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Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis.

作者信息

Ni Mengwei, Liu Xinkui, Wu Jiarui, Zhang Dan, Tian Jinhui, Wang Ting, Liu Shuyu, Meng Ziqi, Wang Kaihuan, Duan Xiaojiao, Zhou Wei, Zhang Xiaomeng

机构信息

Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

出版信息

Front Genet. 2018 Oct 12;9:469. doi: 10.3389/fgene.2018.00469. eCollection 2018.

DOI:10.3389/fgene.2018.00469
PMID:30369945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6194157/
Abstract

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all patients with lung cancer and 5-year relative overall survival (OS) rate is less than 20%, so that identifying novel diagnostic and prognostic biomarkers is urgently demanded. The present study attempted to identify potential key genes associated with the pathogenesis and prognosis of NSCLC. Four GEO datasets (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NSCLC samples and normal ones were analyzed using limma package, and RobustRankAggreg (RRA) package was used to conduct gene integration. Moreover, Search Tool for the Retrieval of Interacting Genes database (STRING), Cytoscape, and Molecular Complex Detection (MCODE) were utilized to establish protein-protein interaction (PPI) network of these DEGs. Furthermore, functional enrichment and pathway enrichment analyses for DEGs were performed by Funrich and OmicShare. While the expressions and prognostic values of top genes were carried out through Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan Meier-plotter (KM) online dataset. A total of 249 DEGs (113 upregulated and 136 downregulated) were identified after gene integration. Moreover, the PPI network was established with 166 nodes and 1784 protein pairs. Topoisomerase II alpha , a top gene and hub node with higher node degrees in module 1, was significantly enriched in mitotic cell cycle pathway. In addition, Interleukin-6 ) was enriched in amb2 integrin signaling pathway. The mitotic cell cycle was the most significant pathway in module 1 with the highest -value. Besides, five hub genes with high degree of connectivity were selected, including , and , and they were all correlated with worse OS in NSCLC. The results showed that , and may be potential key genes, while the mitotic cell cycle pathway may be a potential pathway contribute to progression in NSCLC. Further, it could be used as a new biomarker for diagnosis and to direct the synthesis medicine of NSCLC.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/6be99bbb0910/fgene-09-00469-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/8090ae2eb87a/fgene-09-00469-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/fb8e6b6f3c50/fgene-09-00469-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/0af5fea39eae/fgene-09-00469-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/d4cd59ac102a/fgene-09-00469-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/9cf86933ca97/fgene-09-00469-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/aa9e322790a9/fgene-09-00469-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/678ddd2193ea/fgene-09-00469-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/054824c71cc6/fgene-09-00469-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/5da767c08e8b/fgene-09-00469-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/6be99bbb0910/fgene-09-00469-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/8090ae2eb87a/fgene-09-00469-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/fb8e6b6f3c50/fgene-09-00469-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/0af5fea39eae/fgene-09-00469-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/d4cd59ac102a/fgene-09-00469-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/9cf86933ca97/fgene-09-00469-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/aa9e322790a9/fgene-09-00469-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/678ddd2193ea/fgene-09-00469-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/054824c71cc6/fgene-09-00469-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/5da767c08e8b/fgene-09-00469-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61b/6194157/6be99bbb0910/fgene-09-00469-g010.jpg

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[8]
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[9]
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[10]
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本文引用的文献

[1]
Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC.

J Thorac Oncol. 2018-7-5

[2]
Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer.

Int J Cancer. 2018-9-21

[3]
Unraveling the role of low-frequency mutated genes in breast cancer.

Bioinformatics. 2019-1-1

[4]
Dichloroacetate enhances the antitumor efficacy of chemotherapeutic agents via inhibiting autophagy in non-small-cell lung cancer.

Cancer Manag Res. 2018-5-16

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Expression of metastasis-associated lung adenocarcinoma transcript 1 long non-coding RNA and in patients with non-small cell lung cancer.

Oncol Lett. 2018-6

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A real-world study of treatment patterns and survival outcome in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer.

Oncol Lett. 2018-6

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Identification of potential diagnostic and prognostic biomarkers in non-small cell lung cancer based on microarray data.

Oncol Lett. 2018-5

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Identification of a five-lncRNA signature for predicting the risk of tumor recurrence in patients with breast cancer.

Int J Cancer. 2018-7-28

[9]
Identification of Common Genes Refers to Colorectal Carcinogenesis with Paired Cancer and Noncancer Samples.

Dis Markers. 2018-1-30

[10]
Non-small-cell lung cancer pathological subtype-related gene selection and bioinformatics analysis based on gene expression profiles.

Mol Clin Oncol. 2018-2

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