BACKGROUND: Interferon regulatory factor 1 (IRF1) plays a crucial role in the type I interferon (IFN) response. However, its functional role and underlying mechanisms in gastric cancer (GC) remain unclear. This study aims to investigate the biological significance of IRF1 in GC progression and its potential as a therapeutic target. METHODS: IRF1 expression was analyzed using The Cancer Genome Atlas (TCGA) and GTEx databases, validated by immunohistochemistry (IHC) in 366 GC patients. Functional experiments, including CCK-8, Transwell migration and invasion assays, and apoptosis analysis, were conducted in GC cell lines with IRF1 overexpression or knockdown. A subcutaneous xenograft model was established to evaluate the in vivo effects of IRF1 on tumor growth. Co-immunoprecipitation and western blotting were performed to explore the molecular interactions between IRF1 and Myxovirus resistance 2 (MX2), as well as its regulation of the PI3K signaling pathway. RESULTS: IRF1 expression was significantly higher in gastric cancer tissues than in adjacent normal tissues. Higher IRF1 levels were also associated with improved patient survival. Overexpression of IRF1 inhibited GC cell proliferation, migration, and invasion while promoting apoptosis, whereas IRF1 knockdown had the opposite effects. Mechanistically, IRF1 suppressed PI3K/p-AKT signaling while enhancing p-ERK1/2 activation. Moreover, IRF1 directly interacted with MX2, a protein involved in epithelial-mesenchymal transition (EMT), and this interaction was essential for suppressing MX2-mediated oncogenic activity. In vivo experiments confirmed that IRF1 overexpression significantly reduced tumor growth and metastasis. CONCLUSIONS: IRF1 functions as a tumor suppressor in GC by modulating the PI3K signaling pathway and interacting with MX2 to inhibit EMT. These findings highlight IRF1 as a potential therapeutic target for GC treatment.

Clinical evidence reveals that Fusobacterium nucleatum (F. nucleatum) colonization and stromal barriers synergistically suppress T cell infiltration, limiting the efficacy of colorectal cancer (CRC) immunotherapy and highlighting the need for a closed-loop strategy to restore antitumor immunity. Here, we present a bio-responsive co-assembled polymeric micelles (CPM-GalNAc) for targeted co-delivery of calcipotriol (Cal) and ornidazole (ONZ), designed to achieve closed-loop immune modulation by simultaneously remodeling the extracellular matrix (ECM) and eradicating intratumor bacteria. Notably, Cal and ONZ were covalently linked via disulfide bonds to form a conjugate (Cal-ONZ), which significantly improved drug encapsulation efficiency compared to individual drug loading. This system employs a dual-lock design: poly(β-amino ester) hydrophobic microdomains undergo hydrophilic-hydrophobic transition in the mildly acidic tumor microenvironment, exposing GalNAc moieties for specific recognition of F. nucleatum. Elevated glutathione levels trigger selective release of ONZ and Cal, where ONZ eliminates F. nucleatum to enhance cytotoxic T cell recruitment through pathogen-associated molecular patterns, while Cal concurrently suppresses cancer-associated fibroblasts and disrupts the ECM, thereby facilitating deeper T cell infiltration. This approach robustly enhances antitumor immune responses, augments the efficacy of αPD-L1 checkpoint blockade, and establishes durable immune memory to prevent recurrence, offering a promising strategy for reinforced CRC immunotherapy.

Background Most gastric cancer (GC) patients receive uniform treatment due to the lack of predictive biomarkers for chemotherapy or radiotherapy. We previously identified epithelial-mesenchymal transition (EMT) and metabolism subgroups in GC cell lines based on kinomic profiles, but their clinical relevance was unknown. Methods We developed an ensemble model using 37 kinases that differed between cell line subgroups to classify stage II-IV GC into EMT and metabolism subgroups. Survival differences between those who received chemotherapy or radiotherapy and those who did not were compared within each subgroup to validate the model effectiveness in predicting therapeutic response. An iteration approach was further applied to optimise and validate the feature set via multiple publicly-available datasets. Findings An 11-kinase signature stratified 893 patients into two subgroups. The metabolism subgroup showed significantly better survival with chemotherapy (HRmultivariable = 0.56) and radiotherapy (HRmultivariable = 0.55), whereas no such improvement was observed in the EMT subgroup. Significant interaction between kinomic subgroups and treatments were noted. The chemotherapy benefits between subgroups were greater with 5-fluorouracil-based regimens than cisplatin-based ones. This kinomic taxonomy was distinct from Lauren classification and previous transcriptomic subtypes and also suggested differential therapeutic vulnerabilities between subgroups. Interpretation This model holds promise for optimising chemotherapy and radiotherapy decisions for GC. Funding Biomedicine Discovery Scholarship and Graduate Research Completion Award, Monash University; National Natural Science Foundation of China (81602165) (C.H.). Australian Research Council Centre of Excellence for the Mathematical Analysis of Cellular Systems (CE230100001) (L.K.N.).

Epstein-Barr virus-associated gastric cancer (EBVaGC) is a unique subtype of gastric cancer (GC) with distinct molecular characteristics that generally has a better prognosis. BamHI-A leftward frame 4 (BALF4), an envelope glycoprotein encoded by the Epstein-Barr virus (EBV), plays an important role in EBV infection. However, its biological function and potential molecular mechanisms in EBVaGC remain unclear. This study aimed to investigate the impact of the highly expressed viral gene BALF4 on the progression of EBVaGC. Here, we detected the expression of BALF4 in GC tissue chips and validated that the presence of BALF4 might be associated with a favorable prognosis in EBVaGC. The results showed that BALF4 inhibited the proliferation, migration, and invasion of GC cells in vitro and in vivo. In addition, we discovered that BALF4 interacts with N-acetyltransferase 10 (NAT10). High expression of NAT10 in GC tissues promotes the malignant phenotype of GC cells. We discovered that BALF4 could inhibit the malignant progression of GC by promoting the ubiquitination and degradation of NAT10. In summary, our study revealed a possible mechanism explaining the favorable prognosis of the EBVaGC subtype, which contributes to a better understanding of this special type of GC.

Infectious diseases caused by pathogenic microorganisms and tumors arising from uncontrolled cell proliferation can be intricately linked through the lens of viromics. This study aimed to delineate the landscape of viral infections in gastric cancer, focusing on the relationship between pathogenic microorganisms and tumorigenesis. By conducting transcriptomic sequencing of gastric cancer tissues, we identified gastric cancer-associated viruses from raw transcriptomic data. This methodology was validated using public databases and experimental evidence, ensuring the authenticity of viral detection. Single-cell data further identified specific cells harboring these viruses and elucidated the correlation between viral gene expression and the genesis and progression of gastric cancer. Common tumor viruses, such as human endogenous retrovirus (HERV), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV), along with unique DNA viruses and bacteriophages, were detected in gastric cancer. Additionally, these viruses have been detected in both tumor and immune cells, indicating a close association between viral gene expression and the development of gastric cancer. This study advances the technique of screening viruses from transcriptomes, charting the distribution of viruses within tumors, clarifying the interplay between viruses and cancer, and identifying previously unknown viruses related to the occurrence and progression of cancer.IMPORTANCEIn our study, we have carefully examined the viral landscape in gastric cancer, supported by a series of thorough experiments that verify its reliability. Our approach has not only confirmed the presence of viruses known to be associated with cancer development but also identified a range of additional viral entities, including human cytomegalovirus (HCMV) and various herpesviruses, along with numerous bacteriophages. The high incidence of these viruses within tumor samples suggests they could be considered as potential biomarkers for early cancer detection. This method enhances our understanding of the role viruses play in cancer, which may assist scientists and medical professionals in identifying viral presence in cancers and could offer new angles for cancer prevention and the development of related measures. By identifying specific viruses linked to different cancers, we aim to improve patient outcomes.

NSUN2, a major methyltransferase that catalyzes m5C methylation in eukaryotes, is known to be implicated in the development of multiple cancers. However, its role in colorectal cancer (CRC) and the related molecular mechanisms have yet to be sufficiently determined. Here, we conducted an analysis of public database (722 CRC patients) and two distinct cohorts from our centre (1559 CRC patients), which revealed that NSUN2 is upregulated in CRC and correlates with unfavourable prognosis. Our analyses also showed that NSUN2 promotes the proliferation and metastasis capabilities of CRC cells. Intriguingly, NSUN2 was found to promote CRC via an m5C-independent mechanism, which has not been previously reported. Overexpression of both wild-type and m5C enzymatic-dead mutant NSUN2 upregulated and activated the ErbB-STAT3 signalling pathway. We also found that both wild-type and the m5C enzymatic-dead mutant NSUN2 closely interacted with CUL4B. Silencing of CUL4B effectively inhibited the m5C-independent function of NSUN2. Moreover, overexpression of NSUN2 enhanced the sensitivity of CRC cells to lapatinib. Taken together, our findings revealed a novel m5C-independent mechanism for NSUN2 in the malignancy and lapatinib sensitivity of CRC via activation of the CUL4B/ErbB-STAT3 pathway, which provides a potential therapeutic strategy for patients with CRC. HIGHLIGHTS: NSUN2 is upregulated in CRC and associated with poor prognosis of CRC patients. NSUN2 promotes CRC malignancy independently of its m5C-enzymatic activity, a mechanism that has not been previously reported. The non-m5C carcinogenic roles of NSUN2 may be mediated through interactions with CUL4B, thereby activating the ErbB-STAT3 signalling pathway. NSUN2-mediated upregulation of ErbB-STAT3 pathway enhances the sensitivity of CRC to lapatinib treatment.

Alternative splicing is a pivotal regulatory mechanism in cellular biology that critically influences the tumorigenesis, progression, and phenotypic diversity of cancer. This study aimed to assess the intricate details and regulatory mechanisms of alternative splicing in gastric cancer. We constructed a comprehensive map of aberrant alternative splicing events in gastric cancer through bioinformatic analysis of public databases and clinical samples. Our study identified many abnormal splicing events in gastric cancer tissues, with exon skipping being the most frequent event. SNRPB, a key spliceosome component and principal splicing factor, was associated with the aberrant splicing of numerous splicing factors and oncogenes, influencing the p53 signaling pathway in the development and progression of gastric cancer. SNRPB directly regulates the selective splicing of TP53 by modulating its downstream factor, PUF60, thus facilitating the initiation and progression of gastric cancer. Therefore, SNRPB overexpression is linked to poor prognosis in gastric cancer and is a potential biomarker and therapeutic target.

BACKGROUND:Muscle-specific strength is a newly proposed indicator for assessing muscle quality. Its prognostic value in patients undergoing cancer surgery remains unclear. This study aims to evaluate the impact of low muscle-specific strength on short- and long-term outcomes in patients with resectable gastric cancer. METHODS:Patient data were prospectively collected from 2013 to 2019 for individuals diagnosed with gastric cancer. Muscle-specific strength was determined by calculating the ratio of grip strength to skeletal muscle area. Reference values for low muscle-specific strength were calculated using optimal stratification with X-tile software. Survival outcomes were analyzed using Kaplan-Meier survival curves and multivariate Cox proportional hazards models. RESULTS:A total of 1404 patients were included, comprising 1030 males (73.4 %) and 374 females (26.6 %) with a median age of 66 years. Low muscle-specific strength was identified as an independent risk factor for severe postoperative complications (OR = 2.026, 95 % CI = 1.115-3.684, P = 0.021) and overall survival (HR = 1.385, 95 % CI = 1.072-1.789, P = 0.013). In the subgroup analysis, low muscle-specific strength emerged as an independent risk factor for both postoperative severe complications (HR = 1.938, 95 % CI = 1.024-3.668, P = 0.042) and overall survival (HR = 1.359, 95 % CI = 1.017-1.816, P = 0.038) in males, but not in females. A combination of low muscle strength, low muscle-specific strength, and low muscle mass exhibited a better prognostic value for mortality risk than any two-factor combination or individual indicator. CONCLUSIONS:Muscle-specific strength may serve as a reliable alternative to traditional sarcopenia criteria in predicting the prognosis of surgical oncology patients. The integration of multiple muscle-related indicators can further enhance risk stratification for adverse outcomes.

Lymph node metastasis (LNM) represents the predominant metastatic pathway and a critical prognostic determinant in gastric adenocarcinoma. Accurate preoperative prediction of LNM status is imperative for optimizing tumor staging, therapeutic decision-making, and prognostic evaluation. This study aims to develop and validate a radiomics model utilizing contrast-enhanced computed tomography (CT) features from both tumor and stomach regions for preoperative assessment of LNM status. A retrospective analysis was performed on 279 patients who underwent radical gastrectomy, randomly divided into a training cohort (n = 195) and a validation cohort (n = 84). Preoperative contrast-enhanced abdominal CT images were collected, and radiomics features were extracted from both the tumor and stomach. After Z-score normalization, feature selection was conducted using inter- and intra-class correlation, univariate analysis, and LASSO regression. Six machine learning algorithms were used to construct radiomics models based on tumor, stomach, and their combination. Each model was trained using five-fold cross-validation, and their performance was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). Univariate analysis and logistic regression were performed to identify significant clinical features, leading to the development of a combined model incorporating both clinical and radiomics features. A total of 12 radiomics features were selected to construct the tumor - stomach wall radiomics model. Among the six algorithms, the LightGBM-based model demonstrated superior performance, achieving an AUC of 0.899 (95

BACKGROUND:The newly released Asian Working Group for Cachexia (AWGC) criteria share similar diagnostic items with the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study aims to compare the AWGC cachexia and GLIM malnutrition in patients with gastric cancer and investigate whether one diagnosis continues to be a prognostic factor in individuals diagnosed with the other condition. METHODS:Data of patients who underwent radical gastrectomy for gastric adenocarcinoma were prospectively collected from 2013 to 2019. The AWGC and GLIM criteria were applied to diagnosis cachexia and malnutrition, respectively. Univariate and multivariate logistic and Cox regression were used to verify the effect of relevant factors on postoperative complications and overall survival. RESULTS:A total of 1420 patients were included, among whom 174 (12.3 %) were diagnosed with AWGC-cachexia alone, 85 (6.0 %) were diagnosed with GLIM-malnutrition alone, and 324 (22.8 %) had both AWGC-cachexia and GLIM-malnutrition. Both AWGC-cachexia and GLIM-malnutrition were independent risk factors for complications and overall survival. When they coexisted, the odds ratios (OR) and hazard ratios (HR) tended to be higher. In the AWGC-cachexia subset, GLIM-malnutrition remained an independent risk factor (HR = 1.544, 95 % CI = 1.098-2.171, P = 0.012) for overall survival after the adjustment of confounding factors. Similarly, in the GLIM-malnutrition subset, AWGC-cachexia remained an independent risk factor for overall survival (HR = 1.697, 95 % CI = 1.087-2.650, P = 0.020). Patients with both cachexia and malnutrition had the worst overall survival. CONCLUSION:AWGC-cachexia and GLIM-malnutrition criteria were two non-redundancy tools in reflecting mortality risk in preoperative nutritional assessment.

Background Cell adhesion molecules (CAMs) play a vital role in cell-cell interactions, immune response modulation, and tumor cell migration. However, the unique role of CAMs in gastric cancer (GC) remains largely unexplored. Methods This study characterized the genetic alterations and mRNA expression of CAMs. The role of CD34, a representative molecule, was validated in 375 GC tissues. The activity of the CAM pathway was further tested using single-cell and bulk characterization. Next, data from 839 patients with GC from three cohorts was analyzed using univariate Cox and random survival forest methods to develop and validate a CAM-related prognostic model. Results Most CAM-related genes exhibited multi-omics alterations and were associated with clinical outcomes. There was a strong correlation between increased CD34 expression and advanced clinical staging (P = 0.026), extensive vascular infiltration (P = 0.003), and unfavorable prognosis (Log-rank P = 0.022). CD34 expression was also found to be associated with postoperative chemotherapy and tumor immunotherapy response. Furthermore, the CAM pathway was significantly activated and mediated poor prognosis. Additionally, eight prognostic signature genes (PSGs) were identified in the training cohort. There was a substantial upregulation of the expression of immune checkpoints and a pronounced infiltration of immune cells in GC tissues with high PSG score, which is consistent with the prediction of increased sensitivity to immunotherapy. Moreover, 9 compounds from the CTRPv2 database and 13 from the Profiling Relative Inhibition Simultaneously in Mixture (PRISM) database were identified as potential therapeutic drugs for patients with GC with high PSG score. Conclusion Thorough understanding of CAM pathways regulation and the innovative PSG score model hold significant implications for medical diagnosis, potentially enhancing personalized treatment strategies and improving patient outcomes in GC management.

BACKGROUND:This study aimed to investigate perioperative body composition changes and their clinical implications in patients undergoing radical gastric cancer surgery. METHODS:Patient data are prospectively collected. Computed tomography scans were conducted within 30 days preoperatively and on the seventh postoperative day to assess skeletal muscle mass index (SMI), skeletal muscle density (SMD), and subcutaneous adipose tissue (SAT). Changes in these parameters between the 2 scans were quantified. Logistic regression analysis was used to determine factors influencing body composition loss and clinical outcomes. RESULTS:A total of 335 patients were included, showing varying degrees of decline in SMI, SMD, and SAT during the perioperative period. Multivariate analysis identified age ≥65 and low handgrip strength as independent risk factors for excessive SMI loss, whereas laparoscopic surgery served as a protective factor. For excessive SMD loss, independent risk factors included preoperative low SMD, Nutritional Risk Screening 2002 score ≥3, and hypoalbuminemia. Moreover, age ≥65 was identified as an independent risk factor for excessive SAT loss, whereas laparoscopic surgery remained protective. Excessive SMI and SMD loss are correlated with increased postoperative complications, prolonged hospital stays, and higher costs. Both excessive losses in SMI and SMD are independently associated with the incidence of postoperative complications. Further analysis revealed that excessive SMD loss (odds ratio, 3.164; 95% CI, 1.214-8.243) independently contributed to readmission risk. CONCLUSION:Excessive SMI and SMD loss are associated with adverse clinical outcomes. It is essential to address and improve preoperative modifiable risk factors to reduce perioperative muscle loss and enhance prognosis.

Background Survival prognosis of patients with gastric cancer (GC) often influences physicians' choice of their follow-up treatment. This study aimed to develop a positron emission tomography (PET)-based radiomics model combined with clinical tumor-node-metastasis (TNM) staging to predict overall survival (OS) in patients with GC. Methods We reviewed the clinical information of a total of 327 patients with pathological confirmation of GC undergoing 18 F-fluorodeoxyglucose (18 F-FDG) PET scans. The patients were randomly classified into training (n = 229) and validation (n = 98) cohorts. We extracted 171 PET radiomics features from the PET images and determined the PET radiomics scores (RS) using the least absolute shrinkage and selection operator (LASSO) and random survival forest (RSF). A radiomics model, including PET RS and clinical TNM staging, was constructed to predict the OS of patients with GC. This model was evaluated for discrimination, calibration, and clinical usefulness. Results On multivariate COX regression analysis, the difference between age, carcinoembryonic antigen (CEA), clinical TNM, and PET RS in GC patients was statistically significant (p < 0.05). A radiomics model was developed based on the results of COX regression. The model had the Harrell's concordance index (C-index) of 0.817 in the training cohort and 0.707 in the validation cohort and performed better than a single clinical model and a model with clinical features combined with clinical TNM staging. Further analyses showed higher PET RS in patients who were older (p < 0.001) and those who had elevated CEA (p < 0.001) and higher clinical TNM (p < 0.001). At different clinical TNM stages, a higher PET RS was associated with a worse survival prognosis. Conclusions Radiomics models based on PET RS, clinical TNM, and clinical features may provide new tools for predicting OS in patients with GC.

Molecular residual disease (MRD), detected by circulating tumor DNA (ctDNA) can be involved in the entire process of solid tumor management, including recurrence prediction, efficacy evaluation, and risk stratification. Currently, the detection technologies are divided into two main categories, as follows: tumor-agnostic and tumor informed. Tumor-informed assay obtains mutation information by sequencing tumor tissue samples before blood MRD monitoring, followed by formulation of a personalized MRD panel. Tumor-agnostic assays are carried out using a fixed panel without the mutation information from primary tumor tissue. The choice of testing strategy may depend on the level of evidence from ongoing randomized clinical trials, investigator preference, cost-effectiveness, patient economics, and availability of tumor tissue. The review describes the difference between tumor informed and tumor agnostic detection. In addition, the clinical application of ctDNA MRD in solid tumors was introduced, with emphasis on lung cancer, colorectal cancer, Urinary system cancer, and breast cancer.

Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.

目的:研究甲基转移酶样因子3(METTL3)在结肠癌患者中的表达特征及其与临床预后相关性,并探讨METTL3表达对结肠癌细胞不同生物学表型的影响.方法:综合分析癌症基因组图谱计划(TCGA)数据库和4个不同来源的基因表达数据库(GE0)数据集中1 278例结肠癌组织和41例癌旁组织中METTL3基因的表达差异;使用Kaplan-Meier曲线分析METTL3表达高低对患者预后的影响.回顾性收集2014-2018年温州医科大学附属第一医院行根治性手术的481例结肠癌组织和59例癌旁组织,使用免疫组化法检测METTL3蛋白的表达差异.采用小干扰RNA(siRNA)分别敲低结肠癌细胞系DLD-1和HCT-116中METTL3的表达水平;采用CCK-8法和Transwell法检测METTL3表达对结肠癌细胞系不同恶性表型的影响.结果:在TCGA数据库和本中心结肠癌组织标本中,METTL3在肠癌组织中的表达均升高(P＜0.001).生存分析结果显示,METTL3高表达与结肠癌患者较短的总生存期(Log-rank P=0.028)和无病生存期(Log-rank P=0.035)相关.单因素和多因素Cox分析结果显示,METTL3可以作为结肠癌患者预后的独立危险因素(HR=1.335,95％CI=1.032～1.738,P=0.030).同时,敲低METTL3的表达可以显著抑制结肠癌细胞DLD-1和HCT-116的增殖(P＜0.01)和迁移侵袭能力(P＜0.01).结论:METTL3在结肠癌组织中表达上调,并可以作为结肠癌患者不良预后的独立因素.敲低METTL3表达可以抑制结肠癌细胞恶性表型.METTL3可能作为致癌基因参与结肠癌恶性进展.

Background:Elderly people and patients with colorectal cancer (CRC) are both at high risk of malnutrition. Therefore, it is of great significance to explore suitable malnutrition screening and diagnostic indicators for elderly patients with CRC. Recently, the Global Leadership Initiative on Malnutrition (GLIM) proposed new diagnostic criteria for malnutrition. The aim of this article was to evaluate the diagnostic value of GLIM criteria for malnutrition in elderly colorectal patients. We explored the relationship between GLIM-malnutrition, post-operative complications and the long-term prognosis of elderly colorectal patients. Methods:Elderly patients (aged ≥65 years) who underwent CRC surgery from January 2015 to December 2018 were included. Malnutrition was diagnosed based on the GLIM criteria. The relationships between GLIM-malnutrition and clinical characteristics were analyzed by t-tests, Mann-Whitney U tests, and chi-squared tests. The relationships between GLIM-malnutrition and post-operative complications were analyzed by chi-squared tests, and logistic regression analyses. The relationships between GLIM-malnutrition and the long-term prognosis were analyzed by Kaplan-Meier analyses and logistic and Cox regression analyses. Results:A total of 385 elderly patients were included in this study, and 118 patients (30.65%) were diagnosed with malnutrition according to the GLIM criteria. GLIM-malnutrition was significantly associated with older age, lower body mass index (BMI), lower grip strength, tumor location, higher Nutrition Risk Screening 2002 (NRS-2002), and lower levels of albumin and hemoglobin. GLIM-malnutrition was an independent risk factor [odds ratio (OR): 1.753, 95% confidence interval (CI): 1.100-2.795, P=0.018] for post-operative complications. Cox regression analysis showed that GLIM-malnutrition was an independent risk factor for overall survival in elderly patients with CRC. Conclusions:The GLIM criteria are feasible diagnostic criteria for malnutrition of elderly patients with CRC. GLIM-malnutrition is significantly associated with post-operative complications and overall survival in elderly patients with CRC.

Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.

The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.