Purpose

Stem cells-like properties in cancer cells may confer cancer development and therapy resistance. With the advancement of multi-omics technology, the multi-omics-based exploration of cancer stemness has attracted certain interests. However, subtyping of cancer based on the combination of different types of stem cell signatures remains scarce.

Methods

In this study, 10,323 cancer specimens from 33 TCGA cancer types were clustered based on the enrichment scores of six stemness gene sets, representing two types of stem cell backgrounds: embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs).

Results

We identified four subtypes of pan-cancer, termed StC1, StC2, StC3 and StC4, which displayed distinct molecular and clinical features, including stemness, genome integrity, intratumor heterogeneity, methylation levels, tumor microenvironment, tumor progression, chemotherapy and immunotherapy responses, and survival prognosis. This subtyping method for pan-cancer is reproducible at the protein level.

Conclusion

Our findings indicate that the ESC signature is an adverse prognostic factor, while the HSC signature and ratio of HSC/ESC signatures are positive prognostic factors in cancer. The ESC and HSC signatures-based subtyping of cancer may provide insights into cancer biology and clinical implications of cancer.