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Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a malignant renal tumor that is highly prone to metastasis and recurrence. The exact pathogenesis of this cancer is still not well understood. This study aimed to identify novel hub genes in renal clear cell carcinoma and determine their diagnost...

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Autores principales: Qiu, Jiechuan, Wang, Zicheng, Xu, Yingkun, Zhao, Leizuo, Zhang, Peizhi, Gao, Han, Wang, Qingliang, Xia, Qinghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044763/
https://www.ncbi.nlm.nih.gov/pubmed/36978048
http://dx.doi.org/10.1186/s12894-023-01212-x
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author Qiu, Jiechuan
Wang, Zicheng
Xu, Yingkun
Zhao, Leizuo
Zhang, Peizhi
Gao, Han
Wang, Qingliang
Xia, Qinghua
author_facet Qiu, Jiechuan
Wang, Zicheng
Xu, Yingkun
Zhao, Leizuo
Zhang, Peizhi
Gao, Han
Wang, Qingliang
Xia, Qinghua
author_sort Qiu, Jiechuan
collection PubMed
description OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a malignant renal tumor that is highly prone to metastasis and recurrence. The exact pathogenesis of this cancer is still not well understood. This study aimed to identify novel hub genes in renal clear cell carcinoma and determine their diagnostic and prognostic value. METHODS: Intersection genes were obtained from multiple databases, and protein–protein interaction analysis and functional enrichment analysis were performed to identify key pathways related to the intersection genes. Hub genes were identified using the cytoHubba plugin in Cytoscape. GEPIA and UALCAN were utilized to observe differences in mRNA and protein expression of hub genes between KIRC and adjacent normal tissues. The Wilcoxon rank sum test was used to analyze hub gene levels between paired KIRC and matched non-cancer samples. IHC results were obtained from the HPA online database, and according to the median gene expression level, they were divided into a high-expression group and a low-expression group. The correlation of these groups with the prognosis of KIRC patients was analyzed. Logistic regression and the Wilcoxon rank sum test were used to test the relationship between SLC34A1 level and clinicopathological features. The diagnostic value of SLC34A1 was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Cox regression analysis was used to analyze the relationship between clinicopathological features, SLC34A1 expression, and KIRC survival rate. LinkedOmics was used to obtain the genes most related to SLC34A1 and their functional enrichment. Genetic mutations and methylation levels of SLC34A1 in KIRC were obtained from the cBioPortal website and the MethSurv website, respectively. RESULTS: Fifty-eight ccRCC differential genes were identified from six datasets, and they were mainly enriched in 10 functional items and 4 pathways. A total of 5 hub genes were identified. According to the GEPIA database analysis, low expression of SLC34A1, CASR, and ALDOB in tumors led to poor prognosis. Low expression of SLC34A1 mRNA was found to be related to clinicopathological features of patients. SLC34A1 expression in normal tissues could accurately identify tumors (AUC 0.776). SLC34A1 was also found to be an independent predictor of ccRCC in univariate and multivariate Cox analyses. The mutation rate of the SLC34A1 gene was 13%. Eight of the 10 DNA methylated CpG sites were associated with the prognosis of ccRCC. SLC34A1 expression in ccRCC was positively correlated with B cells, eosinophils, neutrophils, T cells, TFH, and Th17 cells, and negatively correlated with Tem, Tgd, and Th2 cells. CONCLUSION: The expression level of SLC34A1 in KIRC samples was found to be decreased, which predicted a decreased survival rate of KIRC. SLC34A1 may serve as a molecular prognostic marker and therapeutic target for KIRC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-023-01212-x.
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spelling pubmed-100447632023-03-29 Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma Qiu, Jiechuan Wang, Zicheng Xu, Yingkun Zhao, Leizuo Zhang, Peizhi Gao, Han Wang, Qingliang Xia, Qinghua BMC Urol Research OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a malignant renal tumor that is highly prone to metastasis and recurrence. The exact pathogenesis of this cancer is still not well understood. This study aimed to identify novel hub genes in renal clear cell carcinoma and determine their diagnostic and prognostic value. METHODS: Intersection genes were obtained from multiple databases, and protein–protein interaction analysis and functional enrichment analysis were performed to identify key pathways related to the intersection genes. Hub genes were identified using the cytoHubba plugin in Cytoscape. GEPIA and UALCAN were utilized to observe differences in mRNA and protein expression of hub genes between KIRC and adjacent normal tissues. The Wilcoxon rank sum test was used to analyze hub gene levels between paired KIRC and matched non-cancer samples. IHC results were obtained from the HPA online database, and according to the median gene expression level, they were divided into a high-expression group and a low-expression group. The correlation of these groups with the prognosis of KIRC patients was analyzed. Logistic regression and the Wilcoxon rank sum test were used to test the relationship between SLC34A1 level and clinicopathological features. The diagnostic value of SLC34A1 was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Cox regression analysis was used to analyze the relationship between clinicopathological features, SLC34A1 expression, and KIRC survival rate. LinkedOmics was used to obtain the genes most related to SLC34A1 and their functional enrichment. Genetic mutations and methylation levels of SLC34A1 in KIRC were obtained from the cBioPortal website and the MethSurv website, respectively. RESULTS: Fifty-eight ccRCC differential genes were identified from six datasets, and they were mainly enriched in 10 functional items and 4 pathways. A total of 5 hub genes were identified. According to the GEPIA database analysis, low expression of SLC34A1, CASR, and ALDOB in tumors led to poor prognosis. Low expression of SLC34A1 mRNA was found to be related to clinicopathological features of patients. SLC34A1 expression in normal tissues could accurately identify tumors (AUC 0.776). SLC34A1 was also found to be an independent predictor of ccRCC in univariate and multivariate Cox analyses. The mutation rate of the SLC34A1 gene was 13%. Eight of the 10 DNA methylated CpG sites were associated with the prognosis of ccRCC. SLC34A1 expression in ccRCC was positively correlated with B cells, eosinophils, neutrophils, T cells, TFH, and Th17 cells, and negatively correlated with Tem, Tgd, and Th2 cells. CONCLUSION: The expression level of SLC34A1 in KIRC samples was found to be decreased, which predicted a decreased survival rate of KIRC. SLC34A1 may serve as a molecular prognostic marker and therapeutic target for KIRC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12894-023-01212-x. BioMed Central 2023-03-28 /pmc/articles/PMC10044763/ /pubmed/36978048 http://dx.doi.org/10.1186/s12894-023-01212-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Qiu, Jiechuan
Wang, Zicheng
Xu, Yingkun
Zhao, Leizuo
Zhang, Peizhi
Gao, Han
Wang, Qingliang
Xia, Qinghua
Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma
title Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma
title_full Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma
title_fullStr Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma
title_full_unstemmed Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma
title_short Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma
title_sort low expression of slc34a1 is associated with poor prognosis in clear cell renal cell carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10044763/
https://www.ncbi.nlm.nih.gov/pubmed/36978048
http://dx.doi.org/10.1186/s12894-023-01212-x
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