Abstract 5350: Establishment and validation of a prognostic signature based on thirteen hub genes in colorectal cancer

Background: The survival rate for late-stage colorectal cancer (CRC) is extremely low (4%-12%). The prognosis assessment for CRC pose numerous challenges. Recently, the role of the immune microenvironment in CRC progression has increasingly garnered attention, with immune cell infiltration and molecular expression closely related to patient prognosis. Therefore, this study aims to deeply analyze the molecular mechanisms underlying CRC and identify novel immune-related biomarkers for prognosis evaluation. Methods: High-throughput sequencing technology was utilized to compare and analyze the differential gene expression between CRC tumor tissues and normal tissues, as well as between patients with long and short survival durations. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (Lasso) regression analysis were combined to screen hub genes closely related to CRC prognosis. A prognostic signature based on these hub genes was constructed to predict the prognosis of CRC patients. RNA sequencing (RNA-Seq) data from five paired CRC patients were collected to validate the expression patterns of the hub genes in CRC samples and their relationship with the immune microenvironment. Results: We successfully identified 13 hub genes (HOXC6, IGF2BP3, SGCG, HTR2C, ADCY5, SHC2, SUCLG2, PDHB, TSLP, CCR9, TNFRSF19, TGFB2, and LEP) that compose the prognostic signature. In the Cancer Genome Atlas (TCGA) dataset, this signature accurately classified patients into high- and low-risk groups with high precision (p < 0.001). Similar results were obtained in the Gene Expression Omnibus (GEO) dataset (p < 0.001 and p = 0.036). The study also found that when patients were stratified into high-risk and low-risk groups using the prognostic signature, there were significant differences in the immune environment between the two groups, including the infiltration degree of immune cells (p < 0.001) and the expression levels of immune molecules(p < 0.01). Additionally, when validated using RNA-Seq data from five paired CRC patients, the expression patterns of these hub genes in the five CRC samples were consistent with those observed in the TCGA analysis, further confirming the important roles of the 13 hub genes in CRC patients and their association with the immune microenvironment. Conclusion: In summary, this research has developed a novel signature that can predict both the survival outcomes and the immune infiltration status of CRC patients. The clinical application of this signature has the potential to enhance survival rates and individualize therapy approaches for CRC based on their risk score. Citation Format: Hui Zhang, Yu Lang, Zhaoqi Tang, Jialin Lin, Lu Yang, Jiapeng Kang, Changshun Yang, Qin Lin, Qiyuan Li, Feng Ye, Weiwei Tang. Establishment and validation of a prognostic signature based on thirteen hub genes in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5350.