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ObjectiveTo investigate the diagnostic efficacy of the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model based on ultrasonographic radiomics for the differentiation of small clear cell Renal Cell Carcinoma (ccRCC) and Renal Angiomyolipoma (RAML).MethodsThe clinical, ultrasound, and contrast-enhanced CT(CECT) imaging data of 302 small renal tumors (maximum diameter ≤ 4cm) patients in Tianjin Medical University Cancer Institute and Hospital from June 2018 to June 2022 were retrospectively analyzed, with 182 patients of ccRCC and 120 patients of RAML. The ultrasound images of the largest diameter of renal tumors were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from ROI segmented images. The patients were randomly divided into training and internal validation cohorts in the ratio of 7:3. The Random Forest algorithm of the Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and comprehensive model. The efficacy of the prediction models was verified in an independent external validation cohort consisting of 69 patients, from 230 small renal tumor patients in two different institutions. The Delong test compared the predictive ability of three models and CECT. Calibration Curve and clinical Decision Curve Analysis were applied to evaluate the model and determine the net benefit to patients.Results491 ultrasonographic radiomics features were extracted from 302 small renal tumor patients, and 9 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. In the internal validation cohort, the area under the curve (AUC), sensitivity, specificity, and accuracy of the clinical ultrasound imaging model, ultrasonographic radiomics model, comprehensive model, and CECT were 0.75, 76.7%, 60.0%, 70.0%; 0.80, 85.6%, 61.7%, 76.0%; 0.88, 90.6%, 76.7%, 85.0% and 0.90, 92.6%, 88.9%, 91.1%, respectively. In the external validation cohort, AUC, sensitivity, specificity, and accuracy of the three models and CECT were 0.73, 67.5%, 69.1%, 68.3%; 0.89, 86.7%, 80.0%, 83.5%; 0.90, 85.0%, 85.5%, 85.2% and 0.91, 94.6%, 88.3%, 91.3%, respectively. The DeLong test showed no significant difference between the clinical ultrasound imaging model and the ultrasonographic radiomics model (Z=-1.287, P=0.198). The comprehensive model showed superior diagnostic performance than the ultrasonographic radiomics model (Z=4. 394, P

Background and aimsPatients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure.MethodsThis retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab).ResultsA total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p

IntroductionApplying transumbilical laparoendoscopic single-site surgery to endometrial cancers is worldwide, and the depiction of the learning curve is rarely described, which leads to the vagueness of young clinical practitioners. We accumulated the data to identify the completion of the learning curve by analyzing the operative and postoperative outcomes of the patients with endometrial cancer for transumbilical laparoendoscopic single-site surgery (TU-LESS).MethodsThis was a retrospective, consecutive single-center study of patients with endometrial cancer undergoing standard endometrial cancer comprehensive staging surgery (extrafascial hysterectomy, bilateral salpingectomy, and pelvic lymphadenectomy) through TU-LESS by an experienced surgeon from December, 2017 to June, 2021 in the Department of Gynecologic Oncology, West China Second Hospital, Sichuan University, China.ResultsAfter applying the inclusion and exclusion criteria, 42 patients were included in the study. The learning curve for this study was evaluated using both cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) methods. Applying CUSUM and RA-CUSUM has grouped 42 cases into three phases. The prior five cases represented the learning period. The following six cases were needed to lay a technical foundation (cases 6–11). The third phase was regarded as achieving proficiency (cases 12–42). The operative time decreased drastically with the learning curve. There were no significant differences in terms of postoperative complications and lymph node retrieval among the three phases. More difficult patients were confronted in the third phase.DiscussionIn our study, the learning curve was composed of three phases. According to the results of our study, 11 cases were required for experienced surgeons to achieve a technical foundation.

Hepatosplenic T cell lymphoma (HSTCL) is a particularly difficult-to-treat form of lymphoma, with many patients exhibiting primary resistance to chemotherapy. At present, no effective strategy for treating relapsed and refractory HSTCL has been established, with treatment being hampered by questions of how best to overcome chemoresistance to allow patients to attain more durable therapeutic benefits. While there have been marked advances in immunotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the primary approaches to curing HSTCL. Of patients who undergo immunochemotherapeutic treatment, many are resistant to conventional chemotherapeutic drugs yet remain sensitive to radiotherapy. We selected to employ a transplant pretreatment regimen consisting of total -body irradiation (TBI) and administered this regimen to two patients with HSTCL. Both patients achieved complete remission (CR) after transplantation, demonstrating extended periods without disease recurrence. We systematic reviewed previously published instances involving allo-HSCT in patients with HSTCL. We have found a total of 67 patients who have received allo-HSCT. In general, age

IntroductionOsimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence.MethodsTo reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy.ResultsPanellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made.DiscussionThis study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment.

BackgroundAlthough single-port laparoscopy surgery has been evaluated for several years, it has not been widely adopted by gynecologic oncologists. The objective was to compare the perioperative outcomes and survival of endometrial cancer (EC) patients undergoing transumbilical laparoendoscopic single-site surgery (TU-LESS) with multi-port laparoscopic surgery (MLS).Materials and methodsThis is a retrospective comparative monocentric study including patients treated between December 2017 and October 2021. The perioperative outcomes and survival of EC patients who had surgery via TU-LESS or MLS were compared, by propensity matching.ResultsA total of 156 patients were included (TU-LESS vs. MLS: 78 vs. 78). The conversion rate of TU-LESS and MLS was 5.13% and 2.56%, respectively (P=0.681). The operation time was comparable between the two groups [207.5min (180-251) vs. 197.5min (168.8-225), P=0.095]. There was no significant difference between the two groups in exhaustion time, perioperative complications, or postoperative complications. While, the TU-LESS group had a shorter out-of-bed activity time [36 hours (24-48) vs. 48 hours (48-72), P

BackgroundWhether the albumin-to-globulin ratio (AGR) predicts the prognosis of renal cell carcinoma (RCC) remains controversial. Herein, we performed a meta-analysis to critically evaluate the relationship between the AGR and RCC prognosis, as well as the association between the AGR and the clinicopathological characteristics of RCC.MethodsThe PubMed, Web of Science, Embase, and Cochrane Library databases were thoroughly and comprehensively searched from their inception until 24 June 2023. To determine the predictive significance of the AGR, hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated from the pooled data. The relationship between the AGR and the clinicopathological features of RCC was evaluated by estimating odds ratios (ORs) and 95% CIs in subgroup analyses.ResultsThe meta-analysis included nine articles involving 5,671 RCC cases. A low AGR significantly correlated with worse overall survival (OS) (HR = 1.82, 95% CI = 1.37–2.41, p

Extrachromosomal DNA (ecDNA) is circular DNA that plays an important role in the development and heterogeneity of cancer. The rapid evolution of methods to detect ecDNA, including microscopic and sequencing approaches, has greatly enhanced our knowledge of the role of ecDNA in cancer development and evolution. Here, we review the molecular characteristics, functions, mechanisms of formation, and detection methods of ecDNA, with a focus on the potential clinical implications of ecDNA in cancer. Specifically, we consider the role of ecDNA in acquired drug resistance, as a diagnostic and prognostic biomarker, and as a therapeutic target in the context of cancer. As the pathological and clinical significance of ecDNA continues to be explored, it is anticipated that ecDNA will have broad applications in the diagnosis, prognosis, and treatment of patients with cancer.

BackgroundLong non-coding RNAs (lncRNAs) are increasingly recognized as essential players in various biological processes due to their interactions with DNA, RNA, and protein. Emerging studies have demonstrated lncRNAs as prognostic biomarkers in multiple cancers. However, the prognostic effect of lncRNA AL161431.1 in head and neck squamous cell carcinoma (HNSCC) patients has not been reported.MethodsIn the present study, we conducted a series of analyses to identify and validate the prognostic value of lncRNA AL161431.1 in HNSCC, which included differential lncRNAs screening, survival analysis, Cox regression analysis, time ROCanalysis, nomogram prediction, enrichment analysis, tumor infiltration of immune cells, drug sensitivity analysis, and quantitative real-time polymerase chain reaction (qRT-PCR).ResultsIn this study, we performed a comprehensive survival and predictive analysis and demonstrated that AL161431.1 was an independent prognostic factor of HNSCC, for which a high AL161431.1 level indicated poor survival in HNSCC. Functional enrichment analyses found that cell growth and immune-related pathways were significantly enriched in HNSCC, suggesting that AL161431.1 may play a role in tumor development and tumor microenvironment (TME). AL161431.1-related immune cells infiltration analysis demonstrated that AL161431.1 expression is significantly positively associated with M0 macrophages in HNSCC (P

BackgroundThe prognosis of several malignancies has been influenced by the systemic immune-inflammation index (SII); however, its association with the prognostic outcome of ovarian cancer (OC) remains controversial. The present meta-analysis focused on the systemic and comprehensive identification of the role of SII in predicting OC prognosis.MethodsWe searched the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) from inception until March 6, 2023. To predict the prognostic value of SII for overall survival (OS) and progression-free survival (PFS) in patients with OC, we calculated pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs).ResultsThe meta-analysis included six studies involving 1546 patients. The combined results showed that a high SII was significantly associated with poor OS (HR=2.70, 95% CI=1.98–3.67, p

BackgroundThis study aimed to evaluate the prognosis of the T3 non-small cell lung cancer (NSCLC) patients with additional tumor nodules in the same lobe (T3-Add), and externally validate the current T category of this population.MethodsNSCLC data deposited in the Surveillance, Epidemiology, and End Results (SEER) dataset was extracted. Survivals were estimated using the Kaplan-Meier method with a log-rank test. Propensity score matching (PSM) was performed to reduce bias. The least absolute shrinkage and selection operator (LASSO)-penalized Cox model was used to determine the prognostic factors.ResultsA total of 41,370 eligible cases were included. There were 2,312, 20,632, 12,787, 3,374 and 2,265 cases in the T3-Add, T1, T2, T3 and T4 group, respectively. The Kaplan-Meier curves demonstrated that the survivals of the T3-Add patients were superior to those of the T3 patients both before and after PSM. Additionally, the OS of the T3-Add patients were worse than that of the T2 patients, but the CSS differences between these two groups were not statistically significant. In the subset analyses, the survivals of the T3-Add patients were inferior to those of the T2a patients, but were comparable to those of the T2b patients (5-year OS rate: 54.3% vs. 57.2%, P = 0.884; 5-year CSS rate: 76.2% vs. 76.8%, P = 0.370). In the T3-Add & T2b matched pair, multivariable Cox analysis further confirmed that T category was not a prognostic factor for survivals.ConclusionT3-Add and T2b NSCLC patients had similar survivals, and we proposed that it is necessary to reconsider the T category of the patients with additional nodules in the same lobe in the forthcoming 9th edition of TNM staging manual.

BackgroundSurgery, including lobectomy and segmentectomy, is the major curative intervention for lung cancer. Surgical planning for pulmonary surgery is difficult due to the high variation rate of pulmonary arteries and needs a fine-grained atlas as a reference. We conducted a study to create a surgically oriented atlas and analyzed the error encountered during the production.MethodA total of 100 Chest CTs performed at Peking University People’s Hospital from 2013.09 to 2020.10 were randomly selected for segmental artery labeling. Dicom files were collected for 3D reconstruction. Manual segmentation of each segmental artery was performed by 4 thoracic surgeons. Cross-validation by surgeons was performed to establish the golden standard based on their consensus. Initial recognition errors were recorded accordingly.ResultThe most frequently seen variants for the right upper lobe is 2-branch RA1+2rec+3 and RA2asc; right middle lobe 2-branch RA4a and RA4b+5; right lower lobe 3-branch RA7, RA8 and RA9+10; left upper lobe 3-branch LA1+2a+3, LA1+2b, LA1+2c and 1-branch LA4+5; left lower lobe 2-branch LA8 and LA9+10. Top 5 segmental error occurs in RA4 (23%), LA8 (17%), RA9 (17%), RA8 (14%) and LA9 (11%). A rapid surgical planning tool form was created based on high frequency anatomic variants.ConclusionOur research provided an atlas for lobectomy and segmentectomy at the subsegmental or more distal level. We demonstrated that the recognition accuracy of pulmonary arteries in a non-time-sensitive experimental scenario was still unfavorable. We also suggest that extra attention should be paid to certain surgeries during the surgical planning process.

PurposeHypertrophic pachymeningitis associated with immunoglobulin G4-related disease (IgG4-RD) has been rarely reported, and there is little information and no clear consensus on the management of IgG4-related spinal pachymeningitis (IgG4-RSP). The present study described its possible clinical features, including the symptoms, imaging, treatment and prognosis of patients with IgG4-RSP.MethodsWe report three patients who presented with progressive neurological dysfunction due to spinal cord compression. Relevant articles were searched from the PubMed, Web of Science, and Embase databases, and the resulting literature was reviewed.ResultsThe literature review provided a summary of 45 available cases, which included three cases from our center. Progressive worsening of neurological impairment was observed in 22 patients (48.9%). The lesions involved the thoracic spine (n=28, 62.2%), cervical spine (n=26, 57.8%), lumbar spine (n=9, 20.0%), and sacral spine (n=1, 2.2%). Furthermore, the lesions were located in the dura mater (n=18, 40.0%), epidural space (n=17, 37.8%), intradural-extramedullary space (n=9, 20.0%), and intramedullary space (n=1, 2.2%). On magnetic resonance imaging (MRI), the lesions generally appeared as striated, fusiform, or less often lobulated oval changes, with homogeneous (n=17,44.7%) and dorsal (n=15,39.5%) patterns being the most common. Thirty-five patients had homogeneous T1 gadolinium enhancement. Early surgical decompression, corticosteroid treatment, and steroid-sparing agents offered significant therapeutic advantages. A good therapeutic response to disease recurrence was observed with the medication.ConclusionThe number of reported cases of IgG4-RSP remains limited, and patients often have progressive worsening of their neurological symptoms. The features of masses identified on the MRI should be considered. The prognosis was better with decompression surgery combined with immunosuppressive therapy. Long-term corticosteroid treatment and steroid-sparing agent maintenance therapy should be ensured. A systemic examination is recommended to identify the presence of other pathologies.

The incidence of hepatocellular carcinoma (HCC) associated with extrahepatic primary malignancy (EHPM) is extremely rare, especially for those that involve primary renal cell carcinoma (PRC). Here we present a case of a 66-year-old male who was diagnosed with HCC complicated with lymph node metastasis at posterior pancreas head and PRC. Biopsy results of the liver and the lymph node confirmed the diagnosis of HCC. The disease progressions of both HCC and PRC are controlled effectively following the initiation of comprehensive therapy including pembrolizumab, lenvatinib, radiotherapy, and transcatheter arterial chemo-embolization (TACE). Ultimately, the patient had successfully access to surgery and complete response (CR) of all the tumors were achieved after surgery.

The high detection rate of pulmonary subsolid nodules (SSN) is an increasingly crucial clinical issue due to the increased number of screening tests and the growing popularity of low-dose computed tomography (LDCT). The persistence of SSN strongly suggests the possibility of malignancy. Guidelines have been published over the past few years and guide the optimal management of SSNs, but many remain controversial and confusing for clinicians. Therefore, in-depth research on the natural growth history of persistent pulmonary SSN can help provide evidence-based medical recommendations for nodule management. In this review, we briefly describe the differential diagnosis, growth patterns and rates, genetic characteristics, and factors that influence the growth of persistent SSN. With the advancement of radiomics and artificial intelligence (AI) technology, individualized evaluation of SSN becomes possible. These technologies together with liquid biopsy, will promote the transformation of current diagnosis and follow-up strategies and provide significant progress in the precise management of subsolid nodules in the early stage of lung cancer.

BackgroundThere is a paucity of data published on the clinicopathological features and prognosis of stage IV non-small cell lung cancer (NSCLC) patients aged ≤45 years. Herein, we evaluated a large clinical series in an effort to provide a clearer picture of this population.MethodsThe least absolute shrinkage and selection operator (LASSO)-penalized Cox regression model was performed to identify prognostic factors for NSCLC among individuals aged ≤45 years. The Kaplan–Meier method with log-rank test was used to compare overall survival (OS) differences between groups. Competing risk analysis with the Fine–Gray test was used to analyze cancer-specific survival (CSS) differences. Propensity score matching (PSM) was used to minimize selection bias.ResultsIncidence-rate analyses, including 588,680 NSCLC cases (stage IV, 233,881; age ≤ 45 years stage IV, 5,483; and age > 45 years stage IV, 228,398) from 2004 to 2015, showed that the incidence of stage IV NSCLC among young individuals decreased over the years. In comparative analyses of clinical features and survival outcomes, a total of 48,607 eligible stage IV cases (age ≤ 45 years stage IV, 1,390; age > 45 years stage IV, 47,217) were included. The results showed that although patients in the young cohort were more likely to be diagnosed at advanced stages, they were also more likely to receive aggressive treatments. In addition, the survival rates of the young patients were superior to those of the older patients both before and after PSM.ConclusionsStage IV NSCLC patients aged ≤45 years comprise a relatively small but special NSCLC subgroup. Although this population had better survival outcomes than older patients, these patients deserve more attention due to their young age and the significant socioeconomic implications.

Bacteria are important symbionts for humans, which sustain substantial influences on our health. Interestingly, some bastrains have been identified to have therapeutic applications, notably for antitumor activity. Thereby, oncologists have developed various therapeutic models and investigated the potential antitumor mechanisms for bacteria-mediated cancer therapy (BCT). Even though BCT has a long history and exhibits remarkable therapeutic efficacy in pre-clinical animal models, its clinical translation still lags and requires further breakthroughs. This review aims to focus on the established strains of therapeutic bacteria and their antitumor mechanisms, including the stimulation of host immune responses, direct cytotoxicity, the interference on cellular signal transduction, extracellular matrix remodeling, neoangiogenesis, and metabolism, as well as vehicles for drug delivery and gene therapy. Moreover, a brief discussion is proposed regarding the important future directions for this fantastic research field of BCT at the end of this review.

BackgroundThe recognition of anatomical variants is essential in preoperative planning for lung cancer surgery. Although three-dimensional (3-D) reconstruction provided an intuitive demonstration of the anatomical structure, the recognition process remains fully manual. To render a semiautomated approach for surgery planning, we developed an artificial intelligence (AI)–based chest CT semantic segmentation algorithm that recognizes pulmonary vessels on lobular or segmental levels. Hereby, we present a retrospective validation of the algorithm comparing surgeons’ performance.MethodsThe semantic segmentation algorithm to be validated was trained on non-contrast CT scans from a single center. A retrospective pilot study was performed. An independent validation dataset was constituted by an arbitrary selection from patients who underwent lobectomy or segmentectomy in three institutions during Apr. 2020 to Jun. 2021. The golden standard of anatomical variants of each enrolled case was obtained via expert surgeons’ judgments based on chest CT, 3-D reconstruction, and surgical observation. The performance of the algorithm is compared against the performance of two junior thoracic surgery attendings based on chest CT.ResultsA total of 27 cases were included in this study. The overall case-wise accuracy of the AI model was 82.8% in pulmonary vessels compared to 78.8% and 77.0% for the two surgeons, respectively. Segmental artery accuracy was 79.7%, 73.6%, and 72.7%; lobular vein accuracy was 96.3%, 96.3%, and 92.6% by the AI model and two surgeons, respectively. No statistical significance was found. In subgroup analysis, the anatomic structure-wise analysis of the AI algorithm showed a significant difference in accuracies between different lobes (p = 0.012). Higher AI accuracy in the right-upper lobe (RUL) and left-lower lobe (LLL) arteries was shown. A trend of better performance in non-contrast CT was also detected. Most recognition errors by the algorithm were the misclassification of LA1+2 and LA3. Radiological parameters did not exhibit a significant impact on the performance of both AI and surgeons.ConclusionThe semantic segmentation algorithm achieves the recognition of the segmental pulmonary artery and the lobular pulmonary vein. The performance of the model approximates that of junior thoracic surgery attendings. Our work provides a novel semiautomated surgery planning approach that is potentially beneficial to lung cancer patients.

BackgroundWith increased survival in breast cancer, resulting from advances in treatment, patients incur the possibility of subsequent primary malignancies, especially lung cancer. The aim of this study was to assess the frequency of CT-detected pulmonary ground-glass nodules and lung cancer following breast cancer diagnosis, the associations between breast cancer and lung cancer, the pathological features of double primary cancer, and the status of epidermal growth factor receptor (EGFR) mutations in second primary lung cancer.MethodsClinical data from more than 9000 individuals who were diagnosed with primary breast cancer at Jiangsu Province Hospital (Jiangsu, China) between January 2008 and December 2021 were retrospectively analyzed.ResultsOf the 9179 patients, 6512 underwent diagnostic CT, 55 (0.8%) were diagnosed with a second primary lung cancer, which accounted for approximately 18.4% of the pulmonary ground-glass nodules (GGNs) detected. The incidence was higher than in the general female population (standardized incidence ratio 1.4 [95% confidence interval (CI): 1.25-1.55]). Patients who experienced a second primary lung cancer exhibited a significantly higher rate of EGFR mutation (78.5%) than those with lung adenocarcinoma alone, with most exhibiting low-grade malignancy, older age, estrogen receptor negativity, low Ki67, and no lymph node metastasis.ConclusionsBreast cancer patients, especially those with low-grade malignancy, were at high risk for developing primary lung cancer. For isolated GGN in patients with high-risk factors, clinicians should insist on close follow-up. Furthermore, EGFR may play an important role in primary lung adenocarcinomas and breast cancer.

Giant cell tumor of bone is a highly invasive benign tumor with a high postoperative recurrence rate. Objective: This study aims to analyze the research hotspots and trends of global research on giant cell tumor of bone in the past 20 years, to provide a reference for relevant personnel in this field to carry out academic research. Methods: The literature related to giant cell tumor of bone from 2001 to 2021 was retrieved from the Web of Science. The bibliometrics research method and VOS Viewer were used to extract and analyze the keywords of the journal authors’ research institutions, and the research status and development direction in the recent 20 years were visualized. Results: A total of 2063 articles were included. The number of global publications is increasing every year. The United States contributes the most to global research, with the most citations and the highest H-index. The journal Clinical Orthopaedics and Related Research published the most articles on this issue. “Denosumab” and “h3f3a” will get more attention and be the next popular hotspot in the future. Conclusion: The study of giant cell tumor of bone is a hot spot of continuous development and has an important contribution to human health.

The BTN2/3 subfamilies are overexpressed in many cancers, including pan-glioma (low- and high-grade gliomas). However, the expression and prognosis of BTN2/3 subfamilies and tumor-infiltrating lymphocytes in pan-glioma remain unknown. In the present study, we systematically explored and validated the expression and prognostic value of BTN2/3 subfamily members in pan-glioma [The Cancer Genome Atlas–glioblastoma and low-grade glioma (TCGA-GBMLGG) merge cohort] using multiple public databases. We used clinical specimens for high-throughput verification and cell lines for qRT-PCR verification, which confirmed the expression profiles of BTN2/3 subfamilies. In addition, the function of the BTN2/3 subfamily members and the correlations between BTN2/3 subfamily expression and pan-glioma immune infiltration levels were investigated. We found that BTN2/3 subfamily members were rarely mutated. BTN2/3 subfamilies were overexpressed in pan-glioma; high expression of BTN2/3 subfamily members was correlated with poor prognosis. In addition, BTN2/3 subfamilies might positively regulate proliferation, and the overexpression of BTN2/3 subfamilies influenced cell cycle, differentiation, and glioma stemness. In terms of immune infiltrating levels, BTN2/3 subfamily expression was positively associated with CD4+ T-cell, B-cell, neutrophil, macrophage, and dendritic cell infiltrating levels. These findings suggest that BTN2/3 subfamily expression is correlated with prognosis and immune infiltration levels in glioma. Therefore, the BTN2/3 subfamilies can be used as biomarkers for pan-glioma and prognostic biomarkers for determining the prognosis and immune infiltration levels in pan-glioma.

AimTo determine the ideal surgical approach for Siewert type II EGJ carcinomas.MethodsWe conducted the randomized controlled trial (RCT) at Shanxi Cancer Hospital from January 2014 to August 2016. A total of 105 patients with T1-4N1-3M0 Siewert type II EGJ carcinomas were initially recruited. The final follow-up was up to June 30, 2019. Patients were randomized to undergo either a proximal gastrectomy plus jejunal interposition (PG+JI), proximal gastrectomy plus esophagogastrostomy (PG+EG), or total gastrectomy plus Roux-en-Y esophagojejunostomy (TG+RY). The primary endpoint was postoperative complications. Secondary endpoints were 5-year survival and recovery indexes.ResultsAmong 105 patients, 100 patients (95.2%; mean age, 56.2 years) with tumors

Autotaxin (ATX) is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA), a growth factor-like signaling phospholipid. ATX has been abundantly detected in the culture medium of various cancer cells, tumor tissues, and serum or plasma of cancer patients. Biological actions of ATX are mediated by LPA. The ATX-LPA axis mediates a plethora of activities, such as cell proliferation, survival, migration, angiogenesis, and inflammation, and participates in the regulation of various physiological and pathological processes. In this review, we have summarized the physiological function of ATX and the ATX-LPA axis in liver cancer, analyzed the role of the ATX-LPA axis in tumorigenesis and metastasis, and discussed the therapeutic strategies targeting the ATX-LPA axis, paving the way for new therapeutic developments.

BackgroudTumor grade is the determinant of the biological aggressiveness of pancreatic neuroendocrine tumors (PNETs) and the best current tool to help establish individualized therapeutic strategies. A noninvasive way to accurately predict the histology grade of PNETs preoperatively is urgently needed and extremely limited.MethodsThe models training and the construction of the radiomic signature were carried out separately in three-phase (plain, arterial, and venous) CT. Mann–Whitney U test and least absolute shrinkage and selection operator (LASSO) were applied for feature preselection and radiomic signature construction. SVM-linear models were trained by incorporating the radiomic signature with clinical characteristics. An optimal model was then chosen to build a nomogram.ResultsA total of 139 PNETs (including 83 in the training set and 56 in the independent validation set) were included in the present study. We build a model based on an eight-feature radiomic signature (group 1) to stratify PNET patients into grades 1 and 2/3 groups with an AUC of 0.911 (95% confidence intervals (CI), 0.908–0.914) and 0.837 (95% CI, 0.827–0.847) in the training and validation cohorts, respectively. The nomogram combining the radiomic signature of plain-phase CT with T stage and dilated main pancreatic duct (MPD)/bile duct (BD) (group 2) showed the best performance (training set: AUC = 0.919, 95% CI = 0.916–0.922; validation set: AUC = 0.875, 95% CI = 0.867–0.883).ConclusionsOur developed nomogram that integrates radiomic signature with clinical characteristics could be useful in predicting grades 1 and 2/3 PNETs preoperatively with powerful capability.

PurposeTreatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS).Patients and MethodsMedical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell’s concordance index (C-index) and calibration curve.ResultsThe C-index values were 0.82 (95% CI: 0.76–0.88) and 0.84 (95% CI: 0.78–0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/.ConclusionA externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.

We aimed to elucidate the mechanism by which hepatitis B virus X (HBx) mutations increase the occurrence of hepatocellular carcinoma (HCC) and identify novel putative therapeutic targets. Wild-type HBx (WT-HBx) and four HBx mutants (M1, A1762T/G1764A; M2, T1674G+T1753C+A1762T/G1764A; M3, C1653T+T1674G+A1762T/G1764A; and Ct-HBx, carboxylic acid-terminal truncated HBx) were delivered into Sleeping Beauty (SB) mouse models. The HCC incidence was higher in the M3-HBx- and Ct-HBx-injected SB mice. M3-HBx had a stronger capacity of upregulating inflammatory cytokines than other HBx variants. Ectopic expression of M3-HBx and Ct-HBx significantly increased proliferation and S phase proportion of HepG2 and HeLa cells, compared to WT-HBx. Plasminogen activator inhibitor-1 (PAI1) and cell division cycle 20 (CDC20) were identified as novel effectors by cDNA microarray analysis. M3-HBx and Ct-HBx significantly upregulated the expression of PAI1 and CDC20 in HepG2 and HeLa cells as well as the livers of SB mice. Silencing PAI1 attenuated the effects of M3-HBx and Ct-HBx on the growth of HepG2 and HeLa cells. PAI1, an important player bridging the HBx mutants and HCC, should be a promising candidate as a prognostic biomarker and therapeutic target in HBV-related HCC.

ObjectiveMetastatic spinal dissemination (MSD) of supratentorial glioma is very rare and there is no established standard of care. The current study investigates the clinical characteristics and course of spinal dissemination of supratentorial glioma.MethodsA retrospective analysis of adult patients with MSD of supratentorial glioma treated in the Department of Oncology in Beijing Shijitan Hospital, Capital Medical University from June 2012 until August 2021 was performed. The time to event was estimated using Kaplan–Meier analysis. Univariate analyses were performed using log-rank test and multivariate analysis was performed using the Cox proportional hazards model.ResultsThirty-four adult patients with MSD of supratentorial glioma were enrolled in this retrospective study. The median time to MSD (TTMSD) and overall survival (OS) were 5 months (range: 0–78 months) and 15 months (range: 0.7–85 months), respectively, in the entire cohort. Univariate analysis demonstrated that the patients who had received TMZ therapy had a longer TTMSD than those who did not (mTTMSD: 15 vs. 3 months, log-rank P = 0.0004). Furthermore, a protracted duration of salvage chemotherapy of >6 months after MSD was associated with longer OS of the patients with MSD of supratentorial glioma (mOS: 13 vs. 5 months, log-rank P = 0.0163) and reduced the death risk by 64.3% (hazard ratio: 0.357, 95% CI: 0.141–0.901, P = 0.029) compared with a duration ≤6 months.ConclusionPatients with MSD of supratentorial glioma experienced poor prognosis and adjuvant chemotherapy may delay the occurrence of MSD. The protracted duration of systemic salvage chemotherapy may favor survival after spinal dissemination.

BackgroundPrimary central nervous system lymphoma (PCNSL) is characterized by a lack of specificity and poor prognosis. Further understanding of the tumor heterogeneity and molecular phenotype of PCNSL is of great significance for improving the diagnosis and treatment of this disease.MethodsTo explore the distinct phenotypic states of PCNSL, transcriptome-wide single-cell RNA sequencing was performed on 34,851 PCNSL cells from patients. The cell types, heterogeneity, and gene subset enrichment of PCNSL were identified. A comparison of the PCNSL cells with 21,250 normal human fetal brain (nHFB) cells was further analyzed to reveal the differences between PCNSL and normal sample.ResultsSix cell populations were mainly identified in the PCNSL tissue, including four types of immune cells—B cell, T cell, macrophage and dendritic cell—and two types of stromal cells: oligodendrocyte and meningeal cell. There are significant cellular interactions between B cells and several other cells. Three subpopulations of B cells indicating diffident functions were identified, as well as a small number of plasma cells. Different subtypes of T cells and dendritic cells also showed significant heterogeneity. It should be noted that, compared with normal, the gene expression and immune function of macrophages in PCNSL were significantly downregulated, which may be another important feature of PCNSL in addition to B cell lesions and may be a potential target for PCNSL therapy.

BackgroundCervical small cell neuroendocrine carcinoma (SCNC) is a rare and aggressive disease that lacks a standard treatment strategy or effective methods of targeted therapy. PD-L1 inhibitors for DNA mismatch repair system-deficient (dMMR) tumors and neurotrophin receptor tyrosine kinase (NTRK) inhibitors offer potential pan-cancer treatments.MethodsImmunohistochemistry was employed as the main detection method, and any NTRK positive cases, identified by immunohistochemistry, were further submitted for evaluation by fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (RT-PCR) methods.ResultsForty-six patients were enrolled. Positive PD-L1 expression was seen in 22 of the 43 patients (51.16%) with an average combined positive score of 6.82. PD-L1-positive patients were more likely to have a higher proliferation rate in the tumor, and they experienced less recurrence and death (p = 0.048 and 0.033, respectively) compared with the patients with negative PD-L1 expression. However, in the multivariate analysis, none of the clinical parameters was associated with the expression of PD-L1. There was no association between PD-L1 expression and disease recurrence or overall survival in the Kaplan-Meier analysis. All cases were found to be MMR-stable and lacked NTRK gene fusion. However, pan-Trk expressed in 14 (32.56%) of the 43 tested cases, but FISH and RT-PCR failed to confirm any positive fusion signals in IHC-positive cases.ConclusionsPD-L1 may be an effective therapeutic target for cervical SCNC. Cervical SCNC is a MMR-stable tumor and lacks NTRK gene fusion. IHC isn’t a reliable method in the detection of NTRK gene fusion in cervical SCNC.

Background and AimsNodular ground-glass lesions have become increasingly common with the increased use of computed tomography (CT), while the genomic features of ground-glass opacities (GGOs) remain unclear. This study aims to comprehensively investigate the molecular alterations of GGOs and their correlation with radiological progression.MethodsStudies from PubMed, Embase, Cochrane Library, and Web of Science, using PCR, targeted panel sequencing, whole exosome sequencing, and immunohistochemistry, and reporting genomic alterations or PD-L1 expressions in lung nodules presenting as GGOs until January 21, 2021 were included in this study. Chi-square test, random-effects model, and Z-test analysis were adopted to analyze the data.ResultsA total of 22 studies describing mutations in lung adenocarcinoma (LUAD) with GGOs were analyzed. EGFR was the most frequently mutative gene (51%, 95%CI 47%–56%), followed by TP53 (18%, 95%CI 6%–31%), HER2 (10%, 95%CI 0%–21%), ROS1 (6%, 95%CI 0%–18%), and KRAS (6%, 95%CI 3%–9%). The correlation between the frequency of EGFR mutation and radiological was observed and the differences were found to be not statistically significant in the subgroups, which are listed as below: radiological: gGGO 47.40%, 95%CI [38.48%; 56.40%]; sGGO 51.94%, 95%CI [45.15%; 58.69%]. The differences of the frequency of KRAS mutation in the different subgroups were also consistent with this conclusion, which are listed as: radiological gGGO 3.42, 95%CI [1.35%; 6.13%]; sGGO 12.27%, 95%CI [3.89%; 23.96%]. The pooled estimated rate of PD-L1 was 8.82%, 95%CI [5.20%–13.23%]. A total of 11.54% (3/26) of the SMGGNs were confirmed to be intrapulmonary spread by WES.ConclusionsSomatic genetic alterations are considered in early-stage GGO patients without distinct changes of the frequency following the progress of the tumor. This review sheds insight on molecular alterations in LUAD with GGOs.

ObjectiveThis study aims to compare the clinical and pathological characteristics between patients undergoing surgery for extremely multiple ground-glass nodules (GGNs) and those for single GGN.MethodsWe defined extremely multiple GGNs as follows: (i) number of GGNs ≥3, (ii) GGN diameter between 3 and 30 mm, and (iii) no less than three nodules that were surgically removed and pathologically diagnosed. Patients with extremely multiple GGNs and single GGNs who underwent surgery at the same time were retrospectively analyzed. The patients were divided into three groups according to the number of nodules: exceedingly multiple nodules (EMN) group (>10), highly multiple nodules (HMN) group (three to 10), and single nodule (SN) group. The clinical and pathological characteristics, surgical methods and prognosis were analyzed.ResultsNinety-nine patients with single nodules and 102 patients with extremely multiple nodules were enrolled. Among the patients with extremely multiple nodules, 43 (42.2%) had >10 nodules. There were no significant differences in demographic characteristics, such as age, sex, and smoking history, between the groups, but there were differences in tumor characteristics. All patients with >10 nodules showed bilateral pulmonary nodules and presented with both pure and mixed GGNs. The single GGNs were smaller in diameter, and the proportion of mixed GGNs and pathologically invasive adenocarcinoma was lower than that of the primary nodules in the exceedingly multiple GGNs group (p < 0.05). However, the proportion of both mixed GGNs and malignant nodules decreased significantly with the increasing number of total lesions. During postoperative follow-up, one patient in the highly multiple nodules group had a local recurrence, and 16 (15.7%) patients in the extremely multiple GGNs group and 10 (9.8%) patients in the single GGN group had enlarged unresected GGNs or additional GGNs.ConclusionsOur study revealed the clinical and pathologic characteristics, surgical methods, and prognosis of patients with extremely multiple GGNs and compared them with those of patients with a single GGN. Although the primary nodules in extremely multiple GGNs may have higher malignancy than those in the single nodule group, the proportion of both mGGNs and malignant nodules decreased significantly with the increasing number of lesions, and the prognosis of patients with extremely multiple GGNs was satisfied.

BackgroundThe role of fetal-lethal non-coding developmental regulatory RNA (FENDRR) has been explored in various cancers; however, its relationship with colon adenocarcinoma/rectum adenocarcinoma (COAD/READ) remains unclear. The objectives of this study were to identify and assess any associations between FENDRR and COAD/READ using The Cancer Genome Atlas (TCGA) database and the Genetic Data Commons (GDC) Data Portal.MethodsThe records of patients with COAD/READ were collected from the GDC Data Portal. After comparing the expression level of FENDRR in COAD/READ and healthy tissues, we evaluated the association of FENDRR with clinicopathological characters and the survival rate, the impact of FENDRR on prognosis, the biological function of FENDRR, and the relative abundance of tumor-infiltrating immune cells in patients with COAD/READ. Moreover, we aimed to construct a protein-protein interaction (PPI) network for selecting genes and a ceRNA network for presenting mRNA-miRNA-lncRNA interactions.ResultsIn patients with COAD/READ, FENDRR expression could differentiate tumor tissues from the adjacent healthy tissues since it was significantly lower in the former than in the latter. High FENDRR expression was correlated with poorer survival and higher tumor stage, current tumor stage, and metastasis stage, and also exhibited high scores for apoptosis, autophagy, and senescence. Immune cell infiltration analysis showed that the high expression group had significantly lower immune and stromal scores. Low FENDRR expression was correlated with poor overall survival (OS), and thus, it could serve as an independent risk factor. The prognostic models constructed in the study performed well for the prediction of OS and disease-specific survival (DFS) using FENDRR expression. Gene set enrichment analysis revealed that vascular smooth muscle contraction, melanogenesis, basal cell carcinoma, and Hedgehog signaling pathways were significantly enriched in patients with high FENDRR expression. Eight hub genes, namely, PKM, ALDOA, PFKP, ALDOC, PYGL, CTNNB1, PSMA5, and WNT5A, were selected from the PPI network, and a ceRNA network was constructed based on the differentially expressed mRNAs, miRNAs, and lncRNAs to illustrate their regulatory relationships.ConclusionFENDRR may serve as a potential biomarker for the diagnosis and prognosis of COAD/READ.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has poor prognosis. Cytokeratin (CK)19-positive (CK19+) HCC is especially aggressive; early identification of this subtype and timely intervention can potentially improve clinical outcomes. In the present study, we developed a preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI)-based radiomics model for noninvasive and accurate classification of CK19+ HCC. A multicenter and time-independent cohort of 257 patients were retrospectively enrolled (training cohort, n = 143; validation cohort A, n = 75; validation cohort B, n = 39). A total of 968 radiomics features were extracted from preoperative multisequence MR images. The maximum relevance minimum redundancy algorithm was applied for feature selection. Multiple logistic regression, support vector machine, random forest, and artificial neural network (ANN) algorithms were used to construct the radiomics model, and the area under the receiver operating characteristic (AUROC) curve was used to evaluate the diagnostic performance of corresponding classifiers. The incidence of CK19+ HCC was significantly higher in male patients. The ANN-derived combined classifier comprising 12 optimal radiomics features showed the best diagnostic performance, with AUROCs of 0.857, 0.726, and 0.790 in the training cohort and validation cohorts A and B, respectively. The combined model based on multisequence MRI radiomics features can be used for preoperative noninvasive and accurate classification of CK19+ HCC, so that personalized management strategies can be developed.

Castration-resistant prostate cancer (CRPC) is the lethal form of prostate cancer (PCa), and the underlying molecular mechanism has not been fully elucidated. Inositol requiring enzyme 1 alpha (IRE1α), a key regulator of unfolded protein response (UPR), is intimately associated with PCa progression. However, whether IRE1α is implicated in CRPC development remains unknown. Here, we showed that IRE1α expression was significantly increased in CRPC tissues and high-grade PCa tissues. Overexpression of IRE1α promoted PCa cell proliferation under the androgen deficiency condition in vitro and in vivo. Mechanistically, increased IRE1α expression induced IL-6 secretion via the IRE1α/XBP-1s signal pathway. IRE1α-induced IL-6 activated androgen receptor (AR), and the activation of AR by IL-6, in turn, promoted IRE1α expression. IRE1α formed a positive feedback loop with IL-6 and AR to promote prostate cancer cell proliferation under the androgen-deficient condition. In clinical PCa samples, high IRE1α expression correlated with elevated IL-6 and increased PSA expression. Our findings demonstrated a novel mechanism of CRPC progression and suggest targeting IRE1α may be a potential target for the prevention and treatment of CRPC.

BackgroundNon-small-cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination are defined as M1a in the eighth of American Joint Committee on Cancer (AJCC) TNM staging. We aimed to build a nomogram to predict lung cancer specific survival (LCSS) of NSCLC patients with ipsilateral pleural dissemination and to compare the impact of primary tumor resection (PTR) on LCSS among patients with different features.MethodsA total of 3,918 NSCLC patients with ipsilateral pleural dissemination were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We selected and integrated significant prognostic factors based on competing risk regression to build a nomogram. The model was subjected to internal validation within SEER cohort and external validation with the cohort of 97 patients from Peking University People’s Hospital.ResultsAge (P < 0.001), gender (P = 0.037), T stage (P = 0.002), N stage (P < 0.001), metastasis pattern (P = 0.005), chemotherapy (P < 0.001), and PTR (P < 0.001) were independent prognostic factors. The calibration curves presented a good consistency and the Harrell’s C-index of nomogram were 0.682 (95%CI: 0.673–0.691), 0.687 (95%CI: 0.670–0.704) and 0.667 (95%CI: 0.584–0.750) in training, internal, and external validation cohort, respectively. Interaction tests suggested a greater LCSS difference caused by PTR in patients without chemotherapy (P < 0.001).ConclusionsWe developed a nomogram based on competing risk regression to reliably predict prognosis of NSCLC patients with ipsilateral pleural dissemination and validated this nomogram in an external Chinese cohort. This novel nomogram might be a practical tool for clinicians to anticipate the 1-, 3- and 5-year LCSS for NSCLC patients with pleural dissemination. Subgroup analysis indicated that patients without chemotherapy could get more benefit from PTR. In order to assess the role of PTR in the management of M1a patients more accurately, further prospective study would be urgently required.

Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC.

PurposeGlioblastoma (GBM) is the most aggressive and lethal type of brain tumors. Magnetic resonance imaging (MRI) has been commonly used for GBM diagnosis. Contrast enhancement (CE) on T1-weighted sequences are presented in nearly all GBM as a result of high vascular permeability in glioblastomas. Although several radiomics studies indicated that CE is associated with distinct molecular signatures in tumors, the effects of vascular endothelial cells, the key component of blood brain barrier (BBB) controlling vascular permeability, on CE have not been thoroughly analyzed.MethodsEndothelial cell enriched genes have been identified using transcriptome data from 128 patients by a systematic method based on correlation analysis. Distinct endothelial cell enriched genes associated with CE were identified by analyzing difference of correlation score between CE-high and CE–low GBM cases. Immunohistochemical staining was performed on in-house patient cohort to validate the selected genes associated with CE. Moreover, a survival analysis was conducted to uncover the relation between CE and patient survival.ResultsWe illustrated that CE is associated with distinct vascular molecular imprints characterized by up-regulation of pro-inflammatory genes and deregulation of BBB related genes. Among them, PLVAP is up-regulated, whereas TJP1 and ABCG2 are down-regulated in the vasculature of GBM with high CE. In addition, we found that the high CE is associated with poor prognosis and GBM mesenchymal subtype.ConclusionWe provide an additional insight to reveal the molecular trait for CE in MRI images with special focus on vascular endothelial cells, linking CE with BBB disruption in the molecular level. This study provides a potential new direction that may be applied for the treatment optimization based on MRI features.

Pancreatic squamous cell carcinoma (SCC) is a rare primary pancreatic malignancy with a poor prognosis. The median overall survival (OS) for metastatic setting is only 4 months and the optimal management remains poorly defined. In the present study, we report a 52-year-old female patient with stage IV primary SCC of the pancreas harboring a deleteous BRCA2 somatic mutation. After 10 cycles of chemotherapy of cisplatin combined with nanoparticle albumin-bound paclitaxel, metastatic lesions in the liver and lymph nodes achieved radiographic complete responses and pancreatic lesion shrank from 5.7 to 1.5 cm in diameter. The patient subsequently underwent a posterior radical antegrade modular pancreatosplenectomy with R0 resection and residual liver lesions were also resected. After 3 months, a tumor relapsed in the liver. She was then treated with olaparib combined with pembrolizumab and achieved stable disease on the liver lesion. The patient eventually died from cerebral hemorrhage with a long OS of 21 months. Our case demonstrated a favorable clinical activity and survival advantage of the combined cisplatin and nanoparticle albumin-bound paclitaxel, which might serve as a therapeutic option for the patient with BRCA-mutant pancreatic SCC.

Introduction: Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence. Methods: To reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy. Results: Panellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made. Discussion: This study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment. [ABSTRACT FROM AUTHOR]

ObjectiveLinc00665 is a novel long non-coding RNA that can promote the progression of breast cancer, but its value in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer has not been reported. We aim to analyze the correlation between Linc00665 expression and pathological complete response (pCR) in breast cancer patients.Materials and MethodsThe present study examined the predictive role of Linc00665 expression in pCR after NAC using both univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the performance of Linc00665 in predicting pCR. The Kyoto Encyclopedia of Gene and Genome (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were also conducted to determine the biological processes where Linc00665 may participate in.ResultsThe present study study totally enrolled 102 breast cancer patients. The univariate analysis showed that Linc00665 level, human epidermal growth factor receptor 2 (HER2) status and hormone receptor (HR) status were correlated with pCR. The multivariate analysis showed that Linc00665 expression was an independent predictor of pCR (OR = 0.351, 95% CI: 0.125–0.936, P = 0.040), especially in patients with HR-positive/HER2-negative subtype (OR = 0.272, 95% CI: 0.104–0.664, P = 0.005). The KEGG analysis indicated that Linc00665 may be involved in drug metabolism. The GSEA analysis revealed that Linc00665 is correlated to DNA damage repair.ConclusionLinc00665 may be a potential novel predictive biomarker for breast cancer in NAC, especially for HR-positive/HER2-negative patients.

Collagen type VI alpha 6 chain (COL6A6), a novel collagen, has been considered as a tumor suppressor and therapeutic target in several tumors. However, the functional role of COL6A6 in immune cell infiltration and prognostic value in lung adenocarcinoma (LUAD) remains unknown. Here, we evaluated COL6A6 expression and its impact on survival among LUAD patients from The Cancer Genome Atlas (TCGA) and several other databases. COL6A6 was downregulated in LUAD tissues compared to normal tissues at both mRNA and protein levels. COL6A6 expression was negatively associated with pathological stage, tumor stage, and lymph node metastasis. High COL6A6 expression was a favorable prognostic factor in LUAD. Next, we explored the associations between COL6A6 expression and immune cell infiltration. COL6A6 expression was positively associated with the infiltration of B cells, T cells, neutrophils and dendritic cells. Additionally, the immune cell infiltration levels were associated with COL6A6 gene copy number in LUAD. Consistently, gene set enrichment analysis showed that various immune pathways were enriched in the LUAD samples with high COL6A6 expression, including pathways related to T cell activation and T cell receptor signaling. The impacts of COL6A6 on immune activity were further assessed by enrichment analysis of 50 COL6A6-associated immunomodulators. Thereafter, using Cox regression, we identified a seven-gene risk prediction signature based on the COL6A6-associated immunomodulators. The resulting risk score was an independent prognostic predictor in LUAD. Receiver operating characteristic curve analysis confirmed that the seven-gene signature had good prognostic accuracy in the TCGA-LUAD cohort and a Gene Expression Omnibus dataset. Finally, we constructed a clinical nomogram to predict long-term survival probabilities, and calibration curves verified its accuracy. Our findings highlight that COL6A6 is involved in tumor immunity, suggesting COL6A6 may be a potential immunotherapeutic target in LUAD. The proposed seven-gene signature is a promising prognostic biomarker in LUAD.

Breast cancer remains a leading cause of cancer-related death, for which the majority of deaths result from metastases. Von Willebrand factor C and EGF domain (VWCE) is a member of the Von Willebrand factor (VWF) gene family; however, its function, regulatory mechanism, and clinical value in breast cancer remain unclear. In the present study, we sought to elucidate the role of VWCE in breast cancer metastasis. We examined the expression of VWCE in breast cancer tissues and normal control tissues of 50 breast cancer patients. We found that VWCE expression was downregulated in breast cancer cells and tissues compared to normal breast epithelial cells or the adjacent normal tissues. To explore the role of VWCE in human breast cancer development, we introduced a VWCE-overexpressing or control lentiviral vector into the breast cancer MDA-MB-453 and MDA-MB-231 lines in vitro. The overexpression of VWCE inhibited the proliferation, migration, invasion, and chemoresistance of the breast cancer cell lines. More importantly, the forced expression of VWCE suppressed tumor formation and metastasis in nude mice. iTRAQ-based quantitative proteomic analysis revealed that VWCE overexpression induced a 10-fold decrease in the level of WD-repeat domain 1 (WDR1) protein expression. Rescue experiments further verified that WDR1 was a downstream molecule of VWCE, and WDR1 overexpression reversed the above effects of VWCE overexpression on tumor growth. Therefore, VWCE may represent a novel tumor suppressor, for which its deregulation promotes breast cancer progression via the upregulation of WDR1.

Background: Apatinib is a powerful inhibitor of vascular endothelial growth factor receptor-2. This study was aimed to investigate whether apatinib could improve the efficacy of transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC).Methods: Between June 2015 and September 2018, 357 patients with HCC at Barcelona Clinic Liver Cancer stage C who received the treatment of TACE combining with apatinib (TACE–apatinib) or TACE-alone were included. Propensity score matching (PSM) analysis was used to reduce the patient selection bias.Results: Ninety pairs of patients were chosen after the PSM analysis. The disease control rates of tumor and a-fetoprotein response in the TACE–apatinib group were significantly higher than that of the TACE-alone group before and after the PSM analysis (P < 0.05). Before the PSM analysis, the median time of tumor progression (TTP) and the overall survival (OS) in the TACE–apatinib group were significantly greater than those of the TACE-alone group (TTP: 9.0 months vs. 3.0 months, P < 0.001; OS: 14.0 months vs. 7.0 months, P < 0.001). After the PSM analysis, the median TTP and OS in the TACE–apatinib group was also significantly greater than that of the TACE-alone group (TTP: 7.0 months vs. 3.0 months, P < 0.001; OS: 13.0 months vs. 8.0 months, P < 0.001); the uni- and multivariate analysis revealed that TACE–apatinib was a protective factor for OS. Fourteen patients emerged with grade 3 apatinib-related adverse events.Conclusion: The efficacy of TACE–apatinib for patients with advanced HCC was inspiring, and the side effects of apatinib were tolerable.

Background: Sirtuin 7 (SIRT7), a protein-coding gene whose abnormal expression and function are associated with carcinogenesis. However, the prognosis of SIRT7 in different breast cancer subtypes and its correlation with tumor-infiltrating lymphocytes remain unclear.Methods: The expression and survival data of SIRT7 in patients with breast cancer were analyzed using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interaction Analysis (GEPIA), The Human Protein Atlas (HPA), UALCAN, Breast Cancer Gene-Expression Miner (BC-GenExMiner), and Kaplan-Meier plotter databases. Also, the expression correlations between SIRT7 and immune infiltration gene markers were analyzed using TIMER and further verified the results using immunohistochemistry.Results: SIRT7 exhibited higher expression levels in breast cancer tissues than the adjacent normal tissues. SIRT7 expression was significantly correlated with sample type, subclass, cancer stage, menopause status, age, nodal status, estrogen receptor (ER), progesterone receptor (PR), and triple-negative status. High SIRT7 expression was associated with poor prognosis in breast cancer-luminal A [overall survival (OS): hazard ratio (HR) = 1.54, p = 1.70e-02; distant metastasis-free survival (DMFS): HR = 1.56, p = 2.60e-03]. Moreover, the expression of SIRT7 was positively correlated with the expression of IRF5 (M1 macrophages marker, r = 0.165, p = 1.13e-04) and PD1 (T cell exhaustion marker, r = 0.134, p = 1.74e-03). These results suggested that the expression of SIRT7 was related to M1 macrophages and T cell exhaustion infiltration in breast cancer-luminal.Conclusions: These findings demonstrate that the high expression of SIRT7 indicates poor prognosis in breast cancer as well as increased immune infiltration levels of M1 macrophages and T cell exhaustion in breast cancer-luminal. Thus, SIRT7 may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in breast cancer-luminal.

Background: We aimed to explore whether the expression of serum miR-222-3p might contribute to early prediction of therapeutic response, clinical outcomes, and adverse events for HER2-positive breast cancer patients receiving neoadjuvant therapy (NAT).Methods: A total of 65 HER2-positive breast cancer patients receiving NAT were analyzed. The concentration of serum miR-222-3p was detected by quantitative real-time PCR. Logistic regression analysis was used to identify the association of serum miR-222-3p with pathological complete response (pCR). The relationship of serum miR-222-3p with disease-free survival (DFS) and overall survival (OS) was examined via log-rank test and Cox proportional hazards analysis. The ordered logistic regression was applied to evaluate the association between serum miR-222-3p and adverse events.Results: The miR-222-3p low group was more likely to achieve pCR [odds ratio (OR) = 0.258, P = 0.043]. The interaction between miR-222-3p and presenting Ki67 level was also detected for pCR (OR = 49.230, Pinteraction = 0.025). The miR-222-3p low group was correlated with superior DFS (P = 0.029) and OS (P = 0.0037). The expression of serum miR-222-3p was the independent protective factor for trastuzumab-induced cardiotoxicity (P < 0.05) and anemia (P = 0.013).Conclusions: Serum miR-222-3p is the potential factor to predict pCR, survival benefit and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving NAT.

Background: Serous cystadenoma (SCA), mucinous cystadenoma (MCN), and intraductal papillary mucinous neoplasm (IPMN) are three subtypes of pancreatic cystic neoplasm (PCN). Due to the potential of malignant-transforming, patients with MCN and IPMN require radical surgery while patients with SCA need periodic surveillance. However, accurate pre-surgery diagnosis between SCA, MCN, and IPMN remains challenging in the clinic.Methods: This study enrolled 164 patients including 76 with SCA, 40 with MCN and 48 with IPMN. Patients were randomly split into a training cohort (n = 115) and validation cohort (n = 41). We performed statistical analysis and Boruta method to screen significantly distinct clinical factors and radiomics features extracted on pre-surgery contrast-enhanced computed tomography (CECT) images among three subtypes. Three reliable machine-learning algorithms, support vector machine (SVM), random forest (RF) and artificial neural network (ANN), were utilized to construct classifiers based on important radiomics features and clinical parameters. Precision, recall, and F1-score were calculated to assess the performance of the constructed classifiers.Results: Nine of 547 radiomics features and eight clinical factors showed a significant difference among SCA, MCN, and IPMN. Five radiomics features (Histogram_Entropy, Histogram_Skeweness, LLL_GLSZM_GLV, Histogram_Uniformity, HHL_Histogram_Kurtosis), and four clinical factors, including serum carbohydrate antigen 19-9, sex, age, and serum carcinoembryonic antigen, were identified important by Boruta method. The SVM classifier achieved an overall accuracy of 73.04% in training cohort and 71.43% in validation cohort, respectively. The RF classifier achieved overall accuracy of 84.35 and 79.59%, respectively. The constructed ANN model showed an overall accuracy of 77.39% in the training dataset and 71.43% in the validation dataset. All the three classifiers showed high F1 score for differentiation among the three subtypes.Conclusion: Our study proved the feasibility and translational value of CECT-based radiomics classifiers for differentiation among SCA, MCN, and IPMN.

Objective: Neutrophil lymphocyte ratio (NLR), Lymphocyte mononuclear cell ratio (LMR), and Platelet lymphocyte ratio (PLR) can be used as various prognostic factors for malignant tumors, but the value of prognosis for patients with adenocarcinoma of the esophagogastric junction (AEG) has not been determined. This study used meta-analysis to assess the value of these indicators in the evaluation of AEG prognosis.Methods: Relevant literatures on the prognostic relationship between NLR, LMR, PLR, and AEG was retrieved from PubMed, Web of Science, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials, Wanfang data, and Chinese National Knowledge Infrastructure. The search time from database establishment to June 30, 2019. The language is limited to English and Chinese. Data was analyzed using Stata 15.0 software.Result: Six retrospective studies were included, five of them involved NLR and six of them involved PLR. No LMR literature that adequately satisfied the conditions was retrieved. Increased NLR was significantly associated with a significant reduction in overall survival (OS), cancer-specific survival (CSS), or disease specific survival (DSS) in patients with AEG [hazard ratio (HR) = 1.545, 95% CI: 1.096–2.179, P < 0.05]. Subgroup analysis showed that NLR had significant value in the prognosis of both Chinese and Non-Chinese patients (P = 0.009 vs. P = 0.000). NLR had significant prognostic value for ≥3 and 0.05). PLR had no significant prognostic value for both Chinese and UK patients (P = 0.282 vs. P = 0.429). PLR had no significant prognostic value for ≥150 group and

Objectives: Tumor pathology examination especially epidermal growth factor receptor (EGFR) mutations molecular testing has been integral part of lung cancer clinical practices. However, the EGFR mutations spatial distribution characteristics remains poorly investigated, which is critical to tumor heterogeneity analysis and precision diagnosis. Here, we conducted an exploratory study for label-free lung cancer pathology diagnosis and mapping of EGFR mutation spatial distribution using ambient mass spectrometry imaging (MSI).Materials and Methods: MSI analysis were performed in 55 post-operative non-small cell lung cancer (NSCLC) tumor and paired normal tissues to distinguish tumor from normal and classify pathology. We then compared diagnostic sensitivity of MSI and ADx-amplification refractory mutation system (ARMS) for the detection of EGFR mutation in pathological confirmed lung adenocarcinoma (AC) and explored EGFR mutations associated biomarkers to depict EGFR spatial distribution base on ambient MSI.Results: Of 55 pathological confirmed NSCLC, MSI achieved a diagnostic sensitivity of 85.2% (23/27) and 82.1% (23/28) for AC and squamous cell carcinoma (SCC), respectively. Among 27 AC, there were 17 EGFR-wild-type and 10 EGFR-mutated-positive samples detected by ARMS, and MSI achieved a diagnostic sensitivity of 82.3% (14/17) and 80% (8/10) for these two groups. Several phospholipids were specially enriched in AC compared with SCC tissues, with the higher ions intensity of phospholipids in EGFR-mutated-positive compared with EGFR-wild-type AC tissues. We also found EGFR mutations distribution was heterogeneous in different regions of same tumor by multi-regions ARMS detection, and only the regions with higher ions intensity of phospholipids were EGFR-mutated-positive.Conclusion: MSI method could accurately distinguish tumor pathology and subtypes, and phospholipids were reliable EGFR mutations associated biomarkers, phospholipids imaging could intuitively visualize EGFR mutations spatial distribution, may facilitate our understanding of tumor heterogeneity.

Post-transplant (post-Tx) kidney cancer has become the second-highest cause of death in kidney recipients. Late diagnosis and treatment are the main reasons for high mortality. Further research into early diagnosis and potential treatment is therefore required. In this current study, through genome-wide RNA-Seq profile analysis of post-Tx malignant blood samples and post-Tx non-malignant control blood samples (CTRL-Tx), we found Rap GTPase Interactor (RADIL) and Aprataxin (APTX) to be the most meaningful markers for cancer diagnosis. Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) of the RADIL-APTX signature model was 0.92 (P < 0.0001). Similarly, the AUC of RADIL alone was 0.91 (P < 0.0001) and that of APTX was 0.81 (P = 0.001). Additionally, using a semi-supervised method, we found that RADIL alone could better predict malignancies in kidney transplantation recipients than APTX alone. Kaplan-Meier analysis indicated that RADIL was expressed significantly higher in the early stages (I and II) of kidney, liver, stomach, and pancreatic cancer, suggesting the potential use of RADIL in early diagnosis. Multivariable Cox regression analysis found that RADIL together with other factors (including age, stage III, stage IV and CD8+ T cells) play a key role in kidney cancer development. Among those factors, RADIL could promote kidney cancer development (HR > 1, P < 0.05) while CD8+ T cells could inhibit kidney cancer development (HR < 1, P < 0.05). RADIL may be a new immunotherapy target for kidney cancer post kidney transplantation.

Background: Inactivation of microRNA-100 (miR-100) is involved in hepatocellular carcinoma (HCC) and miR-100 behaves as a tumor suppressor. To understand miR-100 function in HCC genesis and development in vivo, we developed hepatocyte-specific miR-100 deficient mice.Methods: Mice homozygous for floxed miR-100 allele that carried the Alb-Cre transgene (miR-100flox/floxAlb -Cre+) were developed by mating miR-100flox/flox mice with Alb-Cre+/+mice. The mice tails DNA were genotyped using the primers for LoxP sites and Cre recombinase, respectively. The specific deletion of miR-100 in the livers was verified by quantitative Real-time PCR (qRT-PCR). HE-staining was performed for histology analysis. Liver function was assessed by transaminase activity. The metabolic profiles of the hepatocytes were detected using a Seahorse XFe24 extracellular flux analyzer. The direct targets of miR-100 (such as IGF1R-β, mTOR and CDC25A) and HCC related protein (SHP-2) were detected by qRT-PCR and Western blot in liver tissues.Results: The resultant homozygous knockout mice with genotype of miR-100flox/flox-Alb-Cre+ showed an 80% decrease in hepatic miR-100 expression. In adult mice, miR-100 knockout has no effect on the liver function and morphology. In aged mice, HE staining showed that miR-100 knockout caused infiltration of inflammatory cells and expansion of hepatocellular nuclei. Consistently, liver function was impaired in miR-100 knockout aged mice as indicated by increased serum AST and ALT levels. The metabolic analysis demonstrated that the miR-100 knockout hepatocytes tend to adopt glycolysis. The expressions of the miR-100 target genes, such as IGF1R-β, CDC25A and mTOR, were increased. In addition, the known HCC related protein, SHP-2 also was up-regulated in the knockout livers.Conclusions: We successfully generated a miR-100 hepatocyte-specific knock-out mouse model. The malignant transformation related to HCC were observed in aged mice. Therefore, this model is suitable for investigating the mechanism of miR-100 inactivation contributing to HCC genesis in vivo.