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Identification of differentially expressed genes in small and non-small cell lung cancer based on meta-analysis of mRNA.

ABSTRACT: Lung cancer has the lowest survival rate spread globally resulting in a large number of deaths. This is attributed to insufficient measures such as lack of early detection and chemoresistance in the patients. It can be subdivided into two histological groups: Non-Small-Cell Lung Cancer (NSCLC), which is most prevalent (85% of all lung cancers) but less destructive; and Small-Cell Lung Cancer (SCLC), which is intermittently metastatic and less prevalent (15% of all lung cancers). The present study deals with the analysis of gene expression of two subtypes to identify the Differentially Expressed Genes (DEGs). For this study, we selected two datasets from the Omnibus database, which included 50 non-small cell lung cancer samples, 31 small cell lung cancer samples, and 48 samples from normal lung tissue. After DEGs identification using the meta-analysis approach, they were then subjected to further analysis following p-value adjustment via the Benjamini-Hochberg method. We identified 440 overexpressed and 489 underexpressed genes in NSCLC, and 489 overexpressed and 525 underexpressed genes in SCLC, compared with normal lung tissues. Furthermore, we identified 3 overlapping genes between upregulated DEGs in NSCLC and downregulated DEGs in SCLC; and 8 overlapping genes between upregulated DEGs in SCLC and downregulated DEGs in NSCLC. Accordingly, a Protein-Protein Interaction (PPI) network of the overlapping genes was generated, which contained a total of 261 genes, of which the top five were TRIM29, ANK3, CSTA, FGG, and AGR2. These five candidate genes reported herein may prove to be potential therapeutic targets.

SUBMITTER: Shriwash N

PROVIDER: S-EPMC6580189 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Identification of differentially expressed genes in small and non-small cell lung cancer based on meta-analysis of mRNA.

Shriwash Nitesh N Singh Prithvi P Arora Shweta S Ali Syed Mansoor SM Ali Sher S Dohare Ravins R

Heliyon 20190614 6

Lung cancer has the lowest survival rate spread globally resulting in a large number of deaths. This is attributed to insufficient measures such as lack of early detection and chemoresistance in the patients. It can be subdivided into two histological groups: Non-Small-Cell Lung Cancer (NSCLC), which is most prevalent (85% of all lung cancers) but less destructive; and Small-Cell Lung Cancer (SCLC), which is intermittently metastatic and less prevalent (15% of all lung cancers). The present stud ...[more]

PMID: 31338439

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Project description:Non-small cell lung cancer (NSCLC) is a major cause of cancer-associated mortality worldwide, and bone metastasis is the most prevalent event observed in patients with advanced NSCLC. However, the pathogenesis of bone metastases has not been fully elucidated. In the present study, differentially expressed genes (DEGs) were identified by gene expression microarray analysis of NSCLC tissue samples with or without bone metastases. Subsequently, collagen type 6A1 (COL6A1) was chosen as the target gene through Ingenuity Pathway Analysis and reverse transcription-quantitative (RT-q) PCR validation of the top eight DEGs. COL6A1 was overexpressed or knocked down, and the proliferation and invasion of NSCLC cells was assessed using Cell Counting Kit-8, colony formation and Transwell invasion assays. Additionally, the osteogenic capacity of HOB and hES-MP 002.5 cells was assessed using RT-qPCR, western blotting, Alizarin Red and alkaline phosphatase staining. A total of 364 DEGs were identified in NSCLC tissues with bone metastases compared with NSCLC tissues without bone metastases, including 140 upregulated and 224 downregulated genes. Gene Ontology analysis results demonstrated that the upregulated and downregulated genes were primarily enriched in 'cellular process', 'metabolic process' and 'biological regulation'. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the upregulated genes were primarily enriched in 'cysteine and methionine metabolism', 'oxidative phosphorylation' and 'ribosome', whereas the downregulated genes were primarily enriched in the 'transcriptional misregulation in cancer', 'ribosome' and 'mitophagy-animal' pathways. COL6A1 was highly expressed in NSCLC tissue samples with bone metastases. Functionally, COL6A1 overexpression induced the proliferation and invasion of HARA cells, and its knockdown inhibited the proliferation and invasion of HARA-B4 cells. Finally, it was demonstrated that HOB and hES-MP 002.5 cells exhibited osteogenic capacity, and overexpression of COL6A1 in HARA cells increased the adhesion of these cells to the osteoblasts, whereas knockdown of COL6A1 in HARA-B4 cells reduced their adhesive ability. In conclusion, COL6A1 may serve as a potential diagnostic marker and therapeutic target for bone metastasis in NSCLC.

Project description:Non-small cell lung cancer (NSCLC) is a leading cause of mortality worldwide. However, the pathogenesis of NSCLC remains to be fully elucidated. Therefore, the present study aimed to explore the differential expression of mRNAs and microRNAs (miRNAs/miRs) in NSCLC and to determine how these RNA molecules interact with one another to affect disease progression. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified from the GSE18842, GSE32863 and GSE29250 datasets downloaded from the Gene Expression Omnibus (GEO database). Functional and pathway enrichment analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. STRING, Cytoscape and MCODE were applied to construct a protein-protein interaction (PPI) network and to screen hub genes. The interactions between miRNAs and mRNAs were predicted using miRWalk 3.0 and a miRNA-mRNA regulatory network was constructed. The prognostic value of the identified hub genes was then evaluated via Kaplan-Meier survival analyses using datasets from The Cancer Genome Atlas. A total of 782 DEGs and 46 DEMs were identified from the 3 GEO datasets. The enriched pathways and functions of the DEGs and target genes of the DEMs included osteoclast differentiation, cell adhesion, response to a drug, plasma membrane, extracellular exosome and protein binding. A subnetwork composed of 11 genes was extracted from the PPI network and the genes in this subnetwork were mainly involved in the cell cycle, cell division and DNA replication. A miRNA-gene regulatory network was constructed with 247 miRNA-gene pairs based on 6 DEMs and 210 DEGs. Kaplan-Meier survival analysis indicated that the expression of ubiquitin E2 ligase C, cell division cycle protein 20, DNA topoisomerase II?, aurora kinase A and B, cyclin B2, maternal embryonic leucine zipper kinase, slit guidance ligand 3, phosphoglucomutase 5, endomucin, cysteine dioxygenase type 1, dihydropyrimidinase-like 2, miR-130b, miR-1181 and miR-127 was significantly associated with overall survival of patients with lung adenocarcinoma. In the present study, a miRNA-mRNA regulatory network in NSCLC was established, which may provide future avenues for scientific exploration and therapeutic targeting of NSCLC.

Dataset Information

Identification of differentially expressed genes in small and non-small cell lung cancer based on meta-analysis of mRNA.

Publications

Identification of differentially expressed genes in small and non-small cell lung cancer based on meta-analysis of mRNA.

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