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

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497846PMC
http://dx.doi.org/10.1158/1535-7163.MCT-18-0694DOI Listing

Publication Analysis

Top Keywords

tumor sidedness
12
cetuximab treatment
12
metastatic colorectal
8
colorectal cancer
8
response cetuximab
8
gene set
8
[logcpm ≥
8
favorable survival
8
gene
6
cetuximab
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!