A gene set enrichment analysis for cancer hallmarks

Ot&#237;lia Menyhart; William Jayasekara Kothalawala; Bal&#225;zs Gy&#337;rffy

doi:10.1016/j.jpha.2024.101065

Volume 15 Issue 5

Jun. 2025

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Otília Menyhart, William Jayasekara Kothalawala, Balázs Győrffy. A gene set enrichment analysis for cancer hallmarks[J]. Journal of Pharmaceutical Analysis, 2025, 15(5): 101065. doi: 10.1016/j.jpha.2024.101065

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Otília Menyhart, William Jayasekara Kothalawala, Balázs Győrffy. A gene set enrichment analysis for cancer hallmarks[J]. Journal of Pharmaceutical Analysis, 2025, 15(5): 101065. doi: 10.1016/j.jpha.2024.101065

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A gene set enrichment analysis for cancer hallmarks

doi: 10.1016/j.jpha.2024.101065

a. Cancer Biomarker Research Group, Institute of Molecular Life Sciences, Hungarian Research Network, Budapest, 1117, Hungary;
b. National Laboratory for Drug Research and Development, Budapest, 1117, Hungary;
c. Department of Bioinformatics, Semmelweis University, Budapest, 1094, Hungary;
d. Department of Biophysics, Medical School, University of Pecs, Pecs, 7624, Hungary

Funds:

This project was supported by the National Research, Development, and Innovation Office, Hungary (PharmaLab, Grant No.: RRF-2.3.1-21-2022-00015). Otília Menyhart was supported by the Janos Bolyai Scholarship of the Hungarian Academy of Sciences and the Hungarian Scientific Research Fund (Grant No.: OTKA FK147194).

Received Date: Jan. 03, 2024
Accepted Date: Aug. 01, 2024
Rev Recd Date: Jun. 18, 2024
Publish Date: Aug. 03, 2024

Abstract

Abstract

The “hallmarks of cancer” concept provides a valuable framework for understanding fundamental organizing principles common to various cancers. However, without a consensus gene set for cancer hallmarks, data comparison and integration result in diverse biological interpretations across studies. Therefore, we aimed to form a consensus cancer hallmark gene set by merging data from available mapping resources and establishing a framework for mining these gene sets. By consolidating data from seven projects, 6763 genes associated with 10 cancer hallmarks were identified. A cancer hallmarks enrichment analysis was performed for prognostic genes associated with overall survival across 12 types of solid tumors. “Tissue invasion and metastasis” was most prominent in cancers of the stomach (P = 2.2 × 10^-11), pancreas (P = 4.2 × 10^-9), bladder (P = 3.3 × 10^-8), and ovaries (P = 0.0007), aligning with their heightened potential to spread. “Sustained angiogenesis” was most prominent in squamous cell carcinomas of the lung (P = 2.5 × 10^-7), while “genome instability” showed strong enrichment in lung adenocarcinomas (LUADs) (P = 1.5 × 10^-8) and cancers of the liver (P = 5.5 × 10^-10), pancreas (P = 2.1 × 10^-5), and kidney (P = 0.018). Pancreatic cancers displayed the highest enrichment of hallmarks, emphasizing the disease's complexity, while in melanomas and cancers of the liver, prostate, and kidney, a single hallmark was enriched among the prognostic markers of survival. Additionally, an online tool (www.cancerhallmarks.com) that allows the identification of cancer-associated hallmarks from new gene sets was established. In summary, our aim of establishing a consensus list of cancer hallmark genes was achieved. Furthermore, the analysis of survival-associated genes revealed a unique pattern of hallmark enrichment with potential pharmacological implications in different tumor types.
- Cancer hallmarks,
- Candidate hallmark genes,
- Overrepresentation analysis,
- Pharmacology,
- Drug development,
- New drug targets,
- Pan-cancer

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References(65)

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