Homo sapiens Transcriptome or Gene expression

Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer (LARC). Pathological complete regression (pCR) is closely linked to outcomes. However, biomarkers predicting nCRT response and survival are lacking in LARC. A total of 228 patients with locally advanced rectal cancer with clinical characteristics and follow-up information were retrospectively collected for the present study. Immunohistochemistry (IHC), reverse transcription-quantitative PCR (RT-qPCR), and Kaplan-Meier (K-M) and multivariate analysis were used to evaluate the expression and predict the role of CKLF-like Marvel transmembrane domain member 4 (CMTM4) in LARC. Lentivirus shRNA is used to interfere with CMTM4 expression. The phenotype of CMTM4-knockdown LoVo cells was determined by colony formation, migration and invasion assays under Iron Radiation (IR) treatment. RNA-seq analysis was used to explore CMTM4-regulated genes in LoVo-shCMTM4 cells compared with control cells. RT-qPCR was used to confirm the CMTM4-regulated genes. CMTM4 expression in pre-nCRT tissues indicated an unfavorable response and short disease-free survival (DFS) in patients with LARC. The expression of CMTM4 significantly increased following nCRT treatment. CMTM4 knockdown increased cell proliferation, migration and invasion. Radiation disrupted the cell migration and invasion induced by CMTM4 knockdown. RNA-seq analysis, Tumor Immune Estimation Resource database and RT-qPCR indicated that CMTM4 was involved in different signalling pathways and regulated immune-related genes cluster of differentiation 66b (CD66b), chemokine (CXC motif) ligand 8 (CXCL8) and programmed cell death 1(PD1). Furthermore, CXCL8 expression was found to be negatively correlated with CMTM4 in patients with LARC by IHC and RT-qPCR. CXCL8 expression on invasion margin regions in post-operative tissues was an inferior predictor of DFS in patients with LARC. In conclusion, CMTM4 may predict neoadjuvant chemoradiotherapy response and outcomes in patients with LARC.