Identification of mutation associated-immunotype and prediction of survival in patients with hepatocellular carcinoma.

BACKGROUND

Stratification of tumors is necessary to achieve better clinical outcomes. Hepatocellular carcinoma (HCC) is commonly associated with mutation of the gene and heterogeneity in immune cell content. However, mutation-associated immunotype of HCC has not been reported yet. This study aimed to identify the mutation-associated immunotype in HCC.

METHODS

The mutation annotation format (MAF) document, mRNA expression data, and clinical data of HCC patients were downloaded from the publicly available The Cancer Genome Atlas (TCGA) data portal. Data from 332 HCC patients were analyzed in this study. Infiltrating immune cells were evaluated by the well-known CIBERSORT method. Additional mutation data of HCC patients were downloaded from the Catalogue of Somatic Mutations in Cancer (COSMIC) database.

RESULTS

The gene harbored the highest frequency of mutations in HCC patients. Consequently, five lethal features, including mutations, were screened by least absolute shrinkage and selector operation (LASSO)-COX regression, according to mutations and 22 infiltrating immune cells. Two distinct subgroups of HCC were identified, namely, immunotypes A and B. Furthermore, the expression levels of co-inhibitory immune checkpoints were significantly upregulated, and the gene ontology (GO) terms or pathways to boost immune responses were found to be inhibited in the immunotype B subgroup compared to that in the immunotype A subgroup. Finally, we proved immunotype to be an independent adverse prognostic factor that contributed to improvement in the predictive accuracy of the immunotype-based model and helped in avoiding excessive medical treatment.

CONCLUSIONS

Two distinct immunotypes of HCC, in terms of prognosis, phenotype, and function, were identified and the traditional understanding of intratumoralCD8 T cells was subverted. Moreover, the identified immunotypes contributed to improving the predictive accuracy of the immunotype-based model and helped in avoiding excessive medical treatment in some HCC patients.