Faced with the high heterogeneity and poor prognosis of colorectal cancer (CRC), this study sought to find new predictive prognostic strategies to improve the situation. Cuproptosis is a novel cell death mechanism that relies on copper regulation. However, the role of cuproptosis-related gene (CRG) in CRC remains to be elucidated. In this study, we comprehensively assessed the CRG landscape in CRC based on The Cancer Genome Atlas (TCGA). We identified differential expression and genetic alterations of CRG in CRC. CRG is highly correlated with initiation, progression, prognosis, and immune infiltration of CRC. We construct a risk score signature containing 3 CRGs based on LASSO. We explored the correlation of CRG-Score with clinicopathological features of CRC. Age, stage, and CRG-Score were integrated to construct a nomogram. The nomogram has robust predictive performance. We also understand the correlation of CRG-Score with CRC immune landscape. CRG-Score can effectively predict the immune landscape of CRC patients. Low-risk CRC patients have greater immunogenicity and higher immune checkpoint expression. Low-risk CRC patients may be better candidates for immunotherapy. At the same time, we also predicted more sensitive drugs in the high-risk CRC patients. In conclusion, the CRG risk score signature is a strong prognostic marker and may help provide new insights into the treatment of individuals with CRC.

Pylorus-preserving gastrectomy (PPG) is a function-preserving surgery for the treatment of early gastric cancer (EGC) in the middle third of the stomach. According to the literature reports, PPG decreases the incidence of dumping syndrome, bile reflux, gallstone formation, and nutritional deficit compared with conventional distal gastrectomy (CDG). However, the debates about PPG have been dominated by the incomplete lymphadenectomy and oncological safety. We carried out a systematic review and meta-analysis to evaluate the pathological and oncological outcomes of PPG. The protocol was registered in PROSPERO under number CRD42022304677. Databases including PubMed, Embase, Web of Science, and the Cochrane Register of Controlled Trials were searched before February 21, 2022. The outcomes included the pooled odds ratios (ORs) for dichotomous variables and weighted mean differences (WMDs) for continuous variables. For all outcomes, 95% confidence intervals (CIs) were calculated. Meta-analysis was performed using STATA software (Stata 14, Stata Corporation, Texas) and Review Manager 5.4. A total of 4500 patients from 16 studies were included. Compared with the CDG group, the PPG group had fewer lymph nodes harvested (WMD= −3.09; 95% CI −4.75 to −1.43; P < 0.001). Differences in the number of resected lymph nodes were observed at stations No. 5, No. 6, No. 9, and No. 11p. There were no differences in lymph node metastasis at each station. Shorter proximal resection margins (WMD = −0.554; 95% CI −0.999 to −0.108; P = 0.015) and distal resection margins (WMD = −1.569; 95% CI −3.132 to −0.007; P = 0.049) were observed in the PPG group. There were no significant differences in pathological T1a stage (OR = 0.99; 95% CI 0.80 to 1.23; P = 0.88), T1b stage (OR = 1.01; 95% CI 0.81 to 1.26; P = 0.88), N0 stage (OR = 0.97; 95% CI 0.63 to 1.48; P = 0.88), tumor size (WMD = −0.10; 95% CI −0.25 to 0.05; P = 0.187), differentiated carcinoma (OR = 1.04; 95% CI 0.74 to 1.47; P = 0.812) or signet ring cell carcinoma (OR = 1.22; 95% CI 0.90 to 1.64; P = 0.198). No significant differences were observed between the groups in terms of overall survival (HR = 0.63; 95% CI 0.24 to 1.67; P = 0.852) or recurrence-free survival (HR = 0.29; 95% CI 0.03 to 2.67; P = 0.900). The meta-analysis of existing evidence demonstrated that the survival outcomes of PPG may be comparable to those of CDG. However, fewer lymph nodes at stations in No. 5, No. 6, No. 9, and No. 11p were harvested with PPG. We also found shorter proximal resection margins and distal resection margins for PPG, meaning more remnant stomachs would be preserved in PPG.

Background: Despite breakthroughs in treatment, ovarian cancer (OC) remains one of the most lethal gynecological malignancies, with an increasing age-standardized mortality rate. This underscores an urgent need for novel biomarkers and therapeutic targets. Although growth factor receptor-bound protein 7 (GRB7) is implicated in cell signaling and tumorigenesis, its expression pattern and clinical implications in OC remain poorly characterized. Methods: To systematically investigate GRB7’s expression in OC, our study utilized extensive datasets from TCGA, GTEx, CCLE, and GEO. The prognostic significance of GRB7 was evaluated by means of Kaplan–Meier and Cox regression analyses. Using a correlation analysis and gene set enrichment analysis, relationships between GRB7’s expression and gene networks, immune cell infiltration and immunotherapy response were investigated. In vitro experiments were conducted to confirm GRB7’s function in the biology of OC. Results: Compared to normal tissues, OC tissues exhibited a substantial upregulation of GRB7. Reduced overall survival, disease-specific survival, and disease-free interval were all connected with high GRB7 mRNA levels. The network study demonstrated that GRB7 is involved in pathways relevant to the course of OC and has a positive connection with several key driver genes. Notably, GRB7’s expression was linked to the infiltration of M2 macrophage and altered response to immunotherapy. Data from single-cell RNA sequencing data across multiple cancer types indicated GRB7’s predominant expression in malignant cells. Moreover, OC cells with GRB7 deletion showed decreased proliferation and migration, as well as increased susceptibility to T cell-mediated cytotoxicity. Conclusion: With respect to OC, our results validated GRB7 as a viable prognostic biomarker and a promising therapeutic target, providing information about its function in tumorigenesis and immune modulation. GRB7’s preferential expression in malignant cells highlights its significance in the biology of cancer and bolsters the possibility that it could be useful in enhancing the effectiveness of immunotherapy.

The purpose of this study was to explore the prognostic value of Immunoscore in patients with early-onset colorectal cancer. We retrospectively analyzed 708 colorectal adenocarcinoma patients (2017–2020), ultimately including 36 early-onset colorectal cancer cases after exclusions. CD3+/CD8 + lymphocytes were quantified using immunohistochemistry and a self-trained neural network model from Cellpose 2.0. Immunoscore was calculated based on T cell densities in tumor cores and invasive margins, stratified as high or low. Prognostic associations were assessed via Kaplan-Meier analysis, Cox regression, and restricted cubic spline models. Results of Cox regression was validated by post-hoc analysis. Of all early-onset colorectal cancer patients, 23(63.9%) patients were graded as Immunoscore-high, 13(36.1%) were graded as Immunoscore-low. The self trained model achieved high consistency with manual counting. High Immunoscore correlated with earlier clinical stages (stage I/II: P = 0.011), reduced metastasis risk (N0, P = 0.042; M0, P = 0.009), and lower mortality (P = 0.009). Univariate Cox regression analysis identified Immunoscore as a possible predictor for overall survival (Hazard Ratio = 5.82, P = 0.030) and progression free survival (Hazard Ratio = 3.68, P = 0.014). The Post-hoc power analysis showed the type II error probability (β) of univariate Cox analysis for overall survival with a hazard ratio of 5.82 was 0.282 (28.2%), while for progression free survival with a hazard ratio of 3.68, β was 0.006 (0.6%). Restricted cubic spline showed that the influence of CD3+/CD8 + cells in different region on prognosis was not simply linear. Although Immunoscore didn’t remain statistically significant as an independent predictor of OS (Hazard Ratio = 4.76; P = 0.138) and PFS (Hazard Ratio = 1.83; P = 0.360) in multivariate Cox regression analysis, stratified Kapan-Meier curves by MMR status and clinical stage showed well separation. Immunoscore can serve as a possible indicator in predicting prognosis of patients with early-onset colorectal cancer, but still need large sample research validation.