APMAdvances in Precision Medicine2424-85922424-9106WHIOCE PUBLISHING PTE. LTD.10.18063/APM.v11i2.1424ArticleSystematic Downregulation of T-Cell Pathways Distinguishes Recurrent from Non-Recurrent Colorectal Cancerhttps://artdesignp.com/journal/APM/11/2/10.18063/APM.v11i2.1424BiPengfei,ZhangYuhan,QiaoTianyu,JinYinghu,MaTianyi20261122026-02-26This study compared the transcriptomic profiles of recurrent and non-recurrent colorectal cancer (CRC) patients in the GSE39582 cohort and identified immune-related alterations—particularly those involving T-cell functional pathways—as the dominant molecular features associated with recurrence. Differential expression analysis revealed extensive downregulation of immune-related genes in recurrent patients, while heatmap clustering demonstrated a consistent reduction in transcripts involved in T-cell activation, proliferation, and effector functions. Gene Ontology (GO) enrichment showed that downregulated genes were predominantly enriched in key immune processes such as “T cell activation,” “lymphocyte proliferation,” and “leukocyte cell–cell adhesion.” Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis further indicated suppression of multiple essential immune pathways, including Th1/Th2/Th17 differentiation, chemokine signaling, antigen processing and presentation, and B/T-cell receptor signaling. Immune checkpoint analysis showed reduced expression of LAG3 and CTLA4 in the recurrent group, whereas PDCD1, PDCD1LG2, and SIGLEC15 exhibited no significant differences. Collectively, these findings reveal a transcriptional signature characterized by T-cell immune suppression and an immune-cold phenotype in recurrent CRC, suggesting that impaired T-cell activation may be a key molecular driver of recurrence.Colorectal cancer, Recurrence, T-cell immunity, Transcriptomics, Immune-cold microenvironment

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