Search

Objective: Polo‐like kinase 1 (PLK1), a serine/threonine‐protein kinase, functions as a potent oncogene in the initiation and progression of tumor. The aim of this study is to assess potential correlations between PLK1 expression and immune infiltration in breast cancer (BRCA) and construct a PLK1‐based immune risk model applicable for prognosis and treatment response prediction in BRCA. Methods: We collected data on PLK1 gene expression in BRCA patients from The Cancer Genome Atlas (TCGA) database. Thereafter, we analyzed the associations of PLK1 expression with immune cell infiltration and immunomodulators, and established a prognostic risk model based on seven PLK1‐associated immunomodulator genes and a nomogram for survival prediction. Results: BRCA prognosis, clinical stage progression, and tumor classification were all shown to be substantially correlated with PLK1 expression. The PLK1 gene was significantly enriched in T cell and B cell receptors and molecules of the chemokine signaling pathways. Specifically, PLK1 expression was positively correlated with the CD8+ T cell and regulatory T cell (Tregs) activation and negatively correlated with M2 macrophage infiltration. The seven‐genes‐based risk model could serve as an independent prognostic factor of BRCA. The risk model was markedly correlated with the expression of programmed cell death protein 1/programmed cell death ligand 1 (PD‐1/PD‐L1; both p < 0.001) immune checkpoints, and tumor mutation burden (TMB). High‐ and low‐risk BRCA patients identified by the risk model responded differently to anti‐PD‐1 and/or anti‐CTLA4 therapy, as well as common chemotherapy drugs, like cisplatin, paclitaxel, and gemcitabine. Conclusion: This PLK1‐based immune risk model can effectively predict the prognosis and tumor progression of BRCA, identify gene mutations, and evaluate patient's response toward immunotherapy and chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Purpose: Keratin 18 (KRT18) is a cytoskeleton protein that plays a key role in multiple cancers. The present study aims to further investigate the roles of KRT18 in gastric cancer (GC) tissues and cells. Methods: The KRT18 protein expression levels of GC tissues and cells were detected using immunohistochemistry and western blot. The relationship between KRT18 expression levels and the prognosis of GC patients was further analyzed. To explore this relationship, small interfering RNA (siRNA) was used to inhibit the endogenous expression of KRT18 in GC cells. Furthermore, the effects of KRT18 on the proliferation, invasion, migration, and apoptosis of GC cells were analyzed in vitro. In addition, the role of KRT18 in GC‐specific processes was investigated. Results: Keratin 18 expression was shown to be up‐regulated in GC tissues and associated with poor prognosis. Following KRT18 silencing with siRNA, the proliferation, invasion, and migration ability of GC cells were significantly inhibited, while the apoptotic process was promoted. Furthermore, the activation of the MAPK signalling pathway was identified as the potential mechanism through which KRT18 influenced GC processes. Conclusions: Keratin 18 plays a cancer‐promoting role and might be a potential therapeutic target in the treatment of GC. [ABSTRACT FROM AUTHOR]

Purpose: Transcription co‐activator p300/CBP, a histone acetyltransferase, has a central role in tumours, inflammation and neurodegenerative diseases. We investigated the effect of p300/CBP and its association with various IL‐17‐related indicators and prognosis in patients with acute respiratory distress syndrome (ARDS). Materials and Methods: We enrolled 45 adult ARDS patients who were followed for 28 days and 22 healthy controls. The mRNA expression of p300, CBP, RORγt and Foxp3 and the plasma levels of several cytokines were measured. Result: The mRNA levels of p300, CBP and RORγt, and plasma concentration of IL‐17, IL‐6, were higher in acute ARDS patients (P < 0.05) compared with controls, and the mean levels of p300, CBP and IL‐6 in non‐survivors were higher than in survivors (P < 0.05). The expression of p300 was associated with the level of RORγt, IL‐17 and disease prognosis. Conclusion: The levels of p300, RORγt mRNA and plasma concentration of IL‐6 and IL‐17 in acute ARDS patients were increased compared with controls. Increased p300/CBP expression may be an independent risk factor for 28‐day mortality in ARDS. [ABSTRACT FROM AUTHOR]

Aim Selecting pathologic measures of placental inflammation that affect pregnancy and childhood health is largely empirical. We aimed to systematically select several core inflammation-related placental measures to construct a novel placental inflammatory evaluation criterion with a high prognostic relevance to child morbidity. Methods We used data from the US Collaborative Perinatal Project (1959-1976), a longitudinal birth cohort study that recruited women during pregnancy and followed the children until 7 years of age. Bootstrap resampling, least absolute shrinkage and selection operator, and receiver-operator curve were used to select placental pathologic measures that were closely related to child morbidity to form a placental inflammatory composite index. Results Twenty-six candidate placental inflammation-related measures were ranked based on their close association with adverse neonatal outcomes. The top five placental measures were: (i) neutrophilic infiltration in umbilical artery; (ii) placental weight-birthweight ratio; (iii) necrosis in decidua capsularis; (iv) bacterial colony in epithelium of amnion; and (v) opacity of membranes and fetal surface. Several composite indexes were constructed. A five-measure composite index that had the highest prognostic relevance was chosen. Compared with subjects without any of the five abnormal measures, those with any lesion ranging from 1 to 5 had a 1.2- to 4.6-fold risk of adverse child outcomes, respectively. Conclusion Our composite index is simple, evidence-based, and has predictive value for child morbidity. It may be used as a novel placental inflammatory evaluation criterion. [ABSTRACT FROM AUTHOR]

Objective: To compare postoperative CT images with plain radiographs for measuring prognostic factors of reduction loss of fractures of the proximal part of the humerus. Methods: A total of 65 patients who sustained fractures of the proximal humerus treated with locking plates from June 2012 to October 2015 were retrospectively analyzed. There were 24 men and 41 women, with a mean age of 60.0 years (range, 22-76 years). According to the Neer classification system of proximal humeral fracture, there were 26 two-part, 27 three-part and 12 four-part fractures of the proximal part of the humerus, and all fractures were treated with open reduction and internal fixation (ORIF) using locked plating. All postoperative CT images and plain radiographs of the patients were obtained. Prognostic factors of the reduction loss were the change of neck shaft angle (NSA) and the change of humeral head height (HHH). The change of NSA and HHH were evaluated by the difference between postoperative initial and final follow-up measurement. Reduction loss was defined as the change ≥10° for NSA or ≥5 mm for HHH. The NSA and HHH were measured using plain radiographs and 3-D CT images, both initially and at final follow-up. The paired t-test was used for comparison of NSA, change of NSA, HHH, and change of HHH between two image modalities. The differences between two image modalities in the assessment of reduction loss were examined using the ?2-test (McNemar test). Intraclass correlation coefficients (ICC) were used to assess the intra-observer and inter-observer reliability. Results: 3-D CT images (ICC range, 0.834-0.967) were more reliable in all parameters when compared with plain radiographs (ICC range, 0.598-0.915). Significant differences were found between the two image modalities in all parameters (plain radiographs: initial NSA = 133.6° ± 3.8°, final NSA = 130.0° ± 1.9°, initial HHH = 17.9 ± 0.9 mm, final HHH = 15.8 ± 1.5 mm; 3-D CT: initial NSA = 131.4° ± 3.4°, final NSA = 128.8° ± 1.7°, initial HHH = 16.8 ± 1.2 mm, final HHH = 14.5 ± 1.1 mm; all P < 0.05). In the assessment of reduction loss, the percentage was 16.9% (11/65) for the plain radiographs and 7.7% (5/65) for the 3-D CT scans (P < 0.05). For the 5 patients with reduction loss, which were observed by two imaging modalities, the mean Constant-Murley score was 61.0 ± 1.6. The patients with reduction loss, observed only in plain radiographs but not CT images, had good shoulder function (Constant-Murley score: 82.7 ± 1.0). Conclusions: Our data reveal that 3-D CT images are more reliable than plain radiographs in the assessment of the prognostic factors of reduction loss of fractures of the proximal part of the humerus with treatment of locking plates; this reliable CT technique can serve as an effective guideline for the subsequent clinical management of patients. [ABSTRACT FROM AUTHOR]

Background and Aim: MicroRNA-18a (miR-18a) has been reported to be upregulated in gastric cancer (GC) tissues compared with normal gastric tissues. However, little is known about its prognostic value and biological roles. Methods: In this study, miR-18a expression in gastric adenocarcinoma (GAC) tissues and adjacent non-tumor tissues was validated by in situ hybridization, and the predictive values of miR-18a were explored. The biological roles of miR-18a and the underlying signal pathway were investigated in GC cell lines. Results: Overexpressed intra-tumoral miR-18a was associated with poor survival rate and was an independent prognostic factor for overall survival rate ( P < 0.001) in GC patients. Forced expression of miR-18a remarkably enhanced cell proliferation, migration, and invasion in GC cells, while inhibition of miR-18a caused the opposite effects. Further study showed that miR-18a suppressed the expression of interferon regulatory factor 2 (IRF2) by directly binding to its 3′-untranslated region. Moreover, miR-18a expression levels are inversely correlated with IRF2 in human GC tissues. Western blot showed that forced expression of miR-18a could not only downregulate the expression of IRF2, but also inhibit the expression of P53, suggesting that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC. Conclusion: miR-18a modulated P53 expression by directly targeting IRF2 and had a high predictive value for prognosis of GAC patients. These results may lead to identification of therapeutic candidates of GC. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood‐based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. Methods: A three‐phase multicentre study was conducted to screen, optimise and validate HCC‐specific differentially methylated regions (DMRs) using next‐generation sequencing and quantitative methylation‐specific PCR (qMSP). Results: Genome‐wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre‐ and postoperative plasma samples from 103 HCC patients and correlated with 2‐year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p <.001). Conclusions: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC‐specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at‐risk populations. [ABSTRACT FROM AUTHOR]

Aim: To clarify the role of Eomesodermin (EOMES) to serve as a disease‐relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4+T subsets in amyotrophic lateral sclerosis (ALS). Methods: The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T‐cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1‐year longitudinal follow‐ups, the ALSFRS‐R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort. Results: In the derivation cohort, the CD4+EOMES+T‐cell subsets were significantly increased (p < 0.001). EOMES+ subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4+EOMES+T‐cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (p =.010) and worse prognosis (p =.003). Conclusions: We demonstrated that increased CD4+EOMES+T‐cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS. [ABSTRACT FROM AUTHOR]

Background and Aim: The spatial distribution and interactions of cells in the tumor immune microenvironment (TIME) might be related to the different responses of triple‐negative breast cancer (TNBC) to immunomodulators. The potential of multiplex IHC (m‐IHC) in evaluating the TIME has been reported, but the efficacy is insufficient. We aimed to research whether m‐IHC results could be used to reflect the TIME, and thus to predict prognosis and complement the TNBC subtyping system. Methods: The clinical, imaging, and prognosis data for 86 TNBC patients were retrospectively reviewed. CD3, CD4, CD8, Foxp3, PD‐L1, and Pan‐CK markers were stained by m‐IHC. Particular cell spatial distributions and interactions in the TIME were evaluated with the HALO multispectral analysis platform. Then, we calculated the prognostic value of components of the TIME and their correlations with TNBC transcriptomic subtypes and MRI radiomic features reflecting TNBC subtypes. Results: The components of the TIME score were established by m‐IHC and demonstrated positive prognostic value for TNBC (p = 0.0047, 0.039, <0.0001 for DMFS, RFS, and OS). The score was calculated from several indicators, including Treg% in the tumor core (TC) or stromal area (SA), PD‐L1+ cell% in the SA, CD3 + cell% in the TC, and PD‐L1+/CD8+ cells in the invasive margin and SA. According to the TNBC subtyping system, a few TIME indicators were significantly different in different subtypes and significantly correlated with MRI radiomic features reflecting TNBC subtypes. Conclusion: We demonstrated that the m‐IHC‐based quantitative score and indicators related to the spatial distribution and interactions of cells in the TIME can aid in the accurate diagnosis of TNBC in terms of prognosis and classification. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to identify prognostic autophagy‐related genes and assess the ability of these genes to predict clinical outcomes in oral squamous cell carcinoma (OSCC). Subjects and methods: The details of the human autophagy‐related genes were obtained from the Human Autophagy Database. The Cancer Genome Atlas database was used to obtain the gene expression profiles and clinical data of patients. Prediction of biological functions of differentially expressed genes was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Prognosis‐related genes were identified by Cox regression analysis, and the coefficient was applied to construct a prognostic risk score model. The median of the risk score was applied to distinguish between high‐ and low‐risk groups. The Gene Expression Omnibus database, qRT‐PCR and immunohistochemistry were used to validate the expression of key genes. Results: KEGG analyses revealed that differentially expressed genes were mainly enriched in autophagy‐related pathways and virus infection. BAK1, BID, NKX2‐3 and SPHK1 were identified. The risk score model showed that the high‐risk score had poorer overall survival (Kaplan‐Meier analysis, p = 1.79 × 10–7). SPHK1 was upregulated in OSCC tissues and cells, and NXK2‐3 was downregulated. Conclusions: Autophagy‐related gene expression profiles may be a potential biomarker for OSCC prognosis. [ABSTRACT FROM AUTHOR]

Background: Stress hyperglycemia ratio (SHR), a novel biomarker of stress hyperglycemia, was proved to be a reliable predictor of short‐term adverse outcomes in patients with acute coronary syndromes (ACS). However, its impact on long‐term prognosis remained controversial. Methods: A total of 7662 patients with ACS from a large nationwide prospective cohort between January 2015 and May 2019 were included. SHR was calculated by the following formula: SHR = admission glucose (mmol/L)/(1.59 × HbA1c [%]−2.59). The primary end point was a major adverse cardiovascular event (MACE) during follow‐up, a composite of all‐cause death, myocardial infarction, and unplanned revascularization. The second end point was the separate components of the primary end points. Results: During a median follow‐up of 2.1 years, 779 MACE events occurred. After multivariable adjustment, ACS patients with the highest SHR tertile were significantly associated with increased long‐term risks of MACE (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.24–1.88), all‐cause death (HR 1.80, 95% CI 1.29–2.51) and unplanned revascularization (HR 1.44, 95% CI 1.09–1.91). Although significant associations between the highest SHR tertile and risks of MACE and all‐cause death were assessed in both diabetic and nondiabetic patients, the patterns of risk were different in these two groups. Conclusion: Elevated SHR was independently associated with a higher risk of long‐term outcomes irrespective of diabetic status, suggesting that SHR was a potential biomarker for risk stratification after ACS. [ABSTRACT FROM AUTHOR]

Crohn's disease is a recurrent, progressive, immune‐mediated inflammatory disease and merely manifests non‐specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT‐PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR‐582‐5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606–0.796, p <.001). While PBMC miR‐96‐5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p <.001) and endoscopic activity (ρ = 0.512, p =.015). Furthermore, PBMC miR‐96‐5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609–0.844, p =.001) than C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR‐582‐5p may be further utilized as a diagnostic biomarker, while miR‐96‐5p may be a novel and valuable biomarker in monitoring disease activity. [ABSTRACT FROM AUTHOR]

Background and objective: The pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize patients with acute pulmonary thromboembolism (PTE) with low prognosis risk, which is of great significance for treatment. This study aims to verify the influence of hypocalcaemia on the prognosis of patients with PTE and to establish a new prognosis assessment model. Methods: This is an observational, multicentre study enrolling patients with PTE from February 2010 to June 2020 across 12 Chinese hospitals. Variables in PESI, serum calcium levels and patient survival status as of 5 July 2020 were collected. The area under the curve of the receiver operating characteristic curve, sensitivity, specificity and Youden index were used to evaluate model performance. Results: In the cohort of 4196 patients with PTE, independent associations existed between hypocalcaemia and mid‐ and long‐term mortalities (p <0.05). By including hypocalcaemia, the new 30‐day death risk prediction rule, Peking Union Medical College Hospital rule (PUMCH rule), showed significantly higher specificity (0.622 [0.582, 0.661]; p <0.001) than the PESI (0.514 [0.473, 0.554]) and sPESI (0.484 [0.444, 0.525]) and similar sensitivity (0.963 [0.810, 0.999]; p = 0.161) with PESI (0.889 [0.708, 0.976]) and sPESI (0.963 [0.810, 0.999]) in the internal validation cohort. Well‐performing predictive validity was also verified on a constructed external validation cohort. Conclusion: Hypocalcaemia is independently associated with mid‐ and long‐term PTE mortalities. The PUMCH rule showed significantly higher specificity than the PESI and sPESI and similar sensitivity, which may be used as a prognostic assessment tool for patients with acute PTE. Currently, pulmonary embolism severity index (PESI) and simplified PESI (sPESI) are recommended to recognize pulmonary thromboembolism (PTE) patients with low prognosis risk. In this multicentre research, a new prognosis assessment model including hypocalcaemia, which is confirmed to be independently associated with mid‐ and long‐term PTE mortalities, showed significantly higher specificity with PESI and sPESI and similar sensitivity. See relatedEditorial [ABSTRACT FROM AUTHOR]

Background: Numerous reports on microRNAs have illustrated their role in tumor growth and metastasis. Recently, a new prognostic factor, miR‐125b‐2‐3p, has been identified for predicting chemotherapeutic sensitivity in advanced colorectal cancer (CRC). However, the specific mechanisms and biological functions of miR‐125b‐2‐3p in advanced CRC under chemotherapy have yet to be elucidated. Methods: MiR‐125b‐2‐3p expression was detected by real‐time PCR (RT‐PCR) in CRC tissues. The effects of miR‐125b‐2‐3p on the growth, metastasis, and drug sensitivity of CRC cells were tested in vitro and in vivo. Based on multiple databases, the upstream competitive endogenous RNAs (ceRNAs) and the downstream genes for miR‐125b‐2‐3p were predicted by bioinformatic analysis, followed by the experiments including luciferase reporter assays, western blot assays, and so on. Results: MiR‐125b‐2‐3p was significantly lowly expressed in the tissues and cell lines of CRC. Higher expression of miR‐125b‐2‐3p was associated with relatively lower proliferation rates and fewer metastases. Moreover, overexpressed miR‐125b‐2‐3p remarkably improved chemotherapeutic sensitivity of CRC in vivo and in vitro. Mechanistically, miR‐125b‐2‐3p was absorbed by long noncoding RNA (lncRNA) XIST regulating WEE1 G2 checkpoint kinase (WEE1) expression. The upregulation of miR‐125b‐2‐3p inhibited the proliferation and epithelial‐mesenchymal transition (EMT) of CRC induced by lncRNA XIST. Conclusions: Lower miR‐125b‐2‐3p expression resulted in lower sensitivity of CRC to chemotherapy and was correlated with poorer survival of CRC patients. LncRNA XIST promoted CRC metastasis acting as a ceRNA for miR‐125b‐2‐3p to mediate WEE1 expression. LncRNA XIST‐miR‐125b‐2‐3p‐WEE1 axis not only regulated CRC growth and metastasis but also contributed to chemotherapeutic resistance to CRC. [ABSTRACT FROM AUTHOR]

Background: Poor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS).Methods: The CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed.Results: Among 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5]).Conclusions: Stroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer. [ABSTRACT FROM AUTHOR]

The receptor‐tyrosine‐kinase (RTK)‐like orphan receptor 1 (ROR1) is a transmembrane glycoprotein regarded as a tumor‐associated antigen. ROR1 plays an important role in cancer development, but the detailed function of ROR1 in diffuse large B‐cell lymphoma (DLBCL) remains unclear. In this study, we first detected ROR1 expression and evaluated the relationship between ROR1 expression and the clinicopathological characteristics of DLBCL patients. Next we employed shRNA‐mediated knockdown of ROR1 in DLBCL cell line to explore the characteristics of ROR1 in DLBCL development both in vitro and in vivo. The results showed a significantly higher level of ROR1 in DLBCL tissues than in lymphatic hyperplasia tissues. High ROR1 expression was correlated with unfavorable prognosis in DLBCL patients. Furthermore, ROR1 knockdown inhibited the growth and induced the apoptosis in DLBCL cells and xenografts. In addition, shROR1 inhibited activation of the PI3K/Akt/mTOR signaling pathway, both in vitro and in vivo. Taken together, our results suggest that ROR1 is a novel prognostic marker for DLBCL survival and ROR1 significantly promotes DLBCL tumorigenesis by regulating the PI3K/Akt/mTOR signaling pathway. Targeting ROR1 may provide a promising strategy for DLBCL treatment. © 2019 BioFactors, 45(3):416–426, 2019 [ABSTRACT FROM AUTHOR]

Purpose: Tissue carcinoembryonic antigen (t‐CEA) and serum carcinoembryonic antigen (s‐CEA) expression profiles are the most useful tumor markers for the diagnosis and evaluation of colorectal cancer (CRC) worldwide; however, their roles in CRC progression remain controversial. This study aimed to compare the prognostic values of both s‐CEA and t‐CEA in CRC. Methods: A total of 517 patients from January 2006 to December 2010 with stages I‐III CRC were retrospectively examined, with 5‐year postoperative follow‐up and death as end‐points. T‐CEA expression, s‐CEA expression, and clinical pathological parameters were inputted into the SPSS 21.0 software. The Kaplan‐Meier method was used to analyze the 5‐year disease‐free survival (DFS) rate of patients in different tumor node metastasis (TNM) stages based on t‐CEA and s‐CEA expression. Results: Tumor differentiation and the number of positive lymph node harvests were significantly different among the t‐CEA groups (P < 0.001, P = 0.002); however, clinicopathological features showed no significant difference. The groups with high s‐CEA and t‐CEA expression had a significantly poorer prognosis than those with low s‐CEA (P = 0.021) and t‐CEA (P < 0.01) expression, respectively. The multivariate analysis demonstrated that t‐CEA was an independent prognostic factor in CRC (P < 0.001), but s‐CEA was not (P = 0.339). The 5‐year disease‐free survival rates among the t‐CEA groups were significantly different in stages I, II, and III of CRC (P = 0.001, P < 0.001, P < 0.001), whereas in the s‐CEA groups, this difference was observed only in stage III (P = 0.014). Conclusion: This study shows that postoperative t‐CEA expression is an independent factor associated with poorer CRC prognosis and has a higher prognostic value than that of preoperative s‐CEA expression. Tissue carcinoembryonic antigen (t‐CEA)expression and serum carcinoembryonic antigen (s‐CEA) expression of colorectal carcinoma (CRC) are the most useful tumor markers for the diagnosis and evaluation of prognosis, but the role remains controversial. The objective of this study was to compare the prognostic value of CEA both in serum and tumor tissue in CRC. [ABSTRACT FROM AUTHOR]

Aims To examine, in nasopharyngeal carcinoma ( NPC), the correlation of Krüppel-like factor 4 ( KLF4) expression with clinicopathological features including patient prognosis. Methods and results Using real-time PCR and immunohistochemistry, expression of KLF4 m RNA and protein was examined in NPC and nasopharyngeal tissues. The relationship of KLF4 expression levels with clinical features and prognosis of NPC patients was analysed. m RNA expression was markedly lower in NPC than in the nasopharyngeal tissues. Using immunohistochemistry, staining for KLF4 protein was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells, but decreased cytoplasmic expression was observed in atypical hyperplasia and NPC samples compared to normal and squamous epithelium samples ( P < 0.001). In addition, levels of cytoplasmic KLF4 protein were correlated inversely with the nodal (N) status (T NM classification; P = 0.002) and overall clinical stage ( P < 0.001) of NPC patients. Patients with NPC showing lower cytoplasmic KLF4 expression had a significantly shorter overall survival time than those with high NPC KLF4 expression. Multivariate analysis suggested that the level of KLF4 expression was an independent prognostic indicator ( P = 0.008) for NPC survival. Conclusion Low levels of cytoplasmic KLF4 expression are a potentially unfavourable prognostic factor for patients with NPC. [ABSTRACT FROM AUTHOR]