Abstract
BackgroundGrowing 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.MethodsA 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.ResultsSignificantly 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.ConclusionOur 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.
Highlights
Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma
We examined the prognostic value of the expressions of the AQP family members in clear cell renal cell carcinoma (ccRCC) and found that patients with high Aquaporin 9 (AQP9) expression had poor survival
We assessed differential AQP9 expression at the transcriptional and protein level according to datasets hosted on the Oncomine, the Cancer Genome Atlas (TCGA) and Fudan University Shanghai Cancer Center (FUSCC) platforms
Summary
Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. Accumulating studies have shown that AQPs regulate rapid water movement in various epithelial and non-epithelial tissues [9, 10], and participate in the pathological process of several diseases such as glaucoma, cancer, inflammation, immunity, and obesity [11]. Several AQPs are over-expressed in tumors samples and serve notable roles in cancer progression [12]. A previous study showed that AQP1 was a unique non-invasive biomarker for screening and diagnosing malignant clear cells or papillary RCC [13]. Chen et al found that AQP3 promoted prostate cancer cell invasion through extracellular signal-regulated kinase 1/2-mediated MMP-3 secretion [14]. Understanding of the regulation and molecular function of AQP9 may identify potential targets for the diagnosis and treatment of ccRCC
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