Mingrui Shao1, Shize Yang1, Siyuan Dong1. 1. Department of Thoracic Surgery, The first hospital of China Medical University, Shenyang, Liaoning, China.
Abstract
BACKGROUNDS: Lung adenocarcinoma is a complex disease that results in over 1.8 million deaths a year. Recent advancements in treating and managing lung adenocarcinoma have led to modest decreases in associated mortality rates, owing in part to the multifactorial etiology of the disease. Novel prognostic biomarkers are needed to accurately stage the disease and act as the basis of adjuvant treatments. MATERIAL AND METHODS: The microarray datasets GSE75037, GSE31210 and GSE32863 were downloaded from the Gene Expression Omnibus (GEO) database to identify prognostic biomarkers for lung adenocarcinoma and therapy. The differentially expressed genes (DEGs) were identified by GEO2R. Functional and pathway enrichment analysis were performed by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). Validation was performed based on 72 pairs of lung adenocarcinoma and adjacent normal lung tissues. RESULTS: Results showed that the DEGs were mainly focused on cell cycle and DNA replication initiation. Forty-one hub genes were identified and further analyzed by CytoScape. Here, we provide evidence which suggests MCM10 is a potential target with prognostic, diagnostic and therapeutic value. We base this on an integrated approach of comprehensive bioinformatics analysis and in vitro validation using the A549 lung adenocarcinoma cell line. We show that MCM10 overexpression correlates with a poor prognosis, while silencing of this gene decreases aberrant growth by 2-fold. Finally, evaluation of 72 clinical biopsy samples suggests that overexpression of MCM10 in the lung adenocarcinoma highly correlates with larger tumor size. Together, this work suggests that MCM10 may be a clinically relevant gene with both predictive and therapeutic value in lung adenocarcinoma.
BACKGROUNDS: Lung adenocarcinoma is a complex disease that results in over 1.8 million deaths a year. Recent advancements in treating and managing lung adenocarcinoma have led to modest decreases in associated mortality rates, owing in part to the multifactorial etiology of the disease. Novel prognostic biomarkers are needed to accurately stage the disease and act as the basis of adjuvant treatments. MATERIAL AND METHODS: The microarray datasets GSE75037, GSE31210 and GSE32863 were downloaded from the Gene Expression Omnibus (GEO) database to identify prognostic biomarkers for lung adenocarcinoma and therapy. The differentially expressed genes (DEGs) were identified by GEO2R. Functional and pathway enrichment analysis were performed by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO). Validation was performed based on 72 pairs of lung adenocarcinoma and adjacent normal lung tissues. RESULTS: Results showed that the DEGs were mainly focused on cell cycle and DNA replication initiation. Forty-one hub genes were identified and further analyzed by CytoScape. Here, we provide evidence which suggests MCM10 is a potential target with prognostic, diagnostic and therapeutic value. We base this on an integrated approach of comprehensive bioinformatics analysis and in vitro validation using the A549 lung adenocarcinoma cell line. We show that MCM10 overexpression correlates with a poor prognosis, while silencing of this gene decreases aberrant growth by 2-fold. Finally, evaluation of 72 clinical biopsy samples suggests that overexpression of MCM10 in the lung adenocarcinoma highly correlates with larger tumor size. Together, this work suggests that MCM10 may be a clinically relevant gene with both predictive and therapeutic value in lung adenocarcinoma.
Authors: Luc Girard; Jaime Rodriguez-Canales; Carmen Behrens; Debrah M Thompson; Ihab W Botros; Hao Tang; Yang Xie; Natasha Rekhtman; William D Travis; Ignacio I Wistuba; John D Minna; Adi F Gazdar Journal: Clin Cancer Res Date: 2016-06-28 Impact factor: 12.531
Authors: Gregory M M Videtic; Larry W Stitt; A Rashid Dar; Walter I Kocha; Anna T Tomiak; Pauline T Truong; Mark D Vincent; Edward W Yu Journal: J Clin Oncol Date: 2003-04-15 Impact factor: 44.544
Authors: Suhaida A Selamat; Brian S Chung; Luc Girard; Wei Zhang; Ying Zhang; Mihaela Campan; Kimberly D Siegmund; Michael N Koss; Jeffrey A Hagen; Wan L Lam; Stephen Lam; Adi F Gazdar; Ite A Laird-Offringa Journal: Genome Res Date: 2012-05-21 Impact factor: 9.043