Solid pancancer analysis reveals immune and hematopoietic stem cell and DNA damage repair signatures to distinguish different cancer subtypes

Abstract

Purpose

Immunity, stemness, and DNA damage repair (DDR) are crucial for cancer development and therapy resistance. With advancements in multiomics technology, the exploration of cancers related to immunity, stemness, and the DDR has triggered interest, but the combination of these levels for analyzing multiple cancers remains insufficient.

Methods

In this study, 9906 solid tumor samples from 31 TCGA cancer types were clustered on the basis of the enrichment levels of 13 gene sets associated with stemness, immunity, and DDR. Moreover, a soft ensemble model was constructed on the basis of the enrichment levels of these 13 gene sets to predict cancer subtypes via other omics data.

Results

We identified four pancancer subtypes, termed C1, C2, C3, and C4, which presented distinct molecular and clinical features, including the immune microenvironment, stemness, genome instability, intratumor heterogeneity, methylation levels, tumor progression, sensitivity to chemotherapy and immunotherapy, and survival prognosis. The soft ensemble model validated this subtyping method in two breast cancer datasets (gene expression level), a pancancer proteomic dataset (protein expression level), and a pancancer cell line dataset (cell line gene expression level).

Conclusion

Our findings indicate that immune, stemness, and DDR signature-based subtyping offers new perspectives on cancer biology and holds promise for improving the clinical management of cancers.