Prognostic costimulatory molecule-related signature risk model correlates with immunotherapy response in colon cancer

Abstract

Costimulatory molecules can promote the activation and proliferation of T cells and play an essential role in immunotherapy. However, their role in the prognosis of colon adenocarcinoma remains elusive. In this study, the expression data of costimulatory molecules and clinicopathological information of 429 patients with colon adenocarcinoma were obtained from The Cancer Genome Atlas database. The patients were divided into training and verification cohorts. Correlation, Cox regression, and Lasso regression analyses were performed to identify costimulatory molecules related to prognosis. After mentioning the construction of the risk mode, a nomogram integrating the clinical characteristics and risk scores of patients was constructed to predict prognosis. Eventually, three prognostic costimulatory molecules were identified and used for constructing a risk model. High expression of these three molecules indicated a poor prognosis. The predictive accuracy of the risk model was verified in the GSE17536 dataset. Subsequently, multivariate regression analysis showed that the signature based on the three costimulatory molecules was an independent risk factor in the training cohort (HR = 2.12; 95% CI = 1.26, 3.56). Based on the risk model and clinicopathological data, the AUC values for predicting the 1-, 3-, and 5-year survival probability of patients with colon adenocarcinoma were 0.77, 0.77, and 0.71, respectively. To the best of our knowledge, this study is the first to report a risk signature constructed based on the costimulatory molecules TNFRSF10c, TNFRSF13c, and TNFRSF11a. This risk signature can serve as a prognostic biomarker for colon adenocarcinoma and is related to the immunotherapeutic response of patients.

Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer

“…Comparison of our gene signature with other COAD prognostic models. In order to assess the superiority of our gene signature over other COAD prognostic models, we conducted a comparison of 10 models across the entire TCGA cohort [24][25][26][27][28][29][30][31][32][33] . The 1-year AUC values for all 10 prognostic models were observed, and our findings indicated that our model incorporating the 5 gene signatures had significantly superior predictive power compared to the other 10 prognostic models (Supplementary Fig.…”

Exploration of the prognostic effect of costimulatory genes in bladder cancer

“…The immune response to bladder cancer is highly influenced by the interaction between tumor cells and immune cells in the tumor microenvironment. 2,3 As crucial components of the immune system, costimulatory molecules are attracting increasing attention in cancer research. 4 Costimulatory molecules are a group of proteins expressed on the immune cell surface, which regulate the immune response by modulating T-cell activation.…”

“…The development and progression of bladder cancer are greatly influenced by the immune system. The immune response to bladder cancer is highly influenced by the interaction between tumor cells and immune cells in the tumor microenvironment 2,3 . As crucial components of the immune system, costimulatory molecules are attracting increasing attention in cancer research 4 …”

CD81 and CD82 expressing tumor-infiltrating lymphocytes in the NSCLC tumor microenvironment play a crucial role in T-cell activation and cytokine production

“…Ongoing research on co-stimulation has made significant progress, leading to the discovery of numerous novel molecules through systematic examinations ( 18 ). However, the target co-stimulatory molecule should be selected with careful consideration as the function of co-stimulation varies among T-cell subsets.…”