A bioinformatics approach to identify a disulfidptosis-related gene signature for prognostic implication in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a type of cancer that arises from the glandular epithelial cells that produce mucus in the colon. COAD is influenced by various factors, including genetics, environment and lifestyle. The outcome of COAD is determined by the tumor stage, location, molecular characteristics and treatment. Disulfidptosis is a new mode of cell death that may affect cancer development. We discovered genes associated with disulfidptosis in colon adenocarcinoma and proposed them as novel biomarkers and therapeutic targets for COAD. We analyzed the mRNA expression data and clinical information of COAD patients from The Cancer Genome Atlas (TCGA) database and Xena databases, extracted disulfidptosis-related genes from the latest reports on disulfidptosis. We used machine learning to select key features and build a signature and validated the risk model using data from the Gene Expression Omnibus (GEO) database and Human Protein Atlas (HPA). We also explored the potential biological functions and therapeutic implications of the disulfidptosis-related genes using CIBERSORTx and GDSC2 databases. We identified four disulfidptosis-related genes: TRIP6, OXSM, MYH3 and MYH4. These genes predicted COAD patient survival and modulated the tumor microenvironment, drug sensitivity and immune microenvironment. Our study reveals the importance of disulfidptosis-related genes for COAD prognosis and therapy. Immune infiltration and drug susceptibility results provide important clues for finding new personalized treatment options for COAD. These findings may facilitate personalized cancer treatment.

Hu G ，Yao H ，Wei Z ，Li L ，Yu Z ，Li J ，Luo X ，Guo Z ... -  《Scientific Reports》

Construction of disulfidptosis-related lncRNA signature for predicting the prognosis and immune escape in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most frequent types of cancer worldwide. Disulfidptosis has been identified as a new mode of cell death recently. The goal of this study was to explore the possibility of a connection between disulfidptosis and COAD. RNA sequencing data from COAD patients were retrieved from the The Cancer Genome Atlas (TCGA) database for this investigation. R software and various methods were used to identify disulfidptosis-related lncRNAs (DRLs) in COAD, and a prognostic model was created based on 6 DRLs (AP003555.1, AL683813.1, SNHG7, ZEB1-AS1, AC074212.1, RPL37A-DT). The prognostic model demonstrated a good accuracy in predicting the prognosis of COAD patients, according to receiver operating characteristic (ROC) curve and Concordance index (C-index) analyses. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant differences in biological functions and signaling pathways involved in differential genes in risk subgroups, including protein - DNA complex subunit organization, Hippo signaling pathway, Wnt signaling pathway. TIDE analysis was done on risk groupings in this study, and it found that patients in the high-risk group had more immune escape potential and were less probable to react to immunotherapy. Real-time quantitative pcr (qRT-PCR) was used to identify the relatively high expression of 6 DRLs in colon cancer cell lines. In summary, 6 DRLs were identified as possible novel molecular therapy targets for COAD in this investigation. This prognostic model has the potential to be a novel tool for forecasting COAD prognosis in clinical practice, as well as providing new insights on the potential function and mechanism of disulfidptosis in the COAD process.

Chen P ，Yu J ，Luo Q ，Li J ，Wang W ... -  《BMC GASTROENTEROLOGY》

Role of disulfidptosis in colorectal adenocarcinoma: implications for prognosis and immunity.

Recent research has found a new way of cell death: disulfidptosis. Under glucose starvation, abnormal accumulation of disulfide molecules such as Cystine in Solute Carrier Family 7 Member 11 (SLC7A11) overexpression cells induced disulfide stress to trigger cell death. The research on disulfidptosis is still in its early stages, and its role in the occurrence and development of colorectal malignancies is still unclear. In this study, we employed bioinformatics methods to analyze the expression and mutation characteristics of disulfidptosis-related genes (DRGs) in colorectal cancer. Consensus clustering analysis was used to identify molecular subtypes of Colorectal Adenocarcinoma (COAD) associated with disulfidptosis. The biological behaviors between subtypes were analyzed to explore the impact of disulfidptosis on the tumor microenvironment. Constructing and validating a prognostic risk model for COAD using diverse data. The influence of key genes on prognosis was evaluated through SHapley Additive exPlanations (SHAP) analysis, and the predictive capability of the model was assessed using Overall Survival analysis, Area Under Curve and risk curves. The immunological status of different patients and the prediction of drug treatment response were determined through immune cell infiltration, TMB, MSI status, and drug sensitivity analysis. Single-cell analysis was employed to explore the expression of genes at the cellular level, and finally validated the expression of key genes in clinical samples. By integrating the public data from two platforms, we identified 2 colorectal cancer subtypes related to DRGs. Ultimately, we established a prognosis risk model for COAD using 7 genes (FABA4+GIPC2+EGR3+HOXC6+CCL11+CXCL10+ITLN1). SHAP analysis can further explained the positive or negative impact of gene expression on prognosis. By dividing patients into high-risk and low-risk groups, we found that patients in the high-risk group had poorer prognosis, higher TMB, and a higher proportion of MSI-H and MSI-L statuses. We also predicted that drugs such as 5-Fluorouracil, Oxaliplatin, Gefitinib, and Sorafenib would be more effective in low-risk patients, while drugs like Luminesib and Staurosporine would be more effective in high-risk patients. Single-cell analysis revealed that these 7 genes not only differ at the level of immune cells but also in epithelial cells, fibroblasts, and myofibroblasts, among other cell types. Finally, the expression of these key genes was verified in clinical samples, with consistent results. Our research findings provide evidence for the role of disulfidptosis in COAD and offer new insights for personalized and precise treatment of COAD.

Yang R ，Lai C ，Huang L ，Li F ，Peng W ，Wu M ，Xin J ，Lu Y ，Ouyang M ，Bai Y ，Lei H ，He S ，Lin Y ... -  《Frontiers in Immunology》

Developing a prognosis and chemotherapy evaluating model for colon adenocarcinoma based on mitotic catastrophe-related genes.

Liu Y ，Zhao Y ，Zhang S ，Rong S ，He S ，Hua L ，Wang X ，Chen H ... -  《Scientific Reports》

Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer.

Dong X ，Liao P ，Liu X ，Yang Z ，Wang Y ，Zhong W ，Wang B ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》