Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma

Abstract Background Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). Aquaporin 9 (AQP9) is involved in many immune-related signals; however, its role in ccRCC remains to be elucidated. This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. Methods A total of 913 ccRCC patients with available RNA-sequence data from the Cancer Genome Atlas (TCGA) database and Fudan University Shanghai Cancer Center (FUSCC) were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained and validated using multiple datasets. A partial likelihood test from Cox regression analysis was developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method and log-rank test were performed to assess survival. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of AQP9 using area under the curve (AUC) score. Functional enrichment analyses and immune infiltration analysis were used to describe significantly involved hallmark pathways of hub genes. Results Significantly elevated transcriptional and proteomic AQP9 expressions were found in ccRCC samples. Increased AQP9 mRNA expression was significantly associated with advanced clinicopathological parameters and correlated with shorter PFS and OS in TCGA and FUSCC cohorts (p < 0.001). ROC curves suggested the significant diagnostic and prognostic ability of AQP9 (PFS, AUC = 0.823; OS, AUC = 0.828). Functional annotations indicated that AQP9 is involved in the most significant hallmarks including complement, coagulation, IL6/JAK–STAT3, inflammatory response and TNF-alpha signaling pathways. Conclusion Our study revealed that elevated AQP9 expression was significantly correlated with aggressive progression, poor survival and immune infiltrations in ccRCC patients, and we validated its prognostic value in a real-world cohort. These data suggest that AQP9 may act as an oncogene and a promising prognostic marker in ccRCC.

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Data Mining of Prognostic Microenvironment-Related Genes in Clear Cell Renal Cell Carcinoma: A Study with TCGA Database

Disease Markers ◽

10.1155/2019/8901649 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Bin Chen ◽

Wei Chen ◽

Jing Jin ◽

Xueping Wang ◽

Yifang Cao ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Value ◽

Clear Cell ◽

Enrichment Analysis ◽

Cancer Prognosis ◽

Functional Enrichment ◽

Ppi Network ◽

Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent kidney malignancies. The tumor microenvironment (TME) is highly related to the oncogenesis, progress, and prognosis of ccRCC. The aim of this study was to infer the level of infiltrating stromal and immune cells and assess the prognostic value of them. The gene expression profile was obtained from TCGA and used for calculating the stromal and immune scores. Based on a cut-off value, patients were divided into low- and high-stromal/immune score groups. Survival analysis was performed to evaluate the prognostic value of stromal and immune scores. Moreover, differentially expressed genes (DEGs) that are highly related to TME were determined and applied for functional enrichment analysis and protein-protein interaction (PPI) network. The Kaplan-Meier plot demonstrated that patients with high-immune scores and stromal scores had poorer clinical outcome. In addition, a total of 89 DEGs were identified and mainly involved in 5 pathways. The top 5 degree genes were extracted from the PPI network; among them, IL10 and XCR1 were highly associated with prognosis of ccRCC. The results of the present study demonstrated that ESTIMATE algorithm-based stromal and immune scores may be a credible indicator of cancer prognosis and IL10 along with XCR1 may be a potential key regulator for the TME of ccRCC.

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Prognostic value of epithelial-mesenchymal transition markers in clear cell renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.739 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 739-739

Author(s):

Yuan-Yuan Qu ◽

Xi Tian ◽

Wenhao Xu ◽

Aihemutaijiang Anwaier ◽

Dingwei Ye ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Value ◽

Clear Cell ◽

Functional Enrichment ◽

Cell Renal Cell Carcinoma ◽

Mesenchymal Transition ◽

Epithelial Marker ◽

Emt Markers

739 Background: Epithelial-to-mesenchymal transition (EMT) in important in tumor invasiveness and metastasis. We aimed to determine prognostic value of six key EMT markers (CDH1, CDH2, SNAI1, SNAI2, VIM, TWIST1) in clear cell renal cell carcinoma (ccRCC). Methods: A total of 533 ccRCC patients with RNASeq data from The Cancer Genome Atlas (TCGA) cohort were included for analysis. Gene expression of these EMT markers was compared between tumor and normal tissues based on Oncomine database and TCGA cohort. Their correlations with progression-free survival (PFS) and overall survival (OS) were also examined in both TCGA cohort and FUSCC (Fudan University Shanghai Cancer Center) cohort. Cox proportional hazards regression model and Kaplan-Meier plot were used to assess the relative factors. Functional enrichment analyses were utilized to describe biologic function annotations and significantly involved hallmarks pathways of each gene. Results: We found that Epithelial marker, CDH1 expression was lower, while mesenchymal markers (CDH2, SNAI1, VIM, TWIST1) expression was higher in ccRCC primary tumors. In the TCGA cohort, we found that patients with higher expression of VIM, TWIST1 or lower expression of CDH1 had worse prognosis. Further, in the FUSCC cohort, we confirmed the predictive ability of mesenchymal markers and epithelial marker expression in PFS and OS of ccRCC patients. After generating Cox regression models, EMT markers (CDH1, SNAI1, VIM, and TWIST1) were independent prognostic factors of both PFS and OS in ccRCC patients. Conclusions: Our preliminary EMT prediction model can facilitate further screening of EMT biomarkers and cast a better understanding of EMT gene function in ccRCC.

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Identification for prognostic value of differentially expressed genes in immune microenvironment of clear cell renal cell carcinoma

10.21203/rs.2.16420/v1 ◽

2019 ◽

Author(s):

Xingming Zhang ◽

Xiaoxue Yin ◽

Zhenhua Liu ◽

Guangxi Sun ◽

Xudong Zhu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

T Cells ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Functional Enrichment ◽

Clinicopathological Parameters ◽

Resting Cells ◽

Immune Microenvironment ◽

Cell Renal Cell Carcinoma

Abstract Background: Genes related to Anchorimmune microenvironment of clear cell renal cell carcinoma (ccRCC) remains unclear. We aimed to identify related to immune microenvironment and to screen the most significant genes to predict outcomes of ccRCC. Methods: Gene expression and clinicopathological data from TCGA data portal were obtained (KIRC). Immune and stromal scores were calculated based on ESTIMATE algorithm. DEGs between low and high groups of immune scores were identified. Subsequent functional enrichment analysis and protein-protein interaction of DEGs were conducted by DAVID database. Results: Patients were divided into low and high groups by medians according to immune (median: 1038.45) and stromal scores (median: 667.945), respectively. Immune scores were significantly correlated with clinicopathological parameters and overall survival (OS). Based on immune scores, 1433 genes were up-regulated, and among them, 890 DEGs were significantly associated with OS. Based on top 10 DEGs, cases with number of up-regulated genes ≥5 were associated poor OS (P = 0.002). In addition, the mean differences of percentages of CD8 T cells (11.32%), CD4 memory resting T cells (-4.52%) and mast resting cells (-3.55%) between low and high immune scores were the most significant. Conclusions: A list of immune microenvironment-related genes in ccRCC was initially identified, and high immune score was an independent poor prognostic factor of OS. Furthermore, the combination of these genes might use to predict the efficacy of immunotherapy. Further analyses of these genes were warrant to explore their potential association with the prognosis of ccRCC.

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