Acquisition and validation of four pain subtypes of colon adenocarcinoma and prognostic analysis.

Background: Colon adenocarcinoma (COAD) is the most common type of colorectal cancer. Pain is a multidimensional unpleasant experience involving various molecular and cellular pathways. Nevertheless, the exploration of pain-related genes related to colon adenocarcinoma remains unclear yet. Methods: In this study, the pathways enriched with pain-related genes were analyzed using Metascape. Then, we identified pain subtypes and classical subtypes and explored the link between them. Next, marker genes for different pain subtypes were identified, and their enrichment pathways were explored. These marker genes were then used to validate the pain subtypes. Subsequently, we performed an investigation of survival differences between pain subtypes by selecting specific top pathways in each subtype, calculating top pathway scores and pathway differences using heatmap and Kruskal test. Finally, we predicted the response of different pain subtypes to immunotherapy. Results: A total of 146 pain-related genes were included in this study and we finally identified 4 pain subtypes and 4 stable subtypes. The marker genes for subtypes were validated by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, revealing a worse prognosis for CS1. The genes of CS1, CS2, CS3 and CS4 markers were primarily enriched in the pathways of Focal adhesion, Human T cell leukemia virus1 infection, Metabolic pathway, and Pertussis, respectively. CS1 and CS4 were found to be more immunogenic. Moreover, CS1 was more sensitive to treatment with CTLA4 inhibitors, while CS4 was sensitive to treatment with PD-1 inhibitors. Conclusions: Our study's identification of four pain subtypes of COAD provides new insights for personalized therapy for patients with COAD.