Integrative Analysis of Complement System to Prognosis and Immune Infiltrating in Colon Cancer and Gastric Cancer

Abstract

Background: The complement system acts as an integral part of the innate immune response, which acts primarily to remove pathogens and injured cells. Emerging evidence has shown the activation of the immune regulatory function of complements in the tumor microenvironment (TME). We revealed the expression levels of various complements in human cancers and their role in tumor prognosis and immune infiltration. Methods: The differential expression of complements was explored via the Tumor Immune Estimation Resource (TIMER) site and the Oncomine database. To investigate whether these differentially expressed complements have correlation with the prognosis of gastric cancer (GC) and colon cancer, their impact on survival was assessed using the PrognoScan database and Kaplan-Meier plotter. The correlations between complements and tumor immune-infiltrating levels and immune gene markers were statistically explored in TIMER based on Spearman’s correlation coefficients and p-values. Results: In two colon cancer cohorts, an increased expression level of DAF (CD55) has statistically significant correlation with poor disease-free survival (DFS). High C3, CR4, and C5aR1 expression levels were significantly related with poor prognosis in GC patients. In addition, C3, CR4, and C5aR1 expression was positively related to the tumor purity and infiltration levels of multiple immune cells in stomach adenocarcinoma (STAD). Moreover, the expression levels of C3, CR4, and C5aR1 were also strongly correlated with various immune marker sets, such as those of tumor-associated macrophages (TAMs), M1 and M2 macrophages, T cell exhaustion, Tregs, and DCs, in STAD. Additionally, CD55 has positive correlation with few immune cell infiltration levels in colon adenocarcinoma (COAD), but its correlation with immune marker sets was not statistically significant. Conclusion: These findings confirm the relationship between various complements and tumor prognosis and immune infiltration in colon cancer and GC. CD55 may serve as an indicator on the survival prognosis of patients with colon cancer. Furthermore, as biomarkers for poor prognosis in GC, complements C3, CR4, and C5aR1 may provide potential biological targets for GC immunotherapy.