Profiling neoadjuvant therapy response in rectal cancer using meta-analysis of publicly available transcriptomic RNA-seq datasets.

Abstract

Neoadjuvant chemoradiotherapy followed by total mesorectal excision is standard for locally advanced rectal cancer, but response varies and current markers are insufficient. This study integrates public bulk RNA-seq data to identify predictive features of response. TRIM54 and PABPC4 were upregulated in the responder group, while ADSS1 and MGAT1 were upregulated in the non-responder group. ARMC2 was identified as a predictive biomarker upregulated in pathological complete response. Responder group showed enrichment of NK cells and CD4+ lymphocytes, while immune precursors were linked to poor outcome. Transcription factor analysis revealed SP1 and NFKB activations in the non-responder group and TCF15 in the responder group. SMAD3 and RDXANK were associated with complete regression, while MYC was dominant in incomplete regression. These findings provide insight into mechanisms underlying therapy response. To our knowledge, this is the first meta-analysis using high-throughput sequencing data, providing a valuable starting point for future rectal cancer research.