Profiling Neoadjuvant Therapy Response in Rectal Cancer Using Publicly Available Transcriptomic RNA-seq Datasets

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 RNAseq data to identify predictive features of response. TRIM54 and PABPC4 were up-regulated in the responder group, while ADSS1 and MGAT1 were up-regulated in non-responder group. ARMC2 was identified as a predictive biomarker up-regulated 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 responder group. SMAD3 and RDXANK were associated with complete regression, while MYC was dominant in incomplete regression. These findings provided 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.