Crucial role of telomere maintenance-related genes in survival prediction and subtype identification in colorectal cancer

Abstract Telomere maintenance genes are closely related to colorectal cancer (CRC) development and progression. However, the potential influence of telomere maintenance-related genes (TMRGs) on the prognosis of CRC and their clinical relevance remains insufficiently explored. Utilizing mRNA expression data from the Cancer Genome Atlas (TCGA), we developed a risk model with three telomere maintenance-related biomarkers ( PDE1B , TFAP2B , and HSPA1A ). Then, the risk score, pathologic N, pathologic M, and age were identified as independent prognostic factor. Through the integration of model risk score with clinical information, we drew a nomogram to predict the survival outcomes of patients with CRC. We further divided the patients into two risk subgroups. Concomitantly, an in-depth analysis of the immuno-infiltration, functional variation and drug sensitivity analysis were performed in two risk subgroups. Ultimately, we experimentally validated the impact of PDE1B in CRC cell lines. The qPCR results showed expression level of PDE1B in CRC cells were lower than the control cells, which was consistent with gene expression analysis by the UALCAN database. Overexpression of PDE1B in CRC cells significantly inhibited proliferation, metastasis, while promoted apoptosis in vitro . In conculsion, three telomere maintenance-related biomarkers and effective prognostic model was developed to provide a basis for exploring the prediction of prognosis of CRC. Different subtypes can be utilized to further subdivide the CRC patient for a more precise treatment plan. Our study suggests that PDE1B may serve as both a biomarker and a therapeutic target for CRC.