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

作者全名："Qiu, Jiechuan; Wang, Zicheng; Xu, Yingkun; Zhao, Leizuo; Zhang, Peizhi; Gao, Han; Wang, Qingliang; Xia, Qinghua"

作者地址："[Qiu, Jiechuan; Wang, Zicheng; Gao, Han; Wang, Qingliang; Xia, Qinghua] Shandong First Med Univ, Dept Urol, Shandong Prov Hosp, 9677 Jingshidong Rd, Jinan 250001, Shandong Provin, Peoples R China; [Xu, Yingkun] Chongqing Med Univ, Dept Breast & Thyroid Surg, Affiliated Hosp 1, Chongqing 400042, Peoples R China; [Zhao, Leizuo; Zhang, Peizhi; Xia, Qinghua] Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Urol, Jinan 250021, Peoples R China; [Zhao, Leizuo] Dongying Peoples Hosp, Dept Urol, Dongying 257000, Peoples R China"

通信作者："Xia, QH (通讯作者)，Shandong First Med Univ, Dept Urol, Shandong Prov Hosp, 9677 Jingshidong Rd, Jinan 250001, Shandong Provin, Peoples R China.; Xia, QH (通讯作者)，Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Urol, Jinan 250021, Peoples R China."

来源：BMC UROLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000962476600001

JCR分区：Q3

影响因子：1.7

年份：2023

卷号：23

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Clear cell renal cell carcinoma; Diagnosis; Prognostic marker

摘要："ObjectiveClear 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.MethodsIntersection 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.ResultsFifty-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.ConclusionThe 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."

基金机构：National Natural Science Foundation of China [82072816]; Natural Science Foundation of Shandong Province [ZR2021LZY003]

基金资助正文：This work was supported by the National Natural Science Foundation of China (Grant No. 82072816) and the Natural Science Foundation of Shandong Province (Grant No. ZR2021LZY003).