and Hazard ratio (HR) were adjusted. Results: This study encompassed a cohort of 3868 patients. 3440 patients were in the low LAR group and 428 patients constituted the high LAR group. In the high LAR group, patients experienced significantly longer operative times (p < 0.01), larger intraoperative blood loss (p < 0.01), and extended postoperative hospital stays (p < 0.01). Additionally, the incidence of both overall complications (p < 0.01) and major complications (p < 0.01) was higher in the high LAR group compared to the low LAR group. Furthermore, LAR was emerged as an independent prognostic factor for overall complications [OR/95% CI: (1.555/1.237 to 1.954), p < 0.01] and major complications [OR/95% CI: (2.178/1.279 to 3.707), p < 0.01]. As for long-term survival, the high LAR group had worse OS in stage II (p < 0.01) and stage III (p < 0.01). In both stage II (p < 0.01) and stage III (p < 0.01), the high LAR group exhibited poorer DFS. Additionally, according to Cox regression analysis, LAR was identified as an independent predictor for both OS [HR/95% CI: (1.930/1.554 to 2.398), p < 0.01] and DFS [HR/95% CI: (1.750/1.427 to 2.146), p < 0.01]. Conclusion: LAR emerged as an independent predictor not only for overall complications and major complications but also for both OS and DFS, highlighting its significance and deserving the attention of surgeons. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus erythematosus-associated pulmonary arterial hypertension. Research question: To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. Methods: A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping. Results: Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67–7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making. Conclusions: This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model's predictions in diverse patient populations. [ABSTRACT FROM AUTHOR]

Background: Tertiary lymphoid structures (TLSs), as ectopic lymphoid-like tissues, are highly similar to secondary lymphoid organs and are not only involved in chronic inflammation and autoimmune responses but are also closely associated with tumor immunotherapy and prognosis. The complex composition of the urological tumor microenvironment not only varies greatly in response to immunotherapy, but the prognostic value of TLSs in different urological tumors remains controversial. Summary: We searched PubMed, Web of Science, and other full-text database systems. TLSs, kidney cancer, uroepithelial cancer, bladder cancer, and prostate cancer as keywords, relevant literature was searched from the time the library was built to 2023. Systematically explore the role and mechanism of TLSs in urological tumors. It includes the characteristics of TLSs, the role and mechanism of TLSs in urological tumors, and the clinical significance of TLSs in urological tumors. Key Messages: The prognostic role of TLSs in different urological tumors was significantly different. It is not only related to its enrichment in the tumor but also highly correlated with the location of the tumor. In addition, autoimmune toxicity may be a potential barrier to its role in the formation of TLSs through induction. Therefore, studying the mechanisms of TLSs in autoimmune diseases may help in the development of antitumor target drugs. [ABSTRACT FROM AUTHOR]

Background: Grade 4 glioma is the most aggressive and currently incurable brain tumor with a median survival of one year in adult patients. Elucidating novel transcriptomic and epigenetic contributors to the molecular heterogeneity underlying its aggressiveness may lead to improved clinical outcomes. Methods: To identify grade 4 glioma -associated 5-hydroxymethylcytosine (5hmC) and transcriptomic features as well as their cross-talks, genome-wide 5hmC and transcriptomic profiles of tissue samples from 61 patients with grade 4 gliomas and 9 normal controls were obtained for differential and co-regulation/co-modification analyses. Prognostic models on overall survival based on transcriptomic features and the 5hmC modifications summarized over genic regions (promoters, gene bodies) and brain-derived histone marks were developed using machine learning algorithms. Results: Despite global reduction, the majority of differential 5hmC features showed higher modification levels in grade 4 gliomas as compared to normal controls. In addition, the bi-directional correlations between 5hmC modifications over promoter regions or gene bodies and gene expression were greatly disturbed in grade 4 gliomas regardless of IDH1 mutation status. Phenotype-associated co-regulated 5hmC–5hmC modules and 5hmC–mRNA modules not only are enriched with different molecular pathways that are indicative of the pathogenesis of grade 4 gliomas, but also are of prognostic significance comparable to IDH1 mutation status. Lastly, the best-performing 5hmC model can predict patient survival at a much higher accuracy (c-index = 74%) when compared to conventional prognostic factor IDH1 (c-index = 57%), capturing the molecular characteristics of tumors that are independent of IDH1 mutation status and gene expression-based molecular subtypes. Conclusions: The 5hmC-based prognostic model could offer a robust tool to predict survival in patients with grade 4 gliomas, potentially outperforming existing prognostic factors such as IDH1 mutations. The crosstalk between 5hmC and gene expression revealed another layer of complexity underlying the molecular heterogeneity in grade 4 gliomas, offering opportunities for identifying novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of Long Non-coding RNAs (lncRNAs) emerges to be a hallmark of cancers. Metastatic prostate cancer and localized disease that recurs after treatment are clinical challenges, it remains unclear how lncRNA plays a role in those processes. Methods: From previous RNA-Seq data on 65 prostate cancer and adjacent normal tissues. We identified a novel lncRNA ENST00000503625 down-regulated in prostate cancer and correlated with tumor progression characteristics. Public datasets were examined for associations between ENST00000503625 expression and clinical parameters and prognoses. Subsequently, we constructed and externally validated a nomogram for predicting biochemical recurrence (BCR). Finally, in vitro experiments were carried out to determine how ENST00000503625 functions biologically in prostate cancer. Results: Low ENST00000503625 in tumor was associated with poor clinical features and prognoses. TCGA pan-cancer analysis found that ENST00000503625 was deregulated in a variety of tumors and correlated with overall survival, disease-specific survival, and progression-free survival. The nomogram for predicting BCR was constructed using TCGA data, which exhibited excellent accuracy in external validation with Chinese Prostate Cancer Genome and Epigenome Atlas data. Gene Ontology and KEGG pathway analysis found that genes related to ENST00000503625 were enriched in multiple tumor progression related pathways. When ENST00000503625 was knocked down in vitro, the epithelial-mesenchymal transition was induced, by which cancer cells migrated and invaded more readily. Conclusion: Our data suggested that ENST00000503625 may serve as a potential prognostic marker or a therapeutic target for prostate cancer metastases. [ABSTRACT FROM AUTHOR]

The dysregulation of alternative splicing (AS) has emerged as a mechanism of acute myeloid leukemia (AML). However, the prognostic impact of AS events remains under-explored in AML. Here we report the prognostic value of AS events and associated splicing factors based on three datasets of AML patients. We defined the landscape of AS events in AML and identified 7033 AS events associated with the survival of AML patients. Based on these events, we further developed a composite 15 AS event-based prognostic signature, which was independent of the cytogenetic risk stratification and patient age, and showed a better performance than known gene expression signatures. More importantly, our new signature markedly improved the European LeukemiaNet (ELN) risk classification, indicating a broad applicability in the clinical management of AML. Furthermore, the splicing-regulatory network established the correlations between prognostic AS events and associated splicing factors. The finding was validated by CRISPR-based data, which indicated that the increased expression of RBM39 contributed to the higher exon inclusion of SETD5 and conferred a poor outcome. Together, AS events may serve as a novel assortment of prognosticators for AML and could refine the ELN risk stratification. The splicing regulatory network provides clues regarding the splicing factor-mediated mechanisms of AML. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC), which was one of the most common malignant tumors in urinary system, had gradually increased incidence and mortality in recent years. Although significant advances had been made in molecular and biology research on the pathogenesis of RCC, effective treatments and prognostic indicators were still lacking. In order to predict the prognosis of RCC better, we identified 17 genes that were associated with the overall survival (OS) of RCC patients from The Cancer Genome Atlas (TCGA) dataset and a 17-gene signature was developed. Through SurvExpress, we analyzed the expression differences of the 17 genes and their correlation with the survival of RCC patients in five datasets (ZHAO, TCGA, KIPAN, KIRC, and KIRP), and then evaluated the survival prognostic significance of the 17-gene signature for RCC. Our results showed that the 17-gene signature had a predictive prognostic value not only in single pathologic RCC, but also in multiple pathologic types of RCC. In conclusion, the 17-gene signature model was related to the survival of RCC patients and could help predict the prognosis with significant clinical implications. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to explore whether liver cirrhosis (LC) influences short-term and long-term outcomes in gastric neoplasm patients who undergo endoscopic submucosal dissection (ESD). Materials and Methods: Eligible studies were identified in three databases, including PubMed, Embase, and the Cochrane Library on December 18, 2022. Clinical characteristics, short-term outcomes, and long-term outcomes were compared between an LC group and a no liver cirrhosis (NLC) group. For continuous variables, the mean difference (MD) and standard deviation (SD) were pooled. For discontinuous variables, raw data from the 2 × 2 tables or odds ratio (OR) and 95% confidence intervals (CIs) were pooled. Forest plots were used to show the results, and a funnel plot was used to evaluate publication bias. Data analyses were performed by STATA SE 16.0 software. Results: Six retrospective studies involving 1616 gastric neoplasm patients were included in the study. Clinical characteristics, including age, gender, location, macroscopic type, invasion depth, differentiation, and ulceration, were found to be not significantly different between the LC group and the NLC group (P > .05). Moreover, LC was not a risk factor for short-term outcomes, including operative time (MD = 0.15, 95% CI = −0.02 to 0.32, I2 = 0.00%, P = .09), en bloc resection (OR = 0.87, 95% CI = 0.43–1.75, I2 = 0.00%, P = .69), R0 resection (OR = 0.77, 95% CI = 0.42–1.43, I2 = 8.97%, P = .41), bleeding (OR = 1.10, 95% CI = 0.62–1.93, I2 = 0.00%, P = .75), and perforation (OR = 1.62, 95% CI = 0.45–5.84, I2 = 0.00%, P = .46). However, gastric cancer patients with LC exhibited a higher recurrence rate (OR = 3.40, 95% CI = 1.09–10.61, I2 = 0.00%, P = .04) after ESD. Conclusion: Surgeons performing ESD in gastric neoplasm patients should pay more attention to long-term effects. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the influence of type 2 diabetes mellitus (T2DM) on stage IV colorectal cancer (CRC) patients performed primary surgery in terms of short-term and long-term outcomes. Methods: Patients diagnosed with stage IV CRC and received primary CRC surgery at a single clinical center from Jan, 2013 to Jan, 2020 were included in this study. Baseline characteristics, short-term and long-term outcomes were compared between the T2DM group and the Non-T2DM group. Univariate and multivariate analysis were used to find risk factors for overall survival (OS). Propensity score matching (PSM) using a 1:1 ratio was used to minimize selective bias between the two groups. Statistical analysis was performed using SPSS (version 22.0) software. Results: A total of 302 eligible patients were enrolled, and there were 54 (17.9%) patients with T2DM, and 248 (82.1%) patients without T2DM. The T2DM group had more older patients (P < 0.01), higher body mass index (BMI) (P < 0.01), and a higher proportion of hypertension (P < 0.01) than the Non-T2DM group. After PSM, there were 48 patients in each group. There were no significant differences in short-term outcomes or OS between the two groups, either before or after PSM (P > 0.05). In multivariate analysis, older age (P < 0.01, HR = 1.032, 95% CI = 1.014–1.051) and larger tumor size (P < 0.01, HR = 1.760, 95% CI = 1.179–2.626) were independent factors for OS. Conclusion: Although T2DM did not influence short-term outcomes or OS in stage IV CRC patients after primary surgery, age and tumor size might have predictive value for OS. [ABSTRACT FROM AUTHOR]

Background: Tenascin-C is a pro-inflammatory glycoprotein with various biological functions. High expression of tenascin-C is found in inflammation, tissue remodeling, and autoimmune diseases. However, its expression and clinical significance in sepsis remain unclear. This study was designed to investigate the relationship between serum tenascin-C levels and disease severity and prognosis in patients with sepsis. Methods: A total of 167 patients with sepsis admitted to the ICU were enrolled. Lood samples were collected within 24 h of admission. Serum tenascin-C levels were measured by enzyme-linked immunosorbent assay (ELISA). Follow-up was performed to observe 30-day mortality. Results: Serum tenascin-C levels were significantly elevated in patients with sepsis compared with non-sepsis controls (P < 0.001). Serum tenascin-C levels were higher in nonsurvivors (58 cases) who died within 30 days (34.5%) compared to survivors (109 cases) (P < 0.001). In patients with sepsis, serum tenascin-C levels were significantly positively correlated with SOFA scores (P = 0.011), serum creatinine (P = 0.006), C-reactive protein (CRP) (P = 0.001), interleukin-6 (IL-6) (P < 0.001), and tumor necrosis factor α (TNF-α) (P = 0.026). Logistic multivariate regression models showed that serum tenascin-C levels were independent contributor of 30-day mortality. Kaplan-Meier curves showed that septic patients with high levels of serum tenascin-C (≥56.9 pg/mL) had significantly higher 30-day mortality than those with lower serum tenascin-C (< 56.9 pg/mL) (P < 0.001). Conclusion: Elevated serum tenascin-C was found in septic patients and associated with severity and poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Infection is a significant risk factor that impacts for perioperative morbidity and mortality in liver transplantation (LTx) patients and is difficult to evaluate quantitatively in the early posttransplantation period. Thus, a biomarker to assess the risk of infection and the prognosis of the recipient is highly desirable. Methods: A total of 128 consecutive patients with end‐stage liver diseases undergoing LTx between January 1, 2020 and December 31, 2021, at the First Affiliated Hospital of Zhejiang University School of Medicine, were screened retrospectively. Graft preservation fluid and blood samples were collected for culture, and other perioperative laboratory examination results were recorded, for assessment of infection status. Results: After a follow‐up period of 30 days, the survival rate among the 128 LTx recipients was 94.5%. Multivariable regression analysis showed that the logarithmically transformed neutrophil‐to‐lymphocyte ratio (NLR) (HR = 3.548, 95% CI: ; p =.041) on post‐LTx day 1 and graft preservation fluid culture positivity (HR = 12.032, 95% CI: ; p =.006) were independent predictive factors for early prognosis after LTx. Conclusions: Positive graft preservation fluid culture and the logarithmically transformed NLR on post‐LTx day 1 were independent predictive factors for early prognosis after LTx. The logarithmically transformed NLR could provide an earlier indication than culture results in clinical practice. [ABSTRACT FROM AUTHOR]

Background: This study aimed to better characterize the clinicopathologic characteristics, outcomes, and prognostic factors of AITL in China. Methods: We retrospectively analyzed 312 patients with AITL enrolled between January 2011 and December 2020 from five institutions in China. Results: The median age was 65 years, with 92.6% advanced stage, 59.7% elevated LDH, 46.1% anemia, and 44.0% hypergammaglobulinemia. The majority of patients (84.9%) received anthracycline‐based regimens with or without etoposide, and only 6.1% underwent autologous stem cell transplantation following first remission. The 5‐year OS and PFS estimates were 43.4% and 25.0% with no significant improvement of survival between patients treated during 2011–2015 and 2016–2020, respectively. Both the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT), were predictive for OS. In multivariate analysis, age >70 years, elevated LDH, and albumin level <35 g/L were independent prognostic factors for OS. Combining these three factors, a novel prognostic model (the Chinese AITL score) was constructed, which stratified patients into low‐, intermediate‐, and high‐risk groups, with 5‐year OS rates of 69.0%, 41.5%, and 23.7%, respectively. This new model was successfully validated in an independent cohort. Conclusions: Patients with AITL were mainly treated with anthracycline‐based regimens, and the outcomes were still unsatisfactory in China. Our novel prognostic model may improve our ability to identify patients at different risks for alternative therapies. [ABSTRACT FROM AUTHOR]

The optimal timing and sequencing of radiotherapy (RT) and chemotherapy (CT) in the treatment of limited-stage extranodal NK/T cell lymphoma (LS-ENKTL) has not been elucidated. The aim of this meta-analysis was to evaluate whether the timing of RT in relation to CT affects the survival of patients with LS-ENKTL. We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov , and relevant meeting abstract databases from inception through April 2018 without age or language restrictions. Studies comparing upfront RT plus CT with induction CT followed by RT in patients with LS-ENTKL were eligible for inclusion. Seven studies with 1593 patients were included, and all were retrospective cohort studies. Compared with induction CT followed by RT, upfront RT significantly improved OS of patients with LS-ENTKL (HR = 0.70, 95%CI 0.55-0.88, P = 0.002), with no evidence of heterogeneity across studies (I2 = 0%). In subgroup analyses, the beneficial effect of upfront RT on survival did not differ significantly between subgroups of studies with different types of chemotherapy regimens (anthracycline-based or non-anthracycline-based), the administration of concurrent chemoradiotherapy or not, and different median doses of RT (≥ 45 or < 45 Gy). These results suggest that upfront RT plus CT confers survival advantage over induction CT followed by RT for the treatment of LS-ENTKL, and this survival advantage is not significantly affected by the types of CT regimens or timing of CT. Given the retrospective nature of included studies, these results should be interpreted with caution in clinical practice. [ABSTRACT FROM AUTHOR]

Background: To study metastasis to the infra-pyloric (no. 6) lymph nodes and their subgroups and the related risk factors of gastric cancer patients. Methods: Gastric cancer patients who underwent gastrectomy with complete postoperative pathological information on the no. 6 lymph node station and its subgroups from January 1, 2008, to December 31, 2011, were included. The clinicopathological characteristics and survival outcomes were analyzed. Results: A total of 121 patients were included; they had 6.1 ± 7.7 positive lymph nodes, and 35.1 ± 14.2 lymph nodes were examined. The overall lymph node positivity rate was 67.8% (82/121) with a positivity rate of 28.1% (34/121) for the no. 6 lymph nodes. The metastasis rate was 6.6% for the no. 6a nodes, 6.6% for the no. 6b nodes, and 21.5% for the no. 6c nodes. Also, no. 8a (OR = 1.329, p = 0.017) and no. 9 (OR = 1.250, p = 0.022) nodal positivity and lower third tumor location (OR = 1.278, p = 0.001) were independent risk factors for no. 6 lymph nodal metastasis. There was a significant survival difference between patients with positive and negative no. 6 lymph nodes and patients with metastasis to other lymph node stations (p < 0.001). Conclusions: Patients with no. 6 lymph node metastasis have poor survival outcomes. Complete infra-pyloric lymphadenectomy is necessary and crucial for gastric cancer patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nearly half of adult acute myeloid leukemia (AML) patients were classified into cytogenetic normal acute myeloid leukemia (CN-AML). The expression level of Trophinin associated protein (TROAP) was proven to be associated with the prognosis of several cancers, but it is still unclear in the prognosis of patients with CN-AML. METHODS: We integrated CN-AML patient samples from 4 datasets to analyze the relationship between TROAP expression and the survival of CN-AML. In addition, we investigated 92 AML patients of The Cancer Genome Atlas (TCGA) database to analyze the relationship between TROAP expression and the survival of AML patients received chemotherapy. We investigated the relationship between the expression of TROAP and drug sensitivity in AML cell lines. RESULTS: CN-AML patients with high TROAP expression were related to good event-free survival (EFS) and overall survival (OS). In AML patients received chemotherapy, high TROAP expression was associated with good survival prognosis. Additionally, the expression of TROAP gene in leukemia stem cells (LSC) + group was lower. Among multiple drugs, the lower the expression of TROAP, the lower the IC50. CONCLUSION: TROAP could serve as an independent predictor of CN-AML patients and could act as a potential biomarker for the prognosis of CN-AML. TROAP expression levels were closely correlated with the drug sensitivity of multiple drugs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Acute myeloid leukemia (AML) is a significantly heterogeneous malignancy of the blood. Cytogenetic abnormalities are crucial for the prognosis of AML. However, since more than half of patients with AML are cytogenetically normal AML (CN-AML), predictive prognostic indicators need to be further refined. In recent years, gene abnormalities are considered to be strong prognostic factors of CN-AML, already having clinical significance for treatment. In addition, the relationship of methylation in some genes and AML prognosis predicting has been discovered. RASGEF1A is a guanine nucleotide exchange factors of Ras and widely expressed in brain tissue, bone marrow and 17 other tissues. RASGEF1A has been reported to be associated with a variety of malignant tumors, examples include Hirschsprung disease, renal cell carcinoma, breast cancer, diffuse large B cell lymphoma, intrahepatic cholangiocarcinoma and so on [1, 2]. However, the relationship between the RASGEF1A gene and CN-AML has not been reported. METHODS: By integrating the Cancer Genome Atlas (TCGA) database 75 patients with CN-AML and 240 Gene Expression Omnibus (GEO) database CN-AML samples, we examined the association between RASGEF1A's RNA expression level and DNA methylation of and AML patients' prognosis. Then, we investigated the RASGEF1A RNA expression and DNA methylation's prognostic value in 77 patients with AML after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) as well as 101 AML patients after chemotherapy respectively. We investigated the association between sensitivity to Crenolanib and expression level of RASGED1A in patients by integrating 191 CN-AML patients from BeatAML dadataset. We integrated the expression and methylation of RASGEF1A to predict the CN-AML patients' prognosis and investigated the relationship between prognostic of AML patients with different risk classification and expression levels or methylation levels of RASGEF1A. RESULTS: We found that RASGEF1A gene high expression group predicted poorer event-free survival (EFS) (P < 0.0001) as well as overall survival (OS) (P < 0.0001) in CN-AML samples, and the identical results were found in AML patients receiving chemotherapy (P < 0.0001) and Allo-HSCT (P < 0.0001). RASGEF1A RNA expression level is an CN-AML patients' independent prognostic factor (EFS: HR = 5.5534, 95% CI: 1.2982–23.756, P = 0.0208; OS: HR = 5.3615, 95% CI: 1.1014–26.099, P = 0.0376). The IC50 (half maximal inhibitory concentration) of Crenolanib of CN-AML samples with RASGEF1A high expression level is lower. In addition, patients with high RASGEF1A methylation level had significant favorable prognosis (EPS: P < 0.0001, OS: P < 0.0001). Furthermore, the integrative analysis of expression and methylation of RASGEF1A could classify CN-AML patients into subgroups with different prognosis (EFS: P = 0.034, OS: P = 0.0024). Expression levels or methylation levels of RASGEF1A help to improve risk classification of 2010 European Leukemia Net. CONCLUSION: Higher RASGEF1A RNA expression and lower DNA methylation predicts CN-AML patients' poorer prognosis. The RASGEF1A high expression level from patients with CN-AML have better sensitivity to Crenolanib. The integrative analysis of RASGEF1A RNA expression and DNA methylation can provide a more accurate classification for prognosis. Lower RASGEF1A expression is a favorable prognostic factor for AML patients receiving chemotherapy or Allo-HSCT. 2010 European Leukemia Net's risk classification can be improved by RASGEF1A expression levels or methylation levels. [ABSTRACT FROM AUTHOR]

eIF3a is the largest subunit of eIF3, which is a key player in all steps of translation initiation. During the past years, eIF3a is recognized as a proto-oncogene, which is an important discovery in this field. It is widely reported to be correlated with cancer occurrence, metastasis, prognosis, and therapeutic response. Recently, the mechanisms of eIF3a action in the carcinogenesis are unveiled gradually. A number of cellular, physiological, and pathological processes involving eIF3a are identified. Most importantly, it is emerging as a new potential drug target in the eIF family, and some small molecule inhibitors are being developed. Thus, we perform a critical review of recent advances in understanding eIF3a physiological and pathological functions, with specific focus on its role in cancer and anticancer drug targets. [ABSTRACT FROM AUTHOR]

Background Cluster of differentiation 47 (CD47) negatively regulates macrophage phagocytosis and is correlated with adverse survival of multiple cancers. In melanoma patients, especially in Chinese melanoma patients, its prognostic value is unclear. In this study, we aim to study the prognostic value of CD47 in a Chinse melanoma patient cohort and its immunomodulation roles in mouse model. Method 164 melanoma tissue specimens were collected. The expression of CD47 in these clinical samples was examined by immunohistochemistry staining (IHC). The correlation between CD47 expression and clinicopathological parameters was assessed by statistical analysis. Prognostic values CD47 expression were also investigated. In an animal model, effects of CD47 expression on immune infiltration were examined. Results CD47 expression was positively correlated with TNM stage, distant metastasis, and death of melanoma patients with the P value of 0.008, 0.018, and 0.032 respectively. High expression of CD47 was an independent prognostic marker of overall survival (HR = 1.563, 95% CI: 1.069–2.285) and progression free survival (HR = 1.542, 95% CI: 1.053–2.258) of Chinese melanoma patients. Conclusion In conclusion, high expression of CD47 predicted poor survival in a Chinese melanoma patient cohort and impaired antitumor immune response in the animal model. Targeting CD47 might be a novel option for melanoma patients. [ABSTRACT FROM AUTHOR]

poorly cohesive (PC) gastric cancer (GC) (PC-GC) is a distinct histological subtype of GC and is defined as a tumor consisting of isolated or small clusters of tumor cells with poorly differentiated and metastatic characteristics. According to multiple studies, PC-GC is intrinsically heterogeneous, with mesenchymal variants being the most aggressive. However, to date, the molecular mechanisms associated with PC-GC are still not fully understood. This study investigated the role of the USP51/ZEB1/ACTA2 axis in promoting GC metastasis. Single-cell sequencing revealed that E-box binding homeobox 1 (ZEB1) expression was significantly increased in a subpopulation of low-adherent cells and was an independent prognostic factor in GC patients. Furthermore, the bulk transcriptome analysis revealed a significant positive correlation between Ubiquitin Specific Peptidase 51 (USP51), ZEB1, and Actin Alpha 2 (ACTA2), and our data further confirmed that all three were highly co-localized in PC-GC tissues. According to the findings of in vitro and in vivo experiments, USP51 was able to maintain ZEB1 expression to promote ACTA2 transcription, thereby activating the mesenchymal phenotype of GC cells and promoting tumor metastasis. Moreover, USP51 could recruit and activate stromal cells, including M2-like macrophages and fibroblasts, through cancer cells. Clinical data suggested that overexpression of USP51 predicts that patients have difficulty benefiting from immunotherapy and is associated with immune-exclusion tumor characteristics. Collectively, the findings of this study shed light on a key mechanism by which elevated USP51 expression induces Epithelial-mesenchymal transition (EMT) in GC cells, hence facilitating GC cell proliferation, survival, and dissemination. In this view, USP51/ZEB1/ACTA2 may serve as a candidate therapeutic target against GC metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Small cell lung cancer (SCLC) is the most malignant and common form of neuroendocrine lung cancer with pure (P‐SCLC) and combined subtypes (C‐SCLC). However, little is known about the differences between these two groups and in this study we aimed to provide a more comprehensive insight into SCLC. Methods: Data from 580 postoperative patients with pathologically confirmed SCLC in Shanghai Chest Hospital from January 2010 to December 2020 were collected retrospectively. The clinical characteristics and prognosis were analyzed. Results: A total of 357 P‐SCLC patients and 223 C‐SCLC patients were included. The results indicated that P‐SCLC appeared to have a higher proportion of being located in the middle lobe than C‐SCLC. The incidences of P‐SCLC in patients with visceral pleural invasion (VPI) and in stage II were higher than C‐SCLC, while C‐SCLC was more likely to be accompanied by higher incidences of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) rearrangement, and higher levels of CEA, SCCA and CYFRA21‐1 than P‐SCLC. The most common were SCLC combined with large cell neuroendocrine components among 223 C‐SCLCs. Survival analysis confirmed a more favorable disease‐free survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.024) in patients with P‐SCLCs compared with C‐SCLCs. Histological type, tumor location, pN stage, adjuvant chemotherapy, serum NSE and CA125 levels were independent risk factors for survival rate in SCLC. In addition, adjuvant chemotherapy was beneficial in improving stage I P‐SCLC and C‐SCLC DFS and OS rates, and similar results were not seen in adjuvant radiation therapy. Conclusions: Patients with C‐SCLC have a poorer prognosis than P‐SCLC patients. We determined that large cell neuroendocrine carcinoma was the most common additional component of C‐SCLC, and patients with this component appeared to have a longer DFS and OS than other combined components. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore predictors and construct a nomogram for risk stratification in primary extragastric mucosa‐associated lymphoid tissue (MALT) lymphoma. Methods: Extragastric MALT lymphoma cases newly diagnosed between November 2010 and April 2020 were assessed to construct a progression‐free survival (PFS)‐related nomogram. We also performed external validation of the nomogram in an independent cohort. Results: We performed multivariate analyses of 174 patients from 3 hospitals who were included in the training cohort. Stage, hepatitis B virus surface antigen (HBsAg) status, and Ki67 expression were significantly associated with PFS. These three factors were used to construct a nomogram, which was shown to have a C‐index of 0.89. Two risk groups (low risk and high risk) were identified by the prognostic model. The 5‐year PFS was 98.9% for the low‐risk group and 69.3% for the high‐risk group (p < 0.001). The overall survival (OS) could also be effectively distinguished by the nomogram, resulting in an OS of 100% for the low‐risk group and 94.6% for the high‐risk group (p = 0.01). These results were validated and confirmed in an independent cohort with 165 patients from another three hospitals. The 5‐year PFS rates were 94.8% and 66.7% for the low‐risk and high‐risk groups, respectively (p < 0.001). The 5‐year OS rates were 97.9% and 88.4%, respectively (p = 0.016). Conclusion: The nomogram could well distinguish the prognosis of low‐ and high‐risk patients with extragastric MALT lymphoma and is thus recommended for clinical use. [ABSTRACT FROM AUTHOR]

• Accurate prognostic prediction for head and neck cancer is important for clinics. • Compared with the traditional Cox regression algorithm, machine learning techniques can reflect the nonlinear associations that exist in clinical practice. • Among the machine learning techniques, random forest performs best in survival predictions of Head and Neck cancer. Accurate prognostic prediction for head and neck cancer (HNC) is important for the improvement of clinical management. We aimed to compare the prognostic value of various machine learning techniques (MLTs) and statistical Cox regression model for different types of HNC. Clinical data of HNC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 1974 to 2016. The prediction performance of five ML models, including random forest (RF), gradient boosting decision tree (GBDT), support vector machine (SVM), neural network (NN) and deep learning (DL), were compared with the statistical Cox regression model by estimating the concordance index (C-index), integrated Brier score (IBS), time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC). Our results showed that the RF model outperformed all other models in prognostic prediction for all tumor sites of HNC, particularly for major salivary gland cancer (MSGC, C-index: 88.730 ± 0.8700, IBS: 7.680 ± 0.4800), oral cavity cancer (OCC, C-index: 84.250 ± 0.6700, IBS: 11.480 ± 0.3300) and oropharyngeal cancer (OPC, C-index: 82.510 ± 0.5400, IBS: 10.120 ± 0.1400). Meanwhile, we analyzed the importance of each clinical variable in the RF model, in which age and tumor size presented the strongest positive prognostic effects. Additionally, similar results can be observed in the internal (6th edition of the AJCC TNM staging system cohort) and external validations (the TCGA HNC cohort). The RF model is a promising prognostic prediction tool for HNC patients, regardless of the anatomic subsites. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes (TILs), investigated using routine hematoxylin and eosin (H&E)-stained section slides (H&E-sTILs), provide a robust prognostic biomarker in various types of solid cancer. The purpose of the present study was to investigate the prognostic significance of H&E-sTILs in patients with small cell lung cancer (SCLC). Methods: The clinical data of patients with SCLC who had been treated in our cancer center between January 2013 and October 2019 were collected and retrospectively reviewed. The H&E-sTILs were re-assessed by two experienced pathologists independently. H&E-sTILs that affected the overall survival (OS), progression free survival (PFS) and brain-metastasis free survival (BMFS) rates were explored using the Kaplan–Meier method, and the log-rank test was used to assess the differences. Multivariate analysis was subsequently performed using the Cox proportion hazards model. Results: A total of 159 patients with SCLC who fulfilled the inclusion criteria were enrolled in the current study. The OS rates at 1, 2 and 3 years were 59.8, 28.6 and 19.8%, respectively, for the whole group. The 3-year OS, PFS and BMFS rates for the H&E-sTILs(+) and H&E-sTILs(−) groups were 25.1% cf. 5.1% (P = 0.030), 14.0% cf. 4.0% (P = 0.013), and 66.0% cf. 11.4% (P = 0.023), respectively. Multivariate analyses subsequently revealed that H&E-sTILs, clinical M stage, the cycles of chemotherapy and short-term response to thoracic radiotherapy were independent factors affecting OS, whereas H&E-sTILs, clinical N stage, clinical M stage and short-term response to chemotherapy were factors affecting PFS. The H&E-sTILs affected OS, PFS and BMFS simultaneously. Conclusions: The results of this retrospective study have shown that H&E-sTILs may be considered as a prognostic biomarker affecting the short-term response to treatment, and they are the one and only risk factor for BMFS. However, due to the limitations of the nature of the retrospective design and shortcomings in visually assessing the TILs based on the H&E-stained slides, further prospective studies are required to confirm these conclusions. [ABSTRACT FROM AUTHOR]

• For the first time, established a predictive model to anticipate the cytokine storms in the acute phase of SFTS patients. • By visualizing the predictive model through a nomogram, it becomes more convenient and user-friendly. • The predictive capacity of the model was evaluated based on the outcomes of 48 cytokines in the validation cohort. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients. [ABSTRACT FROM AUTHOR]

The pathogenesis and progression of follicular lymphoma (FL) depends on immune evasion mechanisms. The gut microbiota has been reported to be associated with the development and outcome of several human diseases by modulating host immunity. Thus, the present study investigated the characteristics and prognostic value of the gut microbiota in FL. Fecal samples from treatment-naïve patients with FL (n=28) and healthy controls (n=18) were prospectively collected. The gut microbiota diversity and composition were examined by 16S ribosomal RNA sequencing. The results demonstrated that patients with FL had distinct microbiota compositions. The relative abundance of the Ruminococcaceae family was significantly increased in patients with FL (P=0.01). Furthermore, a high level of Ruminococcus was identified as a strong indicator of tumor burden (P=0.001), and was related to the FL International Prognostic Index score and serum lactate dehydrogenase levels. The present results indicated an association between the gut microbiota and FL prognosis. Findings from the present study may provide a rational foundation for further investigation of the role of gut microbiota in lymphoma management. [ABSTRACT FROM AUTHOR]

The contribution of diabetes to breast cancer remains uncertain among Chinese females, which may result from different genetic factors. We evaluated the associations of diabetes, combined with the polymorphisms in the genes of fat mass and obesity-associated gene (FTO), interleukin 6 (IL-6), and heat shock protein 60 (HSPD1), with breast cancer risk and survival in a Chinese Han population. The information on the history of diabetes was collected from 1551 incident breast cancer cases and 1605 age-frequency matched controls in Guangzhou, China. In total, 1168 cases were followed up. Diabetes was associated with both an increased risk of breast cancer [OR (95%CI): 1.67 (1.11, 2.52)] and a poor overall survival and progression free survival for breast cancer patients [HRs (95%CIs): 2.66 (1.10, 6.44) and 2.46 (1.29, 4.70), respectively]. IL-6 rs1800796 and HSPD1 rs2605039 had interactions with diabetes on breast cancer risk. Among women with CC genotype of IL-6 rs1800796 or GG genotype of HSPD1 rs2605039, diabetic individuals had a remarkably increased risk of breast cancer compared to non-diabetic women with ORs and 95%CIs of 2.53 (1.45, 4.41) and 6.40 (2.29, 17.87), respectively. GT/TT genotypes of HSPD1 rs2605039 was also associated with a better progression free survival for breast cancer patients [HR (95%CI): 0.70 (0.49, 0.99)]. Our results suggest that the contribution of diabetes to breast cancer risk might be modified by IL-6 rs1800796 and HSPD1 rs2605039. Diabetes and HSPD1 rs2605039 might also influence breast cancer prognosis. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes (TILs), investigated using routine hematoxylin and eosin (H&E)-stained section slides (H&E-sTILs), provide a robust prognostic biomarker in various types of solid cancer. The purpose of the present study was to investigate the prognostic significance of H&E-sTILs in patients with small cell lung cancer (SCLC).Methods: The clinical data of patients with SCLC who had been treated in our cancer center between January 2013 and October 2019 were collected and retrospectively reviewed. The H&E-sTILs were re-assessed by two experienced pathologists independently. H&E-sTILs that affected the overall survival (OS), progression free survival (PFS) and brain-metastasis free survival (BMFS) rates were explored using the Kaplan-Meier method, and the log-rank test was used to assess the differences. Multivariate analysis was subsequently performed using the Cox proportion hazards model.Results: A total of 159 patients with SCLC who fulfilled the inclusion criteria were enrolled in the current study. The OS rates at 1, 2 and 3 years were 59.8, 28.6 and 19.8%, respectively, for the whole group. The 3-year OS, PFS and BMFS rates for the H&E-sTILs(+) and H&E-sTILs(-) groups were 25.1% cf. 5.1% (P = 0.030), 14.0% cf. 4.0% (P = 0.013), and 66.0% cf. 11.4% (P = 0.023), respectively. Multivariate analyses subsequently revealed that H&E-sTILs, clinical M stage, the cycles of chemotherapy and short-term response to thoracic radiotherapy were independent factors affecting OS, whereas H&E-sTILs, clinical N stage, clinical M stage and short-term response to chemotherapy were factors affecting PFS. The H&E-sTILs affected OS, PFS and BMFS simultaneously.Conclusions: The results of this retrospective study have shown that H&E-sTILs may be considered as a prognostic biomarker affecting the short-term response to treatment, and they are the one and only risk factor for BMFS. However, due to the limitations of the nature of the retrospective design and shortcomings in visually assessing the TILs based on the H&E-stained slides, further prospective studies are required to confirm these conclusions. [ABSTRACT FROM AUTHOR]