Candidate genes and potential mechanisms for chemoradiotherapy sensitivity in locally advanced rectal cancer

Chunsheng Li; Changyong E; Yangyang Zhou; Wei Yu

doi:10.3892/ol.2019.10087

Candidate genes and potential mechanisms for chemoradiotherapy sensitivity in locally advanced rectal cancer

Oncol Lett. 2019 May;17(5):4494-4504. doi: 10.3892/ol.2019.10087. Epub 2019 Feb 28.

Authors

Chunsheng Li¹, Changyong E², Yangyang Zhou³, Wei Yu¹

Affiliations

¹ Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
² Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
³ Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract

The aim of the present study was to investigate candidate genes for chemoradiotherapy (CRT) sensitivity in patients with locally advanced rectal cancer (LARC), and the potential mechanisms of their action. A microarray dataset (GSE98959) was obtained from the Gene Expression Omnibus database that included microRNA (miRNA, miR) expression profiling of 22 samples from patients with LARC who had received preoperative radiotherapy and chemotherapy. Of these patients, 10 responded to the treatment and 12 did not. Differentially expressed miRNAs (DEMs) were identified, followed by the construction of an miRNA-gene network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) function analyses were performed on the target genes in the miRNA-gene network. Furthermore, a protein-protein interaction (PPI) network was constructed on the basis of the target genes, followed by GO function enrichment and KEGG pathway analysis. A total of 30 DEMs were identified between the responder and non-responder groups. Thiamine metabolism (including miR-371a-3p) was the pathway with the highest enrichment of DEMs. The pathway that was most markedly enriched in the target genes of upregulated miRNAs was the pluripotency of stem cells pathway, as indicated by phosphoinositide-4,5-bisphosphate 3-kinase γ (PIK3CG) and anaphase-promoting complex subunit 2 (APC2). Pathways in cancer exhibited the highest enrichment in the set of target genes of downregulated miRNAs. KEGG pathway and GO function analysis indicated that target genes in the PPI network were enriched in the glioma pathway and assembled in the intracellular signaling cascade function, as indicated by the proto-oncogene NRAS. miR-371a-3p may be a candidate miRNA for CRT sensitivity in LARC via the thiamine metabolism pathway. PIK3CG and APC2 may contribute to CRT sensitivity via signaling pathways regulating the pluripotency of stem cells. Furthermore, NRAS may serve an important role in mediating CRT sensitivity via an intracellular signaling cascade.

Keywords: chemoradiotherapy sensitivity; function and pathway analysis; locally advanced rectal cancer; microRNA-gene regulation network; protein-protein interaction network.