RESUMEN
BACKGROUND: Increasing evidence has shown that cytolytic activity (CYT) is a new immunotherapy biomarker that characterises the antitumour immune activity of cytotoxic T cells and macrophages. In this study, we established a prognostic model associated with CYT. METHODS: A prognostic model based on CYT-related genes was developed. Furthermore, aberrant expression of genes of the model in colon cancer (CC) was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next, the correlation between the model and T-cell infiltration in the CC microenvironment was analysed. The Tumour Immune Dysfunction and Exclusion (TIDE) algorithm and subclass mapping were used to predict clinical responses to immune checkpoint inhibitors. RESULTS: In total, 280 of the 1418 genes were differentially expressed based on CYT. A prognostic model (including HOXC8 and MS4A2) was developed based on CYT-related genes. The model was validated using the testing set, the whole set and a Gene Expression Omnibus (GEO) cohort (GSE41258). Gene set enrichment analysis (GSEA) and other analyses showed that the levels of immune infiltration and antitumour immune activation in low-risk-score tumours were greater than those in high-risk-score tumours. CC patients with a low-risk-score showed more promise in the response to anti-immune checkpoint therapy. CONCLUSIONS: Overall, our model may precisely predict the overall survival of CC and reflect the strength of antitumour immune activity in the CC microenvironment. Furthermore, the model may be a predictive factor for the response to immunotherapy.
RESUMEN
Currently, colorectal cancer (CRC) predictions are based on an early diagnosis and the tumor-node-metastasis (TNM) stage, but the outcomes of patients with the same cancer type are difficult to predict. Novel molecular tests for the early diagnosis and stratification of CRC patients must be devised. After our initial bioinformatics screen, we examined zinc finger and BTB domain-containing 7C (ZBTB7C). To date, few studies have investigated ZBTB7C in CRC, necessitating further analyses of its expression and regulatory mechanism in CRC. ZBTB7C mRNA and protein expression was detected in CRC and corresponding non-CRC tissues. We evaluated the relationship between clinical prognosis and ZBTB7C protein levels using Cox regression analysis and Kaplan-Meier curves. A receiver operating characteristic (ROC) curve was generated to verify the diagnostic performance of ZBTB7C levels in CRC. Several bioinformatics techniques were applied to analyze the potential molecular mechanism of ZBTB7C. Low mRNA and protein levels of ZBTB7C were detected in tumor tissues from CRC patients. The survival curve predicted a poor prognosis for CRC patients exhibiting low ZBTB7C expression (P=0.001). According to the univariate Cox regression analysis, older age, a high TNM stage and low ZBTB7C expression were responsible for poor outcomes in CRC patients. The multivariate analysis further revealed ZBTB7C as an independent prognostic factor for CRC (P=0.015). The area under the curve of ZBTB7C expression for CRC diagnosis was 0.970 (95% confidence interval, 0.9447-0.9946; P < 0.0001). According to in silico analyses, genes coexpressed with ZBTB7C are associated mainly with the Ras and Wnt signaling pathways. Overall, ZBTB7C is downregulated in CRC and represents an early diagnostic marker and independent prognostic factor for CRC. ZBTB7C may be functionally mediated by different pathways or targeting miRNAs.