A telomere-associated molecular landscape reveals immunological, microbial, and therapeutic heterogeneity in colorectal cancer

作者：Yinmeng Zhang, Jiawei Fan, Jiahui Zhao, He Zhu, Yan Xia, Hong Xu · 发表于：Frontiers in Molecular Biosciences · 年份：2025 · DOI：10.3389/fmolb.2025.1615533 · 被引用次数：5 · 研究领域：Telomeres, Telomerase, and Senescence、Cancer Immunotherapy and Biomarkers、Single-cell and spatial transcriptomics

Background: Colorectal cancer (CRC) ranks among the most prevalent malignancies of the gastrointestinal tract and remains a leading cause of cancer-related mortality worldwide. Although telomere biology has been increasingly implicated in immune modulation and tumor progression, its clinical significance in CRC remains poorly understood. Methods: We developed a telomere score, termed TELscore, by integrating transcriptomic and intratumoral microbiome profiles from publicly available colorectal cancer (CRC) cohorts. To comprehensively characterize TELscore subgroups, we performed pathway enrichment analysis, tumor immune microenvironment (TIME) profiling, and microbiome niche assessment. Whole-slide histopathological images (WSIs) and immunohistochemical (IHC) staining were utilized to visualize immune features, including tertiary lymphoid structures (TLSs), across subgroups. Patients were stratified into high and low TELscore categories, and the predictive robustness was validated across multiple independent training and validation cohorts. Chemotherapeutic drug sensitivity was evaluated using pharmacogenomic data from the Genomics of Drug Sensitivity in Cancer (GDSC) database. Furthermore, the predictive capacity of TELscore for immunotherapy response was independently assessed in an external cohort. Finally, single-cell RNA sequencing (scRNA-seq) analysis was conducted to further dissect the cellular landscape and immunological heterogeneity within the TME. Results: TELscor...