Because of the increased risk of gastric cancer in adults aged over 40 years in China, screening of this high-risk population is important.1 However, the financial burden of doing so would be high, ...because 45·2% of the population of China is aged over 40 years.
Background
The clinical values of inflammatory and nutritional markers remained unclear for gastric cancer with neoadjuvant chemotherapy (NACT).
Methods
The inflammatory, nutritional markers and ...their changes were analyzed for locally advanced gastric cancer with NACT. The predictive value was evaluated by the Cox proportional hazards regressions under three hypothesized scenarios. The nomograms including independent prognostic factors were plotted for survival prediction.
Results
A total of 225 patients were included in the study. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index, and hemoglobin (Hgb) were significantly reduced, and the body mass index was significantly increased after NACT (all
P
< 0.05). The pre-NACT NLR hazard ratio (HR) = 1.176,
P
= 0.059 showed a trend to correlate with the overall survival (OS) when only pre-NACT markers available; The post-NACT Hgb (HR = 0.982,
P
= 0.015) was the independent prognostic factor when only post-NACT markers available; The post-NACT Hgb (HR = 0.984,
P
= 0.025) and the change value of LMR (HR = 1.183,
P
= 0.036) were the independent prognostic factors when both pre- and post-NACT markers available. The nomogram had a similar Harrell’s C-statistic compared to ypTNM stage (0.719 vs. 0.706).
Conclusion
For locally advanced gastric cancer, the NACT could significantly decrease some inflammatory markers. The pre-NACT NLR, the post-NACT Hgb and the change value of LMR had some values in survival prediction combined with age, sex, tumor location and the clinical stages under different clinical scenarios. The elevated initial NLR, the preoperative anemia and the greater change value of LMR implied a poor prognosis.
Background
Traditional diagnosis methods for lymph node metastases are labor-intensive and time-consuming. As a result, diagnostic systems based on deep learning (DL) algorithms have become a hot ...topic. However, current research lacks testing with sufficient data to verify performance. The aim of this study was to develop and test a deep learning system capable of identifying lymph node metastases.
Methods
921 whole-slide images of lymph nodes were divided into two cohorts: training and testing. For lymph node quantification, we combined Faster RCNN and DeepLab as a cascade DL algorithm to detect regions of interest. For metastatic cancer identification, we fused Xception and DenseNet-121 models and extracted features. Prospective testing to verify the performance of the diagnostic system was performed using 327 unlabeled images. We further validated the proposed system using Positive Predictive Value (PPV) and Negative Predictive Value (NPV) criteria.
Results
We developed a DL-based system capable of automated quantification and identification of metastatic lymph nodes. The accuracy of lymph node quantification was shown to be 97.13%. The PPV of the combined Xception and DenseNet-121 model was 93.53%, and the NPV was 97.99%. Our experimental results show that the differentiation level of metastatic cancer affects the recognition performance.
Conclusions
The diagnostic system we established reached a high level of efficiency and accuracy of lymph node diagnosis. This system could potentially be implemented into clinical workflow to assist pathologists in making a preliminary screening for lymph node metastases in gastric cancer patients.
Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs (ncRNAs) widely expressed in eukaryotic cells. Mounting evidence has highlighted circRNAs as critical regulators of various ...tumours. More importantly, circRNAs have been revealed to recruit and reprogram key components involved in the tumour microenvironment (TME), and mediate various signaling pathways, thus affecting tumourigenesis, angiogenesis, immune response, and metastatic progression. In this review, we briefly introduce the biogenesis, characteristics and classification of circRNAs, and describe various mechanistic models of circRNAs. Further, we provide the first systematic overview of the interplay between circRNAs and cellular/non-cellular counterparts of the TME and highlight the potential of circRNAs as prospective biomarkers or targets in cancer clinics. Finally, we discuss the biological mechanisms through which the circRNAs drive development of resistance, revealing the mystery of circRNAs in drug resistance of tumours.
Deep understanding the emerging role of circRNAs and their involvements in the TME may provide potential biomarkers and therapeutic targets for cancer patients. The combined targeting of circRNAs and co-activated components in the TME may achieve higher therapeutic efficiency and become a new mode of tumour therapy in the future.
Summary Background D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient ...outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II–IIIB gastric cancer. Methods The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II–IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m2 twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m2 on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov ( NCT00411229 ). Findings 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4–41·7) in the chemotherapy and surgery group and 34·3 months (25·6–41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69–79) in the chemotherapy and surgery group and 59% (53–64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44–0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). Interpretation Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. Funding F Hoffmann-La Roche and Sanofi-Aventis.
Objectives
Long non‐coding RNAs (lncRNAs) are key mediators in various malignancies. Linc01503 was previously elucidated to promote gastric cancer (GC) cell invasion. However, the upstream mechanism ...of linc01503 and its involvement in GC cell cycle, apoptosis and tumorigenesis still remain unclear.
Materials and Methods
Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction (qRT‐PCR) assays were implicated to detect linc01503 level in GC. The role of linc01503 was detected by in vitro functional assays and in vivo xenograft tumour models. The association between linc01503 and its upstream effector was identified by chromatin immunoprecipitation (ChIP) assays. The mechanistic model of linc01503 was clarified using subcellular separation, fluorescence in situ hybridization, RNA‐sequencing, RNA immunoprecipitation (RIP) and ChIP assays.
Results
Linc01503 was remarkably elevated in GC and tightly linked with the overall survival of patients with GC. The key transcription factor early growth response protein 1 (EGR1) critically activated the transcription of linc01503. Functionally, linc01503 knockdown resulted in the activation of apoptosis and G1/G0 phase arrest in GC. Mechanistically, linc01503 interacted with histone modification enzyme enhancer of zeste 2 (EZH2) and lysine (K)‐specific demethylase 1A (LSD1), thereby mediating the transcriptional silencing of dual‐specificity phosphatase 5 (DUSP5) and cyclin‐dependent kinase inhibitor 1A (CDKN1A) in GC.
Conclusions
EGR1‐activated linc01503 could epigenetically silence DUSP5/CDKN1A expression to mediate cell cycle progression and tumorigenesis, implicating it as a prospective target for GC therapeutics.
The EGR1‐activated lncRNA linc01503 mediated gastric carcinogenesis through the axis of EZH2/LSD1/DUSP5/CDKN1A. The mechanistic model of linc01503 is a further prerequisite for progress in translational exploitation of lncRNAs for treatment of patients with GC.
Gastric cancer (GC) is a global health problem, with more than 1 million people newly diagnosed with GC worldwide each year. GC is more prevalent in less developed countries than in more developed ...countries. About half of all GC cases worldwide occur in East Asia, notably China. Globally, overall incidence rates of GC are declining, which is potentially attributed to a decrease in
(
) infection and the use of refrigeration to preserve foods rather than salt. GC is a multifactorial disease, and its occurrence and development were impacted by environmental and genetic factors.
infection is the primary risk factor for GC, especially for non-cardia. The prognosis of GC is poor due to stages at the first diagnosis. The 5-year survival rate is less than 10% when patients are diagnosed at an advanced stage, but the rate is as high as 85% if patients are detected at an earlier stage. Endoscopic screening can potentially prevent GC by early diagnosis and early treatment and has been widely adopted in screening programs in East Asian countries, such as Japan and Korea. This review summarizes updated epidemiological aspects, risk factors, and prevention strategies of GC in recent years to help researchers determine the most effective intervention strategies for reducing risk of GC.
Abstract
Protein–protein interactions (PPIs) are crucial to mediate biological functions, and understanding PPIs in cancer type-specific context could help decipher the underlying molecular ...mechanisms of tumorigenesis and identify potential therapeutic options. Therefore, we update the Protein Interaction Network Analysis (PINA) platform to version 3.0, to integrate the unified human interactome with RNA-seq transcriptomes and mass spectrometry-based proteomes across tens of cancer types. A number of new analytical utilities were developed to help characterize the cancer context for a PPI network, which includes inferring proteins with expression specificity and identifying candidate prognosis biomarkers, putative cancer drivers, and therapeutic targets for a specific cancer type; as well as identifying pairs of co-expressing interacting proteins across cancer types. Furthermore, a brand-new web interface has been designed to integrate these new utilities within an interactive network visualization environment, which allows users to quickly and comprehensively investigate the roles of human interacting proteins in a cancer type-specific context. PINA is freely available at https://omics.bjcancer.org/pina/.
Graphical Abstract
Graphical Abstract
A schematic overview of PINA 3.0.
Identification of effective prognostic biomarkers and targets are of crucial importance to the management of estrogen receptor positive (ER+) breast cancer. CCNA2 (also known as CyclinA2) belongs to ...the highly conserved cyclin family and is significantly overexpressed in various cancer types. In this study, we demonstrated that CCNA2 had significant predictive power in distant metastasis free survival, disease free survival, recurrence free survival and overall survival of ER+ breast cancer patients. We also found that CCNA2 was closely associated with tamoxifen resistance. In addition, gene set enrichment analysis (GSEA) revealed that its expression was positively associated with genes overexpressed in endocrine therapy resistant samples. Finally, though CCNA2-Drug interaction network, we demonstrated the interactions between CCNA2 and several available cancer drugs. Overall, we suggest that CCNA2 is a biomarker for the prognosis of ER+ breast cancer and monitoring of tamoxifen efficacy. It's also a promising target for developing new strategies to prevent or even reverse tamoxifen resistance. Moreover, CCNA2 expression may help monitoring tamoxifen efficacy and directing personalized therapies. Nevertheless, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed before its application in clinical settings.
Cancer cells subvert immune surveillance through inhibition of T cell effector function. Elucidation of the mechanism of T cell dysfunction is therefore central to cancer immunotherapy. Here, we ...report that dual specificity phosphatase 2 (DUSP2; also known as phosphatase of activated cells 1, PAC1) acts as an immune checkpoint in T cell antitumor immunity. PAC1 is selectively upregulated in exhausted tumor-infiltrating lymphocytes and is associated with poor prognosis of patients with cancer. PAC1
effector T cells lose their proliferative and effector capacities and convert into exhausted T cells. Deletion of PAC1 enhances immune responses and reduces cancer susceptibility in mice. Through activation of EGR1, excessive reactive oxygen species in the tumor microenvironment induce expression of PAC1, which recruits the Mi-2β nucleosome-remodeling and histone-deacetylase complex, eventually leading to chromatin remodeling of effector T cells. Our study demonstrates that PAC1 is an epigenetic immune regulator and highlights the importance of targeting PAC1 in cancer immunotherapy.
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