Abstract 3546: Putting genes in context by linking gene signatures to established cancer hallmarks

Abstract

Abstract The concept of the "Hallmarks of Cancer" provides a valuable framework for understanding fundamental organizing principles common to various types of cancers. However, the absence of a consensus gene set for cancer hallmarks poses data comparison and integration challenges, resulting in diverse biological interpretations across studies. Here, we first established a consensus cancer hallmark-gene set by merging data from available mapping resources. We searched the scientific literature for relevant publications from which a list of hallmark genes could be reconstructed. By consolidating data from seven publications, we identified 6,763 candidate cancer hallmark genes associated with ten cancer hallmarks. Of these, 1574 genes were part of at least two resources, forming a "core" hallmark gene set. Then, we compared the enrichment of cancer hallmarks by analyzing the prognostic genes associated with overall survival across twelve solid tumor types. Notably, the hallmark "tissue invasion and metastasis" was most prominent in the stomach (p=1.2E-11), pancreatic (p=1.5E-09), bladder (p=1.8E-08), and ovarian cancers (p=0.0002), aligning with their heightened potential to spread. "Sustained angiogenesis" predominated in lung squamous carcinomas (p=4.5E-08), while "genome instability" showed strong enrichment in lung adenocarcinomas (p=1.3E-09), liver (p=1.4E-10), pancreatic (p=1E-5) and kidney cancers (p=0.0025). Compelling evidence links lifestyle choices like alcohol consumption and smoking to genomic instability across tumors, suggesting a potential common underlying mechanism of tumorigenesis. Pancreatic cancers displayed the highest enrichment of hallmarks (8 out of 10), emphasizing the disease's complexity, while in melanomas, liver, and kidney cancer, a single hallmark (,,genomic instability”) was enriched among the prognostic markers of survival. These findings underscore the utility of the hallmark concept as an effective organizational tool, particularly when establishing a clear connection between genes and biological functions. Finally, we integrated the data into a publicly accessible and user-friendly online tool (available at www.cancerhallmarks.com) that allows users to identify the most relevant cancer-associated "candidate hallmark genes" in their datasets. In summary, we have established a consensus list of genes associated with cancer hallmarks. The analysis of survival-associated genes revealed a unique pattern of hallmark enrichment for each tumor type. Citation Format: Otília Menyhart, William Kothalawala, Balázs Győrffy. Putting genes in context by linking gene signatures to established cancer hallmarks [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3546.