Tumor Sidedness and Enriched Gene Groups for Efficacy of First-line Cetuximab Treatment in Metastatic Colorectal Cancer

摘要: Molecular differences in tumor locations may contribute to the sidedness-specific response cetuximab metastatic colorectal cancer (mCRC). We investigated genes associated with treatment depending on sidedness. Our study included 77 patients mCRC (13/63, right/left) KRAS exon 2 wild-type tumors from phase II trials of first-line therapy cetuximab. Expression levels 2,551 were measured tissue samples by HTG EdgeSeq Oncology Biomarker Panel. Univariate Cox regression analysis using log2 values counts per million (CPM) was conducted each sidedness assess associations clinical outcomes, and define optimal cut-off point for clinically significant genes. In addition, a gene set enrichment (GSEA) performed identify pathways Sixty-nine assessable expression data. Overexpression BECN1 [log2(CPM) ≥ 6.8] favorable survival, regardless High NOTCH1 7.5] predicted significantly longer progression-free survival (PFS; median 14.7 vs. 11.1 months, HR 0.43, P = 0.01) overall (OS; 42.8 26.5 0.35, left side but not right side. The GSEA showed that regulation DNA replication correlated left, whereas subcellular component leukocyte migration sets good right. conclusion, contributing efficacy differ according mCRC. potentially discriminate responders left-sided tumors.