37P - A consensus gene set facilitates enrichment analysis of cancer hallmarks

Background

The "Hallmarks of Cancer" framework is foundational for understanding common organizational principles underlying diverse cancer types. However, the absence of a consensus gene set for cancer hallmarks leads to varied biological interpretations across studies. In this work, we established a unified cancer hallmark gene set by merging data from existing mapping resources and devising a framework for gene set mining.

Methods

We searched the NCBI PubMed database for publications from which a list of cancer hallmark genes could be extracted or reconstructed. Then, we performed a cancer hallmarks enrichment analysis on a list of differentially expressed genes between normal and tumor tissues across eleven solid tumor types.

Results

Consolidating hallmark genes from seven projects, we identified 6,763 genes associated with ten cancer hallmarks. We discovered a hallmark enrichment “fingerprint” specific to each tumor type. Notably, kidney cancers displayed the most extensive hallmark enrichment, underscoring the complexity of the disease. Hallmarks linked to immune function, such as “Evading immune destruction” and “Tumor promoting inflammation” were prominently enriched in kidney and CNS cancers (p<0.0001). “Tissue invasion and metastasis” was the single most prominent hallmark in skin and pancreatic cancers (p<0.0001), known to metastasize early. "Reprogramming energy metabolism" emerged as the hallmark particularly enriched in breast, ovarian, and uterine cancers (p<0.0001), suggesting the feasibility of metabolic approaches to target these cancers. The hallmark “Genome instability” was significantly enriched in cancers frequently associated with lifestyle choices, including colon, oesophageal, and liver cancers (p<0.05), and in cervical cancers, known to be linked to HPV infection (p<0.0001). To facilitate the analysis of cancer hallmarks, we developed an online tool (www.cancerhallmarks.com) to identify cancer-associated hallmarks from novel gene sets.

Conclusions

We established a consensus list of cancer hallmark genes and delineated unique patterns of hallmark enrichment across diverse tumors. Our findings hold potential pharmacological implications and enhance the utility of the hallmark concept as an effective organizational tool.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This project was supported by the National Research, Development, and Innovation Office (PharmaLab, RRF-2.3.1-21-2022-00015) in Hungary. O.M. was supported by the Janos Bolyai Scholarship of the Hungarian Academy of Sciences and the Hungarian Scientific Research Fund (OTKA FK147194). The support of ELIXIR Hungary (www.bioinformatics.hu) is acknowledged.

Disclosure

All authors have declared no conflicts of interest.