Low Expression Levels of SLC22A12 Indicates a Poor Prognosis and Progresses Clear Cell Renal Cell Carcinoma.
Low Expression Levels of SLC22A12 Indicates a Poor Prognosis and Progresses Clear Cell Renal Cell Carcinoma.
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SLC22A12 的低表达水平表明预后不良并进展为透明细胞肾细胞癌
DOI：
10.3389/fonc.2021.659208
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Xu J;Liu Y;Liu J;Shou Y;Xiong Z;Xiong H;Xu T;Wang Q;Liu D;Liang H;Yang H;Yang X;Zhang X
透明细胞肾细胞癌（ccRCC）占所有肾癌的约4/5。细胞内稳态的微小变化的累积可能是ccRCC的一个原因。因此，我们从癌症基因组图谱（TCGA）数据库下载了肾细胞癌（KIRC）队列的RNA测序和生存数据。单因素和多因素考克斯回归分析发现19个肾脏特异性差异表达基因（DEG），其中溶质携带者家族22成员12（SLC 22 A12）是总生存期（OS）和无病生存期（DFS）的独立预后预测因子。与正常组织相比，SLC 22 A12在肿瘤组织中的表达较低。此外，SLC 22 A12低表达组的患者比高表达组具有更高的病理分期和更差的生存率。此外，癌组织/细胞和相应正常对照的qRT-PCR测定、免疫印迹试验（IBT）和免疫组织化学（IHC）分析证实，SLC 22 A12在ccRCC中下调。受试者操作特征（ROC）曲线显示，SLC 22 A12的低表达水平可以是ccRCC的良好诊断标志物（AUC=0.7258; p <0.0001）。基因集富集分析（GSEA）显示SLC 22 A12表达水平与代谢、细胞周期和肿瘤相关信号通路有关。GO和KEGG分析表明，SLC 22 A12转运多种有机化合物、离子和激素，并参与细胞外结构的组织。此外，SLC 22 A12在体外过表达可通过调节PI 3 K/Akt通路抑制肾癌细胞的增殖、迁移和侵袭。当敲除SLC 22 A12时，这种效应被逆转。总之，作为许多重要代谢物的转运蛋白，SLC 22 A12可能通过其对所述代谢物的影响来影响肿瘤细胞存活。总之，这项研究发现，SLC 22 A12是一种有前途的ccRCC预后和诊断生物标志物。
Clear cell renal cell carcinoma (ccRCC) accounts for approximately 4/5 of all kidney cancers. Accumulation of minor changes in the cellular homeostasis may be one cause of ccRCC. Therefore, we downloaded the RNA sequencing and survival data of the kidney renal cell carcinoma (KIRC) cohort from the Cancer Genome Atlas (TCGA) database. After the univariate and multivariate Cox regression analyses, 19 kidney-specific differentially expressed genes (DEGs) were found. Solute Carrier Family 22 Member 12 (SLC22A12) resulted in an independent prognostic predictor for both overall survival (OS) and disease-free survival (DFS). SLC22A12 expression was lower in tumoral tissue compared to normal tissue. Moreover, patients in the SLC22A12 low expression group had a higher pathological stage and worse survival than the high expression group. Additionally, qRT-PCR assay, immunoblotting test (IBT), and immunohistochemical (IHC) analyses of cancer tissues/cells and the corresponding normal controls verified that SLC22A12 is downregulated in ccRCC. Receiver operator characteristic (ROC) curves showed that the low expression level of SLC22A12 could be a good diagnostic marker for ccRCC (AUC=0.7258; p <0.0001). Gene set enrichment analysis (GSEA) showed that SLC22A12 expression levels are related to metabolism, cell cycle, and tumor-related signaling pathways. GO and KEGG analyses revealed that SLC22A12 transports multiple organic compounds, ions, and hormones and participates in the extracellular structure organization. Furthermore, SLC22A12 over-expression in vitro inhibited the proliferation, migration, and invasion of renal cancer cells by regulating PI3K/Akt pathways. Such effects were reversed when knocking out SLC22A12. In summary, as a transporter for many vital metabolites, SLC22A12 may affect tumor cell survival through its impacts on the mentioned metabolites. In conclusion, this study uncovered that SLC22A12 is a promising prognostic and diagnostic biomarker for ccRCC.
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影响因子：
2.9
作者：
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通讯作者：
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影响因子：
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作者：
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