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Reduced GRAMD1C expression correlates to poor prognosis and immune infiltrates in kidney renal clear cell carcinoma.

ABSTRACT: There has been an increase in the mortality rate and morbidity of kidney cancer (KC) with kidney renal clear cell carcinoma (KIRC) being the most common subtype of KC. GRAMD1C (GRAM Domain Containing 1C) has not been reported to relate to prognosis and immunotherapy in any cancers. Using bioinformatics methods, we judged the prognostic value of GRAMD1C expression in KIRC and investigated the underlying mechanisms of GRAMD1C affecting the overall survival of KIRC based on data downloaded from The Cancer Genome Atlas (TCGA). The outcome revealed that reduced GRAMD1C expression could be a promising predicting factor of poor prognosis in kidney renal clear cell carcinoma. Meanwhile, GRAMDIC expression was significantly correlated to several tumor-infiltrating immune cells (TIICs), particularly the regulatory T cells (Tregs). Furthermore, GRAMD1C was most significantly associated with the mTOR signaling pathway, RNA degradation, WNT signaling pathway, toll pathway and AKT pathway in KIRC. Thus, GRAMD1C has the potential to become a novel predictor to evaluate prognosis and immune infiltration for KIRC patients.

SUBMITTER: Hao H

PROVIDER: S-EPMC6927341 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Reduced GRAMD1C expression correlates to poor prognosis and immune infiltrates in kidney renal clear cell carcinoma.

Hao Haiyan H Wang Ziheng Z Ren Shiqi S Shen Hanyu H Xian Hua H Ge Wenliang W Wang Wei W

PeerJ 20191220

There has been an increase in the mortality rate and morbidity of kidney cancer (KC) with kidney renal clear cell carcinoma (KIRC) being the most common subtype of KC. GRAMD1C (GRAM Domain Containing 1C) has not been reported to relate to prognosis and immunotherapy in any cancers. Using bioinformatics methods, we judged the prognostic value of GRAMD1C expression in KIRC and investigated the underlying mechanisms of GRAMD1C affecting the overall survival of KIRC based on data downloaded from The ...[more]

PMID: 31875150

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Project description:Background: Petite Integration Factor 1 (PIF1) is a multifunctional helicase and DNA processing enzyme that plays an important role in the process of several cancer types. However, the relationship between clear cell renal cell carcinoma (ccRCC) and PIF1 remains unclear. This study aims to explore the role of PIF1 in ccRCC tumorigenesis and prognosis. Methods: Based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, we retrieved and verified the expression of PIF1 in ccRCC tissues as well as normal tissues. To assess the protein expression of PIF1 by using the Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). We also performed receiver operating characteristic (ROC) curve analysis to differentiate the effectiveness of PIF1 in ccRCC and adjacent normal tissues. To evaluate the value of PIF1 on clinical outcomes in ccRCC patients by using multivariate methods and Kaplan‒Meier survival curves. Protein‒protein interaction (PPI) networks were made with STRING. We determined the relationship between the expression of PIF1 and immune cell infiltration with single-sample gene set enrichment analysis (ssGSEA). Results: Compared with normal tissues, the expression of PIF1 was significantly elevated in ccRCC. The mRNA expression of PIF1 is correlated with high TNM stage and high pathologic stage. The receiver operating characteristic (ROC) curve analysis showed that PIF1 was related to an area under the curve (AUC) value of 0.928 to distinguish between ccRCC tissues and normal tissues. Kaplan‒Meier survival analysis showed that the overall survival (OS) of ccRCC patients with a high level of PIF1 was significantly shorter than that of those with a low level of PIF1. PIF1 may play an important role in the occurrence of tumors. Correlation analysis showed that PIF1-mediated carcinogenesis may participate in the process of tumor immune escape in ccRCC. Conclusion: PIF1 could be a reference biomarker to identify ccRCC patients with poor prognosis. PIF1 may play a distinct role in the microenvironment of ccRCC by regulating tumor infiltration of immune cells, which is a new therapeutic target to affect the growth of the tumor.

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Dataset Information

Reduced GRAMD1C expression correlates to poor prognosis and immune infiltrates in kidney renal clear cell carcinoma.

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Reduced GRAMD1C expression correlates to poor prognosis and immune infiltrates in kidney renal clear cell carcinoma.

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