AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment

BackgroundIt is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear.Methods and ResultsUsing the CIBERSORT and ESTIMATE calculation methods, t...

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Autores principales: Jibo Jing, Jin Sun, Yuqing Wu, Nieke Zhang, Chunhui Liu, Saisai Chen, Wenchao Li, Cheng Hong, Bin Xu, Ming Chen
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:25ffcb8a6b2544099ae7bf0ffc44e1652021-11-05T11:40:46ZAQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment2234-943X10.3389/fonc.2021.770565https://doaj.org/article/25ffcb8a6b2544099ae7bf0ffc44e1652021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.770565/fullhttps://doaj.org/toc/2234-943XBackgroundIt is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear.Methods and ResultsUsing the CIBERSORT and ESTIMATE calculation methods, the scores of the two main fractions of tumor-infiltrating immune cells (TICs) from The Cancer Genome Atlas (TCGA) database of 537 KIRC patients were calculated. Subsequently, differentially expressed genes (DEGs) were drawn out by performing an overlap between Cox regression analysis and protein–protein interaction (PPI) network. Aquaporin 9 (AQP9) was identified as a latent predictor through the process. Following research revealed that AQP9 expression was positively correlated with the pathological characteristics (TNM stage) and negatively connected with survival time. Then, by performing gene set enrichment analysis (GSEA), it can be inferred that genes with high expression level of AQP9 were mainly enriched in immune-related activities, while low AQP9 group was associated with functions of cellular metabolism. Further studies have shown that regulatory T cells (Tregs), macrophages M2, macrophages M0, CD4+ T cells, and neutrophils were positively correlated with AQP9 expression. While the levels of mast cells, natural killer (NK) cells, and CD8+ T cells are negatively correlated with AQP9. The result of multiple immunohistochemistry (mIHC) suggests a negative relevance between AQP9 and CD8+ T cells and reveals a trend of consistent change on AQP9 and M2 macrophages.ConclusionThe expression level of AQP9 may be helpful in predicting the prognosis of patients with KIRC, especially to the TME state transition, the mechanism of which is possibly through lipid metabolism and P53, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways that affect M2 polarization. AQP9 was associated with the expression levels of M2, tumor-associated macrophages (TAMs), and the recruitment of CD8+ T cells in tumor environment. The research result indicates that AQP9 may be an obstacle to maintain the immune activity of TME.Jibo JingJibo JingJibo JingJin SunYuqing WuYuqing WuYuqing WuNieke ZhangNieke ZhangNieke ZhangChunhui LiuChunhui LiuChunhui LiuSaisai ChenSaisai ChenSaisai ChenWenchao LiWenchao LiWenchao LiCheng HongCheng HongCheng HongBin XuBin XuBin XuMing ChenMing ChenMing ChenFrontiers Media S.A.articletumor microenvironmentalrenal clear cell carcinoma (KIRC)TCGAextracellular matrix (ECM)tumor-associated macrophages (TAMs)AQP9Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic tumor microenvironmental
renal clear cell carcinoma (KIRC)
TCGA
extracellular matrix (ECM)
tumor-associated macrophages (TAMs)
AQP9
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle tumor microenvironmental
renal clear cell carcinoma (KIRC)
TCGA
extracellular matrix (ECM)
tumor-associated macrophages (TAMs)
AQP9
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Jibo Jing
Jibo Jing
Jibo Jing
Jin Sun
Yuqing Wu
Yuqing Wu
Yuqing Wu
Nieke Zhang
Nieke Zhang
Nieke Zhang
Chunhui Liu
Chunhui Liu
Chunhui Liu
Saisai Chen
Saisai Chen
Saisai Chen
Wenchao Li
Wenchao Li
Wenchao Li
Cheng Hong
Cheng Hong
Cheng Hong
Bin Xu
Bin Xu
Bin Xu
Ming Chen
Ming Chen
Ming Chen
AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment
description BackgroundIt is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear.Methods and ResultsUsing the CIBERSORT and ESTIMATE calculation methods, the scores of the two main fractions of tumor-infiltrating immune cells (TICs) from The Cancer Genome Atlas (TCGA) database of 537 KIRC patients were calculated. Subsequently, differentially expressed genes (DEGs) were drawn out by performing an overlap between Cox regression analysis and protein–protein interaction (PPI) network. Aquaporin 9 (AQP9) was identified as a latent predictor through the process. Following research revealed that AQP9 expression was positively correlated with the pathological characteristics (TNM stage) and negatively connected with survival time. Then, by performing gene set enrichment analysis (GSEA), it can be inferred that genes with high expression level of AQP9 were mainly enriched in immune-related activities, while low AQP9 group was associated with functions of cellular metabolism. Further studies have shown that regulatory T cells (Tregs), macrophages M2, macrophages M0, CD4+ T cells, and neutrophils were positively correlated with AQP9 expression. While the levels of mast cells, natural killer (NK) cells, and CD8+ T cells are negatively correlated with AQP9. The result of multiple immunohistochemistry (mIHC) suggests a negative relevance between AQP9 and CD8+ T cells and reveals a trend of consistent change on AQP9 and M2 macrophages.ConclusionThe expression level of AQP9 may be helpful in predicting the prognosis of patients with KIRC, especially to the TME state transition, the mechanism of which is possibly through lipid metabolism and P53, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways that affect M2 polarization. AQP9 was associated with the expression levels of M2, tumor-associated macrophages (TAMs), and the recruitment of CD8+ T cells in tumor environment. The research result indicates that AQP9 may be an obstacle to maintain the immune activity of TME.
format article
author Jibo Jing
Jibo Jing
Jibo Jing
Jin Sun
Yuqing Wu
Yuqing Wu
Yuqing Wu
Nieke Zhang
Nieke Zhang
Nieke Zhang
Chunhui Liu
Chunhui Liu
Chunhui Liu
Saisai Chen
Saisai Chen
Saisai Chen
Wenchao Li
Wenchao Li
Wenchao Li
Cheng Hong
Cheng Hong
Cheng Hong
Bin Xu
Bin Xu
Bin Xu
Ming Chen
Ming Chen
Ming Chen
author_facet Jibo Jing
Jibo Jing
Jibo Jing
Jin Sun
Yuqing Wu
Yuqing Wu
Yuqing Wu
Nieke Zhang
Nieke Zhang
Nieke Zhang
Chunhui Liu
Chunhui Liu
Chunhui Liu
Saisai Chen
Saisai Chen
Saisai Chen
Wenchao Li
Wenchao Li
Wenchao Li
Cheng Hong
Cheng Hong
Cheng Hong
Bin Xu
Bin Xu
Bin Xu
Ming Chen
Ming Chen
Ming Chen
author_sort Jibo Jing
title AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment
title_short AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment
title_full AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment
title_fullStr AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment
title_full_unstemmed AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment
title_sort aqp9 is a prognostic factor for kidney cancer and a promising indicator for m2 tam polarization and cd8+ t-cell recruitment
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/25ffcb8a6b2544099ae7bf0ffc44e165
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