Abnormal expression and the significant prognostic value of aquaporins in clear cell renal cell carcinoma

Li, Mingrui; He, Minxin; Xu, Fangshi; Guan, Yawen; Tian, Jie; Wan, Ziyan; Zhou, Haibin; Gao, Mei; Chong, Tie

doi:10.1371/journal.pone.0264553

Cited by 11 publications

(8 citation statements)

References 76 publications

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“…The limitations of our study include its retrospective, single-institution design, and the small sample size. In addition, other putative patient statuses, such as diabetes mellitus, cardiovascular disease, and smoking [ 2 , 5 , 29 , 30 ], which have been shown to be prognostic factors for RCC patients, were not examined in the current study. Larger prospective randomized controlled trials are needed to confirm our preliminary findings.…”

Section: Discussionmentioning

confidence: 99%

Elevated Plasma Interleukin-35 as a Prognostic Indicator in Localized Clear Cell Renal Cell Carcinoma

Zhang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Purpose. The aim of the study is to investigate the prognostic value of plasma interleukin-35 in the surgical treatment of patients with clear cell renal cell carcinoma (ccRCC). Material and Methods. Plasma IL-35 levels were measured in patients with ccRCC. The cut-off value of IL-35 was determined by the receiver operating characteristic (ROC) analysis and the area under the curve (AUC). The effects of the IL-35 and other clinicopathological characteristics on overall survival (OS) and progression-free survival (PFS) were evaluated using the univariate and multivariate logistic regression analysis. Result. Sixty-four ccRCC patients admitted to the urology department at the First Affiliated Hospital of Soochow University were selected, of whom 50 were diagnosed with localized ccRCC. Plasma interleukin-35 levels were significantly higher in patients with ccRCC than that in healthy controls. The cut-off value of IL-35 was 99.7 pg/mL. Multivariate analysis selected by univariate analyses demonstrated that the preoperative IL-35 was an independent prognostic factor for 5-year OS (OR: 1.02, 95% CI: 1.01 to 1.04, p < 0.0001 ) and 5-year PFS (OR: 1.02, 95% CI: 1.00 to 1.03, p = 0.011 ) in all patients with localized ccRCC. Conclusion. Current results indicate that preoperative IL-35 is an independent prognostic marker for OS and RFS in patients with localized ccRCC after surgery.

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Section: Discussionmentioning

confidence: 99%

Elevated Plasma Interleukin-35 as a Prognostic Indicator in Localized Clear Cell Renal Cell Carcinoma

Zhang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…What's more, high AQP0/8/9 expression was significantly associated with poor OS. On the contrary, high levels of AQP1/2/3/4/5/6/7/10/11, particularly high levels of AQP1/4/7, were associated with better OS in ccRCC (23). KCNJ1, as a potassium inward rectifier channel, plays a significant role in potassium homeostasis by transporting potassium out of cells.…”

Section: Discussionmentioning

confidence: 98%

Screening of possible biomarkers and therapeutic targets in kidney renal clear cell carcinoma: Evidence from bioinformatic analysis

et al. 2022

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Renal cell carcinoma (RCC), as one of the most common urological malignancies, has many histologic and molecular subtypes, among which clear cell renal cell carcinoma (ccRCC) is one of the most common causes of tumor-related deaths. However, the molecular mechanism of ccRCC remains unclear. In order to identify the candidate genes that may exist in the occurrence and development of ccRCC, microarray datasets GSE6344, GSE16441, GSE36895, GSE53757 and GSE76351 had been downloaded from Gene Expression Omnibus (GEO) database. Apart from that, the differentially expressed genes (DEGs) were screened through Bioinformatics & Evolutionary Genomics. In addition, the protein-protein interaction network (PPI) was constructed, and the module analysis was performed using STRING and Cytoscape. By virtue of DAVID online database, GO/KEGG enrichment analysis of DEGs was performed. Consequently, a total of 118 DEGs were screened, including 24 up-regulated genes and 94 down-regulated genes. The plug-in MCODE of Cytoscape was adopted to analyze the most significant modules of DEGs. What’s more, the genes with degree greater than 10 in DEGs were selected as the hub genes. The overall survival (OS) and disease progression free survival (DFS) of 9 hub genes were analyzed through GEPIA2 online platform. As shown by the survival analysis, SLC34A1, SLC12A3, SLC12A1, PLG, and ENO2 were closely related to the OS of ccRCC, whereas SLC34A1 and LOX were closely related to DFS. Among 11 SLC members, 6 SLC members were highly expressed in non-cancerous tissues (SLC5A2, SLC12A1, SLC12A3, SLC34A1, SLC34A2, SLC34A3). Besides, SLC12A5 and SLC12A7 were highly expressed in ccRCC. Furthermore, SLC12A1-A7, SLC34A1 and SLC34A3 were closely related to OS, whereas SLC12A2/A4/A6/A7 and SLC34A1/A3 were closely related to DFS. In addition, 5 algorithms were used to analyze hub genes, the overlapping genes were AQP2 and KCNJ1. To sum up, hub gene can help us understand the molecular mechanism of the occurrence and development of ccRCC, thereby providing a theoretical basis for the diagnosis and targeted therapy of ccRCC.

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“…In this context, it has been reported that the correlation between transcription and protein expression may not always be absolute in eukaryotic genes ( de Sousa Abreu et al, 2009 ; Maier et al, 2009 ; Vogel and Marcotte, 2012 ), including aquaporins ( Prat et al, 2012 ; Bednar et al, 2015 ; Yepes-Molina et al, 2020 ). Nonetheless, in case of mammalian aquaporins, such disconnect between mRNA and protein levels has been reported to be dependent on the biological context ( Bednar et al, 2015 ; Li et al, 2022 ). For instance, AQPs 1, 2, 3, 4, 5, and 6 in human renal carcinoma versus normal renal tissues showed consistent trends between their protein levels and mRNA levels ( Li et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nonetheless, in case of mammalian aquaporins, such disconnect between mRNA and protein levels has been reported to be dependent on the biological context ( Bednar et al, 2015 ; Li et al, 2022 ). For instance, AQPs 1, 2, 3, 4, 5, and 6 in human renal carcinoma versus normal renal tissues showed consistent trends between their protein levels and mRNA levels ( Li et al, 2022 ). In comparison, AQPs in human placental amnion versus reflected amnion showed similar qualitative profiles but discordant quantitative relationship for some AQP isoforms ( Bednar et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Differential modulation of lung aquaporins among other pathophysiological markers in acute (Cl2 gas) and chronic (carbon nanoparticles, cigarette smoke) respiratory toxicity mouse models

Bhattacharya

Yadav

et al. 2022

Front. Physiol.

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Inhaled toxic chemicals and particulates are known to disrupt lung homeostasis causing pulmonary toxicity and tissue injury. However, biomarkers of such exposures and their underlying mechanisms are poorly understood, especially for emerging toxicants such as engineered nanoparticles and chemical threat agents such as chlorine gas (Cl2). Aquaporins (AQPs), commonly referred to as water channels, are known to play roles in lung homeostasis and pathophysiology. However, little is known on their regulation in toxicant-induced lung injuries. Here, we compared four lung toxicity models namely, acute chemical exposure (Cl2)-, chronic particulate exposure (carbon nanotubes/CNT)-, chronic chemical exposure (cigarette smoke extract/CSE)-, and a chronic co-exposure (CNT + CSE)- model, for modulation of lung aquaporins (AQPs 1, 3, 4, and 5) in relation to other pathophysiological endpoints. These included markers of compromised state of lung mucosal lining [mucin 5b (MUC5B) and surfactant protein A (SP-A)] and lung-blood barrier [protein content in bronchoalveolar lavage (BAL) fluid and, cell tight junction proteins occludin and zona-occludens]. The results showed toxicity model-specific regulation of AQPs measured in terms of mRNA abundance. A differential upregulation was observed for AQP1 in acute Cl2 exposure model (14.71-fold; p = 0.002) and AQP3 in chronic CNT exposure model (3.83-fold; p = 0.044). In contrast, AQP4 was downregulated in chronic CSE model whereas AQP5 showed no significant change in any of the models. SP-A and MUC5B expression showed a decreasing pattern across all toxicity models except the acute Cl2 toxicity model, which showed a highly significant upregulation of MUC5B (25.95-fold; p = 0.003). This was consistent with other significant pathophysiological changes observed in this acute model, particularly a compromised lung epithelial-endothelial barrier indicated by significantly increased protein infiltration and expression of tight junction proteins, and more severe histopathological (structural and immunological) changes. To our knowledge, this is the first report on lung AQPs as molecular targets of the study toxicants. The differentially regulated AQPs, AQP1 in acute Cl2 exposure versus AQP3 in chronic CNT nanoparticle exposure, in conjunction with the corresponding differentially impacted pathophysiological endpoints (particularly MUC5B) could potentially serve as predictive markers of toxicant type-specific pulmonary injury and as candidates for future investigation for clinical intervention.

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Abnormal expression and the significant prognostic value of aquaporins in clear cell renal cell carcinoma

Cited by 11 publications

References 76 publications

Elevated Plasma Interleukin-35 as a Prognostic Indicator in Localized Clear Cell Renal Cell Carcinoma

Elevated Plasma Interleukin-35 as a Prognostic Indicator in Localized Clear Cell Renal Cell Carcinoma

Screening of possible biomarkers and therapeutic targets in kidney renal clear cell carcinoma: Evidence from bioinformatic analysis

Differential modulation of lung aquaporins among other pathophysiological markers in acute (Cl2 gas) and chronic (carbon nanoparticles, cigarette smoke) respiratory toxicity mouse models

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