Profiling of Tumor Microenvironment Components Identifies Five Stroma-Related Genes with Prognostic Implications in Colorectal Cancer

Colorectal Cancer

Cancer Biother Radiopharm. 2020 Oct 21. doi: 10.1089/cbr.2020.4118. Online ahead of print.


Background: Tumor microenvironment (TME) significantly affects colorectal cancer (CRC) progression and therapeutic efficacy, particularly the infiltrating stromal components. This study aimed to profile the TME composition of tumor tissue and identify TME-related, especially stroma-related genes having prognosis value in CRC patients. Materials and Methods: We used ESTIMATE algorithm to assess stromal/immune component and divided 524 CRC cases of public dataset into high- and low-score groups. We analyzed effect of the score on prognosis and extracted the differential expression genes (DEGs) between groups, which were stromal- and/or immune-related genes, and performed prognostic investigation of the DEGs. Results: Higher stromal score was correlated with poor survival, whereas immune score was the opposite. By comparing global gene expression of cases with high vs. low stromal/immune scores, we extracted 474 stroma-related genes, 76 immune-related genes, and 498 intersection genes, which were explored by function enrichment and survival analysis. We identified the expression of five stroma-related genes (including ITGA7, PTPN14, SCG2, TNS1, and GRP) significantly associated with poorer survival, which were validated in the other two independent CRC cohorts. Conclusion: These results presented a comprehensive understanding of TME components and identified five stroma-related genes that predict poor outcomes in CRC patients.