Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

Abstract

Background: Lung squamous cell carcinoma (lung SCC) is a common type of malignancy. Its pathogenesis mechanism of tumor development is unclear. The aim of this study was to identify key genes for diagnosis biomarkers in lung SCC metastasis. Methods: We searched and downloaded mRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify differences in mRNA expression of primary tumor tissues from lung SCC with and without metastasis. Gene co-expression network analysis, protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and quantitative real-time polymerase chain reactions (qRT-PCR) were used to explore the biological functions of the identified dysregulated genes.Results: Four hundred and eighty-two differentially expressed genes (DEGs) were identified between lung SCC with and without metastasis. Nineteen modules were identified in lung SCC through weighted gene co-expression network analysis (WGCNA). Twenty-three DEGs and 26 DEGs were significantly enriched in the respective pink and black module. KEGG pathway analysis displayed that 26 DEGs in the black module were significantly enriched in bile secretion pathway. Forty-nine DEGs in the two gene co-expression module were used to construct PPI network. CFTR in the black module was the hub protein, had the connectivity with 182 genes. The results of qRT-PCR displayed that FIGF, SFTPD, DYNLRB2 were significantly down-regulated in the tumor samples of lung SCC with metastasis and CFTR, SCGB3A2, SSTR1, SCTR, ROPN1L had the down-regulation tendency in lung SCC with metastasis compared to lung SCC without metastasis. Conclusions: The dysregulated genes including CFTR, SCTR and FIGF might be involved in the pathology of lung SCC metastasis and could be used as potential diagnosis biomarkers or therapeutic targets for lung SCC. IntroductionLung squamous cell carcinoma (lung SCC) is a histological subtype of non-small cell lung cancer (NSCLC), which is the second most frequent type of NSCLC after lung adenocarcinoma (1). Lung SCC is a multi-step progressive disease with high rates of morbidity and mortality worldwide.The initiation of lung SCC is divided into the following five successive stages: normal bronchial epithelium, squamous metaplasia, mild-moderate dysplasia, carcinoma in situ, and invasive carcinoma (2). The prognosis of lung cancer is unfavorable, despite significant therapeutic improvements have been made in recent years. In current, there is no specific molecular targets for therapy have been identified (3), therefore, cisplatin plus gemcitabine is still the first-line treatment for lung SCC (4).Currently, the tumorigenesis mechanism of lung SCC remains unclear. Numerous published articles demonstrate that dysregulated genes are essential for initiation, progression and development of lung cancer. SMC4 (structural maintenance of chromosome 4) is over-expressed in lung adenocarcinoma tissues and its inhibition significantly suppresses the prolif...

Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA)

“…It relies on the assumption that highly correlated genes within a module are involved in common biological processes. For example, Tian et al [13] used WGCNA to identify two gene co-expression modules involved in the process of lung SCC metastasis and suggested that CFTR, SCTR, and FIGF genes could be used as a potential prognostic biomarker. Using WGCNA in the studies of progression and prognosis of breast cancer indicated the relevant correlation of one module of genes with patient survival time.…”

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“…ROPN1L variants are significantly associated with high risk of breast cancer in women [31]. Moreover, Tian et al reported that ROPN1L was enriched in lung squamous cell carcinoma [32]. Lowe et al [33] showed that ROPN1L gene was overexpressed in pancreatic cancer.…”

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