Comprehensive analysis of complement-associated molecular features in hepatocellular carcinoma

The complement cascade plays a complementing role in human immunity. However, the potential roles of complement system in impacting molecular and clinical features of hepatocellular carcinoma (HCC) remain unclear. In this study, eleven public datasets are analyzed to compare the complement status between normal and cancerous samples based on 18 classical complement-associated genes. The complement scores are constructed to quantify complement signatures of individual tumors. HCC patients in the The Cancer Genome Atlas (TCGA) cohort are focused to perform systematical analyses between complement status and immune infiltration, miRNA expression, DNA methylation, clinicopathological features, and drug response. The results show that the complement scores in normal tissues are dramatically higher than those of tumor tissues. Tumor samples in the TCGA cohort are classified into complement score-low and score-high groups. Pathway analysis reveals that tumor-promoting pathways are typically inhibited in complement score-high group. This study also shows that tumor-killing immune cells, such as CD8(+) T cells and natural killer cells are abundant and tumor-suppressing miRNAs are upregulated in complement score-high samples. In addition, we identify that complement scores are negatively correlated with certain clinical features, including pathological grade, clinical-stage, and portal vein invasion. Moreover, various molecular features together with complement scores are found to be correlated with response to anti-cancer drugs. This study provides a comprehensive and multidimensional analysis conducive to understanding the role of complement in cancer.

Automated summary

The complement cascade plays a complementary role in human immunity, but its potential effects on the molecular and clinical features of hepatocellular carcinoma (HCC) have been unclear. This study analyzed eleven public datasets to compare complement status between normal and cancerous samples, and found that complement scores in normal tissues were significantly higher than those in tumor tissues. The study also revealed correlations between complement status and immune infiltration, miRNA expression, DNA methylation, clinicopathological features, and drug response in HCC patients. These findings provide a comprehensive analysis of the role of complement in cancer.