Profiling neoadjuvant therapy response in rectal cancer using meta‐analysis of publicly available transcriptomic <scp>RNA</scp> ‐seq datasets

<jats:p> 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. <jats:italic>TRIM54</jats:italic> and <jats:italic>PABPC4</jats:italic> were upregulated in the responder group, while <jats:italic>ADSS1</jats:italic> and <jats:italic>MGAT1</jats:italic> were upregulated in the non‐responder group. <jats:italic>ARMC2</jats:italic> 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 <jats:italic>SP1</jats:italic> and <jats:italic>NFKB</jats:italic> activations in the non‐responder group and <jats:italic>TCF15</jats:italic> in the responder group. <jats:italic>SMAD3</jats:italic> and <jats:italic>RDXANK</jats:italic> were associated with complete regression, while <jats:italic>MYC</jats:italic> 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. </jats:p>