Uncovering Stage-Specific Biomarkers in Colorectal Cancer: RNA-Seq Analysis of Adenoma and Carcinoma Progression
Colorectal cancer (CRC) progresses through distinct molecular mechanisms, tumor stage playing a pivotal role in prognosis and treatment outcomes. Despite advances in CRC treatment, the lack of stage-specific biomarkers limits the potential for reliable diagnostic and treatment strategies. This study aims to identify stage-specific gene expression profiles and the molecular mechanisms through comparative transcriptomic analysis of adenoma (n = 10), carcinoma in situ (n = 8) and adenocarcinoma (n = 11) samples. Utilizing RNA-seq from FFPE samples processed with absGSEA, we identified significant cellular pathways influenced from each CRC stage. In adenocarcinoma, pathways related to transcriptional co-regulatory mechanisms and protein kinase functional activity, critical for tumor growth and metastasis, were significantly enriched compared to adenoma. While apoptotic processes and Wnt signaling pathways were prominent in carcinoma in situ compared to adenoma samples. Extracellular matrix organization pathway was significantly enriched between adenocarcinoma and carcinoma in situ. Transcriptomics data and bioinformatics analysis revealed that in adenocarcinoma cohorts, genes such as COL1A2, CEBPZ, MED10, and PAWR were overexpressed, highlighting their potential roles in advanced disease progression. Conversely, in adenoma samples, the overexpression of genes such as ARRB1, CTBP1, and CTBP2 underscores their involvement in early tumorigenesis. COL1A2 and CEBPZ were implicated in extracellular matrix remodeling and transcriptional regulation respectively, while and ARRB1 were associated with early tumorigenesis. These findings highlight the complexity of gene regulation in CRC and provide a foundation for developing stage-specific diagnostic and prognostic biomarkers, and to ultimately improve therapeutic strategies. Overall design: 10 adenoma samples 11 adenocarcinoma samples 8 Carcinoma In Situ samples Abbreviations: (AD: Adenoma patients, CA: Carcinoma patients, CIS: Carcinoma In Situ)