Background KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. Methods 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. Results NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. Conclusions KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.

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Left- and right-sided colon cancer (LC and RC) differ substantially in their molecular characteristics and prognoses, and are thus treated using different strategies. We systematically analyzed alternative splicing (AS) events and splicing factors in LC and RC. RNA-seq data were used for genome-wide profiling of AS events that could distinguish LC from RC. The Exon Skip splicing pattern was more common in RC, while the Retained Intron pattern was more common in LC. The AS events that were upregulated in RC were enriched for genes in the axon guidance pathway, while those that were upregulated in LC were enriched for genes in immune-related pathways. Prognostic models based on differentially expressed AS events were built, and a prognostic signature based on these AS events performed well for risk stratification in colon cancer patients. A correlation network of differentially expressed AS events and differentially expressed splicing factors was constructed, and RBM25 was identified as the hub gene in the network. In conclusion, large differences in AS events may contribute to the phenotypic differences between LC and RC. The differentially expressed AS events reported herein could be used as biomarkers and treatment targets for colon cancer.

BackgroundCDCA7 is a copy number amplified gene identified not only in esophageal squamous cell carcinoma (ESCC) but also in various cancer types. Its clinical relevance and underlying mechanisms in ESCC have remained unknown.MethodsTissue microarray data was used to analyze its expression in 179 ESCC samples. The effects of CDCA7 on proliferation, colony formation, and cell cycle were tested in ESCC cells. Real-time PCR and Western blot were used to detect the expression of its target genes. Correlation of CDCA7 with its target genes in ESCC and various SCC types was analyzed using GSE53625 and TCGA data. The mechanism of CDCA7 was studied by chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay.ResultsThe overexpression of CDCA7 promoted proliferation, colony formation, and cell cycle in ESCC cells. CDCA7 affected the expression of cyclins in different cell phases. GSE53625 and TCGA data showed CCNA2 expression was positively correlated with CDCA7. The knockdown of CCNA2 reversed the malignant phenotype induced by CDCA7 overexpression. Furthermore, CDCA7 was found to directly bind to CCNA2, thus promoting its expression.ConclusionsOur results reveal a novel mechanism of CDCA7 that it may act as an oncogene by directly upregulating CCNA2 to facilitate tumor progression in ESCC.

Purpose: Vascular invasion (VI) is associated with recurrence and is an indicator of poor prognosis in gastric cancer (GC). Pre-operative identification of VI may guide the selection of the optimal surgical approach and assess the requirement for neoadjuvant therapy. Methods: A total of 271 patients were retrospectively collected and randomly allocated into the training and validation datasets. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features, and multivariable logistic regression analysis was used to develop the nomogram. Results: The nomogram consisted of pre-operative serum complement C3 levels, duration of symptoms, pre-operative computed tomography stage, abdominal distension and undifferentiated carcinoma. The nomogram provided good calibration for both the training and the validation set, with area under the curve values of 0.792 and 0.774. Decision curve analysis revealed that the nomogram was clinically useful. Conclusion: The present study constructed a nomogram for the pre-operative prediction of VI in patients with GC. The nomogram may aid the identification of high-risk patients and aid the optimization of pre-operative decision-making.

Background Pulmonary infection is one of the most common postoperative complications after radical gastrectomy for gastric cancer (GC) and is associated with a poorer prognosis. This study aimed to investigate potential predictive factors for pulmonary infection in elderly GC patients. Methods This study retrospectively enrolled 346 elderly GC patients undergoing elective radical gastrectomy between January 2017 and December 2020. Pulmonary infection within postoperative 30 days was set as the primary observational endpoint. The baseline demographic, clinicopathological, and laboratory data were compared between patients with or without pulmonary infection. ROC curves were plotted to evaluate the cut-off and predictive values of factors. Binary univariate and multivariate logistic regression analyses were employed to determine risk factors for postoperative pulmonary infection. Results Of the enrolled 346 patients, pulmonary infection was observed in 51 patients within postoperative 30 days, with an incidence of 14.7%. mFI was a significant predictor for pulmonary infection by ROC curve analysis (AUC: 0.770, P < 0.001). Moreover, preoperative mFI was the only independent risk factor for pulmonary infection (OR: 2.72, 95% CI: 2.02–3.31, P = 0.011) by univariate and multivariate logistic regression analyses. Conclusion Our study indicates that mFI independently predicts pulmonary infection in elderly GC patients.

Systemic inflammatory response (SIRS) can be used as a potential prognostic marker in patients with colorectal cancer (CRC). The purpose of this study was to examine the predictive role of the C-reactive protein (CRP)-lymphocyte ratio (CLR) in the prognosis of CRC. We retrospectively analyzed the data of CRC patients who underwent surgery from 2004 to 2019. The clinicopathological characteristics and follow-up records were analyzed. According to a cutoff value of CLR, the patients were divided into the high and low groups. Kaplan–Meier curves and Cox proportional hazards regression model were applied to assess the overall survival (OS). Clinicopathological characteristics analysis showed that gender, age, BMI, lymphocyte count, tumor location, left- and right-sided CRC, differentiation, T stage, M stage, TNM stage, carcinoembryonic antigen (CEA), CLR, CRP, and microsatellite status were found to differ significantly between the high and low CLR groups. Kaplan–Meier curves revealed that the high CLR group had a shorter OS, and the elderly or right-sided CRC patients faced a worse prognosis. Multivariate analysis suggested that age (hazard ratio [HR]:1.011, P = 0.003), differentiation (HR:1.331, P = 0.000), TNM stage (HR:2.425, P = 0.000), CEA (HR:1.001, P = 0.025), CLR (HR:1.261, P = 0.014) were significant independent prognostic factors for OS. Subgroup analysis demonstrated that females or patients not receiving postoperative adjuvant chemotherapy with high CLR might suffer a worse prognosis. Overall, CLR can be applied as a promising prognostic marker in CRC patients and has great potential in guiding clinical work.

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.