Dataset Information

TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of Functional Assay.

ABSTRACT: Objective: Bone metastasis from patients with advanced lung adenocarcinoma (LAC) is a very serious complication. To better understand the molecular mechanism, our current study sheds light on identification of hub genes mediating bone metastatic spread by combining bioinformatic analysis with functional verification. Methods: First, we downloaded a lung adenocarcinoma dataset (GSE76194) from Gene Expression Omnibus, analyzed differentially expressed genes (DEGs) through Limma package in R software and constructed a protein-protein interaction network. Based on that preliminary data, we further performed modular and topological analysis using Cystoscope to obtain biological connected genes. Through literature searching and performing mRNA expression analysis on the other independent public dataset (GSE10799), we finally focused on TBX2. Functional effects of TBX2 were performed in tumorigenicity assays including migration and invasion assays, cell proliferation assay, and cell cycle assay. In addition, mechanically, we found enriched pathways related to bone metastasis using Gene Set Enrichment Analysis (GSEA) and validated our results by western blot. Result: A total of 1132 significant genes were sorted initially. We selected common significant genes (log FC>2; p<0.01) from both the biological network data and microarray data. In total, 44 such genes were identified. we found TBX2, along with 10 other genes, to be reported with relevance to bone metastasis in other cancer types. Moreover, TBX2 showed significantly higher expression levels in patients that were found positive for metastasis to bone marrow compared to patients that did not exhibit this type of metastasis in the other separated cohort (GSE10799). Thus, we finally focused on TBX2. We found that TBX2 had detectable expression in LAC cell lines and silencing endogenous TBX2 expression in A549 and H1299 cell lines markedly suppressed migration and invasion, cell proliferation and arrested cell-cycle. Pathway enrichment analyses suggested that TBX2 drove LAC oncogenesis and metastasis through various pathways with epithelial mesenchymal transition (EMT) figuring prominently in the bone metastatic group, which was evidenced by western blot. Conclusion: Collectively, TBX2 plays as a potential predictor of bone metastasis from LAC, yielding a better promise view towards "driver" gene responsible for bone metastasis.

SUBMITTER: Yu H

PROVIDER: S-EPMC6930436 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of Functional Assay.

Yu Huajian H Zhao Fangyu F Li Jing J Zhu Kechao K Lin Hechun H Pan Zhen Z Zhu Miaoxin M Yao Ming M Yan Mingxia M

Journal of Cancer 20200101 2

<b>Objective:</b> Bone metastasis from patients with advanced lung adenocarcinoma (LAC) is a very serious complication. To better understand the molecular mechanism, our current study sheds light on identification of hub genes mediating bone metastatic spread by combining bioinformatic analysis with functional verification. <b>Methods:</b> First, we downloaded a lung adenocarcinoma dataset (GSE76194) from Gene Expression Omnibus, analyzed differentially expressed genes (DEGs) through Limma packa ...[more]

PMID: 31897234

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Project description:Hepatocellular carcinoma (HCC) is a typical inflammation-driven cancer. Chronically unresolved inflammation may remodel the immunosuppressive tumor microenvironment, which is rich in innate immune cells. The mechanisms via which HCC progresses through the evasion of the innate immune surveillance remain unclear. The present study thus aimed to identify key genes involved in HCC immunosuppression and to establish an innate immune risk signature, with the ultimate goal of obtaining new insight into effective immunotherapies. HCC and normal liver tissue mRNA expression and clinicopathological data were obtained from the Cancer Genome Atlas database. The immunosuppressive innate immune-related genes (IIRGs) in HCC were screened using integrated bioinformatics analyses. Gene expression was then validated using the Gene Expression Omnibus database and the Human Protein Atlas database, and tissues were obtained from patients with HCC who underwent surgery. In total, 3,676 genes were identified as differentially expressed mRNAs after comparing the HCC tissues with the normal liver tissues in TCGA. Gene Set Enrichment Analyses revealed 21 highly expressed IIRGs in HCC tissues. A survival analysis and Cox regression model were used to construct an innate immune risk signature, including three IIRGs: Collectin-12 (COLEC12), matrix metalloproteinase-12 (MMP12) and mucin-12 (MUC12) genes. Univariate and multivariate Cox analyses revealed that the signature of the three IIRGs was a robust independent risk factor in relation to the overall survival (OS) of patients with HCC. The expression of the three aforementioned IIRGs was confirmed through external validation. Moreover, COLEC12 and MMP12 expression significantly correlated with that of immune checkpoint molecules or immunosuppressive cytokines. The tumor immune dysfunction and exclusion tool predicted that the increased expression of the three IIRGs in patients with HCC was significantly associated with the efficacy of relatively poor immune checkpoint blockade therapy. Conclusively, a novel innate immune-related risk signature for patients with HCC was constructed and validated. This signature may be involved in immunosuppression, and may be used to predict a poor prognosis, functioning as a potential immunotherapeutic target for patients with HCC.

Dataset Information

TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of Functional Assay.

Publications

TBX2 Identified as a Potential Predictor of Bone Metastasis in Lung Adenocarcinoma via Integrated Bioinformatics Analyses and Verification of Functional Assay.

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