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Comprehensive genomic and prognostic analysis of the IL17 family genes in lung cancer

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The six members of the interleukin (IL)17 gene family (IL17AF) have been identified in various types of cancer. Although lung cancer is the leading cause of cancerrelated death worldwide and IL17A was found to play a critical role in lung cancer, there is little knowledge concerning the association between the other five members of the IL17 family and lung cancer. The genetic mutations and expression of IL17 family members were investigated using the Catalogue of Somatic Mutations in Cancer (COSMIC), Oncomine, and cBio Cancer Genomics Portal (cBioPortal) databases. Prognostic values and interaction networks of the members were assessed by the KaplanMeier plotter, Search Tool for the Retrieval of Interacting Genes (STRING) database and FunRich software. The results found that, across 5,238 lung cancer patients in the cBioPortal, the results of IL17 family gene alteration frequencies and types showed that IL17A, IL25 and IL17F exhibited higher alteration frequencies (2, 2.1 and 1.9%, respectively), and gene amplification accounted for the majority of changes. IL17B, IL17C and IL17D exhibited lower alteration frequencies (0.8, 1.1 and 1.1%, respectively), and deep deletion accounted for the majority of changes. The rates of point mutations in IL17A through IL17F family genes in lung cancer were 0.66, 0.18, 0.13, 0.09, 0.27 and 0.44% in the COSMIC database. Within the Oncomine database, five datasets showed that IL17D was significantly decreased in lung cancer, while no dataset showed a significant difference in the expression of IL17A, IL17B, IL17C, IL25 or IL17F between lung cancer and normal controls. The frequencies of IL17A, IL17B and IL17C mRNA upregulation in lung squamous cell carcinoma were lower than those in lung adenocarcinoma (2.7, 1.9 and 2.1%, respectively), whereas the frequencies of IL17D, IL25 and IL17F mRNA upregulation were higher in lung squamous cell carcinoma than those in lung adenocarcinoma (3, 6 and 6%, respectively). IL17A and IL17B were unrelated to overall survival (p=0.11; P=0.17), whereas IL17C, IL17D, IL25 and IL17F influenced prognosis (P=0.0023, P=0.0059, P=0.039 and P=0.0017, respectively) according to the KaplanMeier plotter. Moreover, the expression level of IL17C was the highest in lung tissues, and IL17 family genes mainly participate in the ‘IFNγ pathway’ according to the STRING database and Funrich software. In conclusion, we performed the first comprehensive investigation of the IL17 gene family in lung cancer, including gene mutation, mRNA expression levels, prognostic values and network pathways. Our results revealed that IL17 family gene mutation rates were in general low and that amplification and deep deletion were the main mutation type. The expression and function of IL17A and IL17B in lung cancer are still not fully elucidated and warrant research with larger sample sizes. IL17D was significantly decreased in lung cancer and was correlated with better OS. Studies of IL17CF in lung cancer are limited. Further experimental studies on the association between IL17D and lung cancer progression are needed to identify more effective therapeutic targets for lung cancer.
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Document Type: Research Article

Affiliations: 1: Key Laboratory of Respiratory Diseases of the Ministry of Health, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China 2: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China

Publication date: June 1, 2019

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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