Oncogene-Induced Senescence Transcriptomes Signify Premalignant Colorectal Adenomas

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Oncogene-induced senescence (OIS) is a critical tumor-suppressive mechanism halting premalignant cell proliferation.
• Understanding OIS's role in colorectal tumorigenesis is vital for cancer prevention strategies.
• This study investigates OIS transcriptomic landscapes in colorectal adenomas and their progression to cancer.

Purpose of the Study:

• To analyze OIS and senescence-associated secretory phenotype (SASP) signatures in colorectal adenomas versus adenocarcinomas.
• To identify key senescence-related genes and their expression patterns during colorectal tumor progression.
• To determine if OIS resolution contributes to adenoma-to-carcinoma transition.

Main Methods:

• Utilized a public gene expression dataset (GSE117606) of 66 paired adenoma-adenocarcinoma samples.
• Employed single-sample gene set enrichment analysis (ssGSEA) for OIS and SASP signature assessment.
• Conducted differential gene expression analysis for senescence regulators and SASP factors.

Main Results:

• OIS and SASP signatures were significantly enriched in adenomas compared to adenocarcinomas (p < 0.05).
• 65% of patients showed higher OIS scores in adenomas; SASP enrichment declined in 59-61% of cases.
• Key senescence regulators (e.g., CDKN1A, CDKN2B) and SASP factors were downregulated in adenocarcinomas, indicating reduced senescence signaling.

Conclusions:

• OIS phenotypes are predominant in colorectal adenomas, acting as a potential tumor-suppressive barrier.
• The resolution of OIS and SASP signaling correlates with adenoma-to-carcinoma progression.
• These findings highlight OIS's role in early colorectal cancer development and its potential as a therapeutic target.