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MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.

ABSTRACT: BACKGROUND:Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC). RESULTS:We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search. The Ingenuity Pathway Analysis (IPA) analysis identified additional genes that are functionally related to the 36 focus genes through pathway relationships yielding a total of 82 genes. Subsequently, 800 SNPs within the 82 IPA-selected genes on the Illumina HumanOmniExpress-12v1 platform were selected from a large-scale genotyping effort. Association analyses between the 800 candidate SNPs (covering 82 genes) and pain in a patient cohort of 1368 patients with HNSCC (206 patients with severe pain vs. 1162 with non-severe pain) showed the highest significance for MAPK1/ERK2, a gene belonging to the MAP kinase family (rs8136867, p value = 8.92 × 10(-4); odds ratio [OR]?= 1.33, 95 % confidence interval [CI]: 1.13-1.58). Other top genes were PIK3C2G (a member of PI3K [complex], rs10770367, p value = 1.10 × 10(-3); OR = 1.46, 95 % CI: 1.16-1.82), TCRA (the alpha chain of T-cell receptor, rs6572493, p value = 2.84 × 10(-3); OR = 0.70, 95 % CI: 0.55-0.88), PDGFC (platelet-derived growth factor C, rs6845322, p value = 4.88 × 10(-3); OR = 1.32, 95 % CI: 1.09-1.60), and CD247 (a member of CD3, rs2995082, p value = 7.79 × 10(-3); OR = 0.76, 95 % CI: 0.62-0.93). CONCLUSIONS:Our findings provide novel candidate genes and biological pathways underlying pain in cancer patients. Further study of the variations of these candidate genes could inform clinical decision making when treating cancer pain.

SUBMITTER: Reyes-Gibby CC

PROVIDER: S-EPMC4752805 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.

Reyes-Gibby Cielito C CC Wang Jian J Silvas Mary Rose T MR Yu Robert R Yeung Sai-Ching J SC Shete Sanjay S

BMC genetics 20160213

<h4>Background</h4>Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC).<h4>Results</h4>We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search. The In ...[more]

PMID: 26872611

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Project description:Head and neck cancer (HNC) is the sixth most common cancer worldwide. Recent studies on the pathogenesis of HNC have identified some biochemical associations of this disease, but the molecular mechanisms are not clear. To explore the genetic alterations in head and neck tumors, to identify new high-specificity and high-sensitivity tumor markers, and to investigate potentially effective therapeutic targets, in silico methods were used to study HNC. The GSE58911 microarray dataset was downloaded from the Gene Expression Omnibus online database to identify potential target genes in the carcinogenesis and progression of HNC. Differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. In addition, a protein-protein interaction network was also constructed, and gene analysis was undertaken using Search Tool for the Retrieval of Interacting Genes and Cytoscape. A total of 648 differentially expressed genes were identified. Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology functional enrichment analysis of DEGs included muscle system process, extracellular matrix organization, actin binding, structural molecule activity, structural constituent of muscle, extracellular region part, ECM-receptor interaction, amoebiasis, focal adhesion, drug metabolism-cytochrome P450, and chemical carcinogenesis. There were 26 hub genes identified and biological process analysis revealed that these genes were mainly enriched in extracellular matrix organization, serine-type endopeptidase activity, extracellular matrix, and complement and coagulation cascades. Survival analysis revealed that interleukin (IL)-8 (C-X-C motif chemokine ligand 8), IL1B, and serpin family A member 1 may be involved in the carcinogenesis of HNC. In summary, the DEGs and hub genes identified in the present study may increase understanding of the molecular mechanisms of development of HNC and provide potential target genes for clinical diagnosis and targeted therapy.

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MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.

Publications

MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients.

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