Dataset Information

Comprehensive analysis of gene regulation network and immune signatures of prognostic biomarker YAP1 in pancreatic cancer.

ABSTRACT: Background: Pancreatic cancer (PC) is one of the most common digestive malignancy, with severe cancer-related death and disease burden. Yes-associated protein 1 (YAP1) has been reported to be involved in the tumorigenesis and progression of several cancers, thus leading to poor prognosis of patients. However, the relationship between YAP1 and immune microenvironment in PC deserve more scrutiny. Methods: GEPIA, OncoLnc, PROGgeneV2 and HPA database were utilized to analyze the expression (transcriptome and protein levels) and overall survival of YAP1 in PC. Then, we evaluated the risk factors associated with overall survival based on public data from TCGA-PAAD via Cox regression. Besides, LinkedOmics was utilized to identify co-expression genes and the potential regulation network of YAP1. Furthermore, we explored the relationship between YAP1 and immune infiltration using CIBERSORT algorithm and GEPIA database. Results: The age, lymph node metastasis status and up-regulated YAP1 expression have been proved to be independent prognostic factors for poor prognosis. The functions of YAP1 and co-expression genes were mainly involved in the angiogenesis, immune response-regulating signaling pathway, regulation of actin cytoskeleton, NOD-like receptor signaling pathway and cytokine-cytokine receptor interaction. Specifically, increased YAP1 expression was significantly correlated with immune infiltrating levels of resting CD4+T cells. Conclusions: Our findings provide evidence of the immune regulatory role of YAP1 in PC and help elucidate the role of YAP1 in carcinogenesis as well.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7592007 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comprehensive analysis of gene regulation network and immune signatures of prognostic biomarker YAP1 in pancreatic cancer.

Yang Yuan Y Zheng Ya Y Liu Xin X Ji Rui R Chen Zhaofeng Z Guo Qinghong Q Wu Guozhi G Wang Yuping Y Zhou Yongning Y

Journal of Cancer 20201008 23

<b>Background:</b> Pancreatic cancer (PC) is one of the most common digestive malignancy, with severe cancer-related death and disease burden. Yes-associated protein 1 (YAP1) has been reported to be involved in the tumorigenesis and progression of several cancers, thus leading to poor prognosis of patients. However, the relationship between YAP1 and immune microenvironment in PC deserve more scrutiny. <b>Methods:</b> GEPIA, OncoLnc, PROGgeneV2 and HPA database were utilized to analyze the expres ...[more]

PMID: 33123286

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Project description:Background: Yes-associated protein 1 (YAP1) is the main downstream effector of the Hippo signaling pathway, which is involved in tumorigenesis. This study aimed to comprehensively understand the prognostic performances of YAP1 expression and its potential mechanism in pan-cancers by mining databases. Methods: The YAP1 expression was evaluated by the Oncomine database and GEPIA tool. The clinical significance of YAP1 expression was analyzed by the UALCAN, GEPIA, and DriverDBv3 database. Then, the co-expressed genes with YAP1 were screened by the LinkedOmics, and annotated by the Metascape and DAVID database. Additionally, by the MitoMiner 4.0 v tool, the YAP1 co-expressed genes were screened to obtain the YAP1-associated mitochondrial genes that were further enriched by DAVID and analyzed by MCODE for the hub genes. Results: YAP1 was differentially expressed in human cancers. Higher YAP1 expression was significantly associated with poorer overall survival and disease-free survival in adrenocortical carcinoma (ACC), brain Lower Grade Glioma (LGG), and pancreatic adenocarcinoma (PAAD). The LinkedOmics analysis revealed 923 co-expressed genes with YAP1 in adrenocortical carcinoma, LGG and PAAD. The 923 genes mainly participated in mitochondrial functions including mitochondrial gene expression and mitochondrial respiratory chain complex I assembly. Of the 923 genes, 112 mitochondrial genes were identified by MitoMiner 4.0 v and significantly enriched in oxidative phosphorylation. The MCODE analysis identified three hub genes including CHCHD1, IDH3G and NDUFAF5. Conclusion: Our findings showed that the YAP1 overexpression could be a biomarker for poor prognosis in ACC, LGG and PAAD. Specifically, the YAP1 co-expression genes were mainly involved in the regulation of mitochondrial function especially in oxidative phosphorylation. Thus, our findings provided evidence of the carcinogenesis of YAP1 in human cancers and new insights into the mechanisms underlying the role of YAP1 in mitochondrial dysregulation.

Project description:BackgroundPancreatic cancer is one of the most common malignant tumors of the digestive tract, and it has a poor prognosis. Traditional methods are not effective to accurately assess the prognosis of patients with pancreatic cancer. Immunotherapy is a new promising approach for the treatment of pancreatic cancer; however, some patients do not respond well to immunotherapy, which may be related to tumor microenvironment regulation. In this study, we use gene expression database to mine important immune genes and establish a prognostic prediction model for pancreatic cancer patients. We hope to provide a feasible method to evaluate the prognosis of pancreatic cancer and provide valuable targets for pancreatic cancer immunotherapy.ResultsWe used univariate COX proportional hazard regression analysis, the least absolute shrinkage and selection operator, and multivariate COX regression analysis to screen 8 genes related to prognosis from the 314 immune-related genes, and used them to construct a new clinical prediction model in the TCGA pancreatic cancer cohort. Subsequently, we evaluated the prognostic value of the model. The Kaplan-Meier cumulative curve showed that patients with low risk scores survived significantly longer than patients with high risk scores. The area under the ROC curve (AUC value) of the risk score was 0.755. The univariate COX analysis showed that the risk score was significantly related to overall survival (HR 1.406, 95% CI 1.237-1.598, P?<?0.001), and multivariate analysis showed that the risk score was an independent prognostic factor (HR 1.400, 95% CI 1.287-1.522, P?<?0.001). Correlation analysis found that immune genes are closely related to tumor immune microenvironment.ConclusionsBased on the TCGA-PAAD cohort, we identified immune-related markers with independent prognostic significance, validated, and analyzed their biological functions, to provide a feasible method for the prognosis of pancreatic cancer and provide potentially valuable targets for pancreatic cancer immunotherapy.

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Comprehensive analysis of gene regulation network and immune signatures of prognostic biomarker YAP1 in pancreatic cancer.

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Comprehensive analysis of gene regulation network and immune signatures of prognostic biomarker YAP1 in pancreatic cancer.

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