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Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma
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 inv...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842264/ https://www.ncbi.nlm.nih.gov/pubmed/31703694 http://dx.doi.org/10.1186/s12967-019-2113-y |
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author | Xu, Wen-Hao Shi, Shen-Nan Xu, Yue Wang, Jun Wang, Hong-Kai Cao, Da-Long Shi, Guo-Hai Qu, Yuan-Yuan Zhang, Hai-Liang Ye, Ding-Wei |
author_facet | Xu, Wen-Hao Shi, Shen-Nan Xu, Yue Wang, Jun Wang, Hong-Kai Cao, Da-Long Shi, Guo-Hai Qu, Yuan-Yuan Zhang, Hai-Liang Ye, Ding-Wei |
author_sort | Xu, Wen-Hao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6842264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68422642019-11-14 Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma Xu, Wen-Hao Shi, Shen-Nan Xu, Yue Wang, Jun Wang, Hong-Kai Cao, Da-Long Shi, Guo-Hai Qu, Yuan-Yuan Zhang, Hai-Liang Ye, Ding-Wei J Transl Med Research 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. BioMed Central 2019-11-08 /pmc/articles/PMC6842264/ /pubmed/31703694 http://dx.doi.org/10.1186/s12967-019-2113-y Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Xu, Wen-Hao Shi, Shen-Nan Xu, Yue Wang, Jun Wang, Hong-Kai Cao, Da-Long Shi, Guo-Hai Qu, Yuan-Yuan Zhang, Hai-Liang Ye, Ding-Wei Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma |
title | Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma |
title_full | Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma |
title_fullStr | Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma |
title_full_unstemmed | Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma |
title_short | Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma |
title_sort | prognostic implications of aquaporin 9 expression in clear cell renal cell carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842264/ https://www.ncbi.nlm.nih.gov/pubmed/31703694 http://dx.doi.org/10.1186/s12967-019-2113-y |
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