Abstract A23: Gene set enrichment analysis of renal cell carcinoma genome-wide association data identifies the JAK-STAT pathway mediating susceptibility

In recent years, genome-wide RNA expression analysis has become a routine tool that offers a great opportunity to study and understand the key role of genes that contribute to carcinogenesis. Various microarray platforms and statistical approaches can be used to identify genes that might serve as prognostic biomarkers and be developed as antitumor therapies in the future. Metastatic renal cell carcinoma (mRCC) is a serious, life-threatening disease, and there are few treatment options for patients. In this study, we performed one-color microarray gene expression (4×44K) analysis of the mRCC cell line Caki-1 and the healthy kidney cell line ASE-5063. A total of 1,921 genes were differentially expressed in the Caki-1 cell line (1,023 upregulated and 898 downregulated). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) approaches were used to analyze the differential-expression data. The objective of this research was to identify complex biological changes that occur during metastatic development using Caki-1 as a model mRCC cell line. Our data suggest that there are multiple deregulated pathways associated with metastatic clear cell renal cell carcinoma (mccRCC), including integrin-linked kinase (ILK) signaling, leukocyte extravasation signaling, IGF-I signaling, CXCR4 signaling, and phosphoinositol 3-kinase/AKT/mammalian target of rapamycin signaling. The IPA upstream analysis predicted top transcriptional regulators that are either activated or inhibited, such as estrogen receptors, TP53, KDM5B, SPDEF, and CDKN1A. The GSEA approach was used to further confirm enriched pathway data following IPA.

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Key pathways and genes controlling the development and progression of clear cell renal cell carcinoma (ccRCC) based on gene set enrichment analysis

International Urology and Nephrology ◽

10.1007/s11255-013-0511-2 ◽

2013 ◽

Vol 46 (3) ◽

pp. 539-553 ◽

Cited By ~ 10

Author(s):

Haipeng Huang ◽

Yanyan Tang ◽

Wenwu He ◽

Qi Huang ◽

Jianing Zhong ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Gene Set Enrichment ◽

Cell Renal Cell Carcinoma ◽

Gene Set ◽

Key Pathways

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Low ASH1L Expression as Potential Diagnostic and Prognostic Biomarker for Renal Cell Carcinoma

Journal of Clinical & Experimental Immunology ◽

10.33140/jcei.06.02.05 ◽

2021 ◽

Vol 6 (2) ◽

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Enrichment Analysis ◽

Prognostic Indicator ◽

Diagnostic Value ◽

Gene Set Enrichment Analysis ◽

Autoimmune Response ◽

Gene Set Enrichment ◽

Cox Analysis

As an important methyltransferase, ASH1L played main roles in cell differentiation, embryonic development and autoimmune response. It had been reported that its abnormal expression was closely related to the progression of some diseases. In the current study, we found that ASH1L was low expressed in renal cell carcinoma, and its low expression was positively correlated with tumor progression. Patients with low ASH1L expression had poor OS and RFS, and it had excellent clinical diagnostic value. Furthermore, lower ASH1L expression in dead than survival patients, and multivariate regression Cox analysis confirmed that low ASH1L expression was a predictor for poor prognosis of patients with renal cell carcinoma. Gene-set-enrichment-analysis showed that the DNA-repair, reactive-oxygen-species pathway and Myc-target V2 signaling were significantly enriched to the low ASH1L expression phenotype. Taking together, our findings demonstrated that the low ASH1L expression was likely to be useful as a promising prognostic indicator for renal cell carcinoma.

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Pyroptosis Regulators and Tumor Microenvironment Infiltration Characterization in Clear Cell Renal Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.774279 ◽

2022 ◽

Vol 11 ◽

Author(s):

Xi Zhang ◽

Xiyi Wei ◽

Yichun Wang ◽

Shuai Wang ◽

Chengjian Ji ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Gene Set Enrichment ◽

Cell Renal Cell Carcinoma ◽

Gene Set

BackgroundIt is well known that chronic inflammation can promote the occurrence and progression of cancer. As a type of proinflammatory death, pyroptosis can recast a suitable microenvironment to promote tumor growth. However, the potential role of pyroptosis in clear cell renal cell carcinoma (ccRCC) remains unclear.MethodsThe transcriptome expression profile and mutation profile data of ccRCC with clinical characteristics included in this study were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus clustering was used for clustering. Gene set enrichment analysis (GSEA) analysis were applied to evaluate the biological mechanisms. Single sample gene set enrichment analysis (ssGSEA) was applied for evaluating the proportion of various immune infiltrating cells. The ESTIMATE algorithm was involved to compute the immune microenvironment scores.ResultsAmong the 17 pyroptosis regulators, a total of 15 pyroptosis regulators were differential expressed between tumor and normal tissues, in which 12 of them emerged strong correlations with prognoses. According to the pyroptosis components, the ccRCC patients were divided into four pyroptosis subtypes with different clinical, molecular, and pathway characteristics. Compared with other clusters, cluster B showed the pyroptosis heat phenotype, while cluster D represented the pyroptosis cold phenotype with poor overall survival. In addition, we performed principal component analysis (PCA) on the differential genes between clusters to construct the pyroptosis index. Furthermore, the pyroptosis index was significantly correlated with survival in different tumor mutation statuses and different grades and stages. Besides, the expression of pyroptosis-related regulators was related to the infiltration of immune cells and the expression of immune checkpoints, among which AIM2 was considered as the most significant immune-related pyroptosis regulator. Ultimately, we found that AIM2 was related to the immune activation pathway and was significantly overexpressed in tumor tissues.ConclusionThis study revealed that pyroptosis regulators and pyroptosis index played an important role in the development and prognoses of ccRCC. Moreover, AIM2 can be used as a predictor of the response of immunotherapy. Assessing the pyroptosis patterns may help evaluate the tumor status and guide immunotherapy strategies.

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