Dataset Information

Prognostic significance of KRT19 in Lung Squamous Cancer.

ABSTRACT: Backgroud: Keratin 19 (KRT19) is the intermediate filament that constitutes the cytoskeleton and regulates cell-cycle and cell death. Objective: We aimed to assess whether KRT19 was involved in lung cancer development. Methods: The expression of KRT19 in lung cancer was evaluated from mRNA expression on open databse and protein abundance on tumor tissue array. Results: Using open microarray gene expression datasets and differential expression analysis, we found that KRT19 was upregulated in lung cancer compared with normal tissue. Further analysis suggested that KRT19 mRNA expression was correlated with tumor progression and overall survival in lung cancer patients. As KRT19 was overexpressed in adenocarcinoma (AC) and squamous cell carcinoma (SCC), we examined the prognostic value of KRT19 protein abundance by tissue microarray (TMA). The results suggested that protein expression of KRT19 was significantly associated with overall survival of SCC. Conclusions: Giving the prognostic role of KRT19 in lung cancer, KRT19 could be considered as an potential molecular marker in lung cancer, especially in SCC.

SUBMITTER: Yuan X

PROVIDER: S-EPMC7797641 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Prognostic significance of KRT19 in Lung Squamous Cancer.

Yuan Xun X Yi Ming M Dong Bing B Chu Qian Q Wu Kongming K

Journal of Cancer 20210101 4

Backgroud: Keratin 19 (KRT19) is the intermediate filament that constitutes the cytoskeleton and regulates cell-cycle and cell death. Objective: We aimed to assess whether KRT19 was involved in lung cancer development. Methods: The expression of KRT19 in lung cancer was evaluated from mRNA expression on open databse and protein abundance on tumor tissue array. Results: Using open microarray gene expression datasets and differential expression analysis, we found that K ...[more]

PMID: 33442422

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Project description:IntroductionFAS has been implicated in the development of various cancers, but its involvement in lung cancer has not been systematically characterized. In this study, we performed data mining in online tumor databases to investigate the expression, methylation, alterations, protein interactions, co-expression and prognostic significance of FAS in lung cancer.MethodThe expression, prognostic significance and molecular interactions of FAS in lung cancer was mined and analyzed using GENT2, GEPIA2, UALCAN, cBioPortal, STRING, GeneMANIA, UCSC Xena, Enrichr, and OSluca databases. FAS expression was subsequently investigated at the protein level in samples from 578 lung cancer patients to understand its protein-level expression. In vitro validation of FAS gene expression was performed on H1299, H1993, A549 and HBE cell lines.ResultWe found that the expression of FAS was significantly downregulated in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) compared to normal lung tissue. In addition, we observed a higher level of FAS promoter methylation in LUSC tissue than in normal tissue. FAS alterations were rare (1.9%) in lung cancer samples, with deep deletions being more common than missense mutations, which occurred mainly in the TNFR-like cysteine-rich domain and the death domain. We also identified a list of proteins interacting with FAS and genes co-expressed with FAS, with LUAD having 11 co-expressed genes and LUSC having 90 co-expressed genes. Our results also showed that FAS expression has limited prognostic significance (HR=1.302, 95% CI=0.935-1.139, P=0.530). Protein level investigation revealed that FAS expression varied among individuals, with nTPM values ranging from 5.2 to 67.2.ConclusionThis study provides valuable insights into the involvements and characteristics of FAS in lung cancer. Further studies are needed to investigate the clinical significance of FAS alterations in lung cancer and to explore the potential of targeting FAS for therapeutic intervention.

Project description:Inhibition of glycolysis has been considered as a therapeutic approach in aggressive cancers including lung cancer. Abbreviated gluconeogenesis, mediated by phosphoenolpyruvate carboxykinase (PEPCK), was recently discovered to partially circumvent the need for glycolysis in lung cancer cells. However, the interplay of glycolysis and gluconeogenesis in lung cancer is still poorly understood. Here, we analyzed the expression of GLUT1, the prime glucose transporter, and of PCK1 and PCK2, the cytoplasmic and mitochondrial isoforms of PEPCK, in 450 samples of non-small cell lung cancer (NSCLC) and in 54 NSCLC metastases using tissue microarrays and whole tumor sections. Spatial distribution was assessed by automated image analysis. Additionally, glycolytic and gluconeogenic gene expression was inferred from The Cancer Genome Atlas (TCGA) datasets. We found that PCK2 was preferentially expressed in the lung adenocarcinoma subtype, while GLUT1 expression was higher in squamous cell carcinoma. GLUT1 and PCK2 were inversely correlated, GLUT1 showing elevated expression in larger tumors while PCK2 was highest in smaller tumors. However, a mixed phenotype showing the presence of both, glycolytic and gluconeogenic cancer cells was frequent. In lung adenocarcinoma, PCK2 expression was associated with significantly improved overall survival, while the opposite was found for GLUT1. The metabolic tumor microenvironment and the 3-dimensional context play an important role in modulating both pathways, since PCK2 expression preferentially occurred at the tumor margin and hypoxia regulated both, glycolysis and gluconeogenesis, in NSCLC cells in vitro, albeit in opposite directions. PCK1/2 expression was enhanced in metastases compared to primary tumors, possibly related to the different environment. The results of this study show that glycolysis and gluconeogenesis are activated in NSCLC in a tumor size and oxygenation modulated manner and differentially correlate with outcome. The frequent co-activation of gluconeogenesis and glycolysis in NSCLC should be considered in potential future therapeutic strategies targeting cancer cell metabolism.

Dataset Information

Prognostic significance of KRT19 in Lung Squamous Cancer.

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Prognostic significance of KRT19 in Lung Squamous Cancer.

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