SLC34A1 的低表达与透明细胞肾细胞癌的不良预后相关。

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.

目的：肾透明细胞癌（ccRCC）是一种恶性肾肿瘤，极易发生转移和复发。这种癌症的确切发病机制尚不清楚。本研究旨在鉴定肾透明细胞癌中的新型枢纽基因，并确定其诊断和预后价值。

方法：从多个数据库中获取交集基因，通过蛋白质-蛋白质相互作用分析和功能富集分析，确定与交集基因相关的关键通路。使用 Cytoscape 中的 cytoHubba 插件识别枢纽基因。使用 GEPIA 和 UALCAN 观察 KIRC 和相邻正常组织中枢纽基因的 mRNA 和蛋白表达差异。使用 Wilcoxon 秩和检验分析配对 KIRC 和匹配的非癌样本中枢纽基因的水平。从 HPA 在线数据库中获取 IHC 结果，并根据基因表达水平的中位数将其分为高表达组和低表达组。分析这些组与 KIRC 患者预后的相关性。使用 logistic 回归和 Wilcoxon 秩和检验检测 SLC34A1 水平与临床病理特征的关系。通过绘制受试者工作特征（ROC）曲线并计算曲线下面积（AUC）来评估 SLC34A1 的诊断价值。Cox 回归分析用于分析临床病理特征、SLC34A1 表达与 KIRC 生存率之间的关系。使用 LinkedOmics 获得与 SLC34A1 最相关的基因及其功能富集。从 cBioPortal 网站和 MethSurv 网站分别获取 KIRC 中 SLC34A1 的遗传突变和甲基化水平。

结果：从六个数据集鉴定出 58 个 ccRCC 差异基因，它们主要富集在 10 个功能项和 4 条通路中。共鉴定出 5 个枢纽基因。根据 GEPIA 数据库分析，肿瘤中 SLC34A1、CASR 和 ALDOB 的低表达导致预后不良。SLC34A1 mRNA 的低表达与患者的临床病理特征有关。SLC34A1 在正常组织中的表达可以准确识别肿瘤（AUC 0.776）。SLC34A1 在单变量和多变量 Cox 分析中也被发现是 ccRCC 的独立预测因子。SLC34A1 基因的突变率为 13%。10 个 DNA 甲基化 CpG 位点中的 8 个与 ccRCC 的预后相关。SLC34A1 在 ccRCC 中的表达与 B 细胞、嗜酸性粒细胞、中性粒细胞、T 细胞、TFH 和 Th17 细胞呈正相关，与 Tem、Tgd 和 Th2 细胞呈负相关。

结论：在 KIRC 样本中发现 SLC34A1 的表达水平降低，这预示着 KIRC 的生存率降低。SLC34A1 可能作为 KIRC 患者的分子预后标志物和治疗靶点。