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生物信息学预测和实验验证确定 CAB39L 为肾透明细胞癌的诊断和预后生物标志物。

Bioinformatics Prediction and Experimental Verification Identify CAB39L as a Diagnostic and Prognostic Biomarker of Kidney Renal Clear Cell Carcinoma.

机构信息

Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Zhejiang Engineering Research Center for Urinary Bladder Carcinoma Innovation Diagnosis and Treatment, Hangzhou 310024, China.

出版信息

Medicina (Kaunas). 2023 Apr 6;59(4):716. doi: 10.3390/medicina59040716.

DOI:10.3390/medicina59040716
PMID:37109674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10145756/
Abstract

: Calcium-binding protein 39-like (CAB39L) has been reported to be downregulated and possessed diagnostic and prognostic values in several types of cancer. However, the clinical value and mechanism of CAB39L in kidney renal clear cell carcinoma (KIRC) remain unclear. : Bioinformatics analysis was conducted using different databases including TCGA, UALCAN, GEPIA, LinkedOmics, STRING, and TIMER. One-way variance analysis and -test were chosen to investigate the statistical differences of CAB39L expression in KIRC tissues with different clinical characteristics. The receiver operating characteristic (ROC) curve was chosen to assess the discriminatory capacity of CAB39L. Kaplan-Meier curves were employed for assessing the influence of CAB39L on the progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) of KIRC patients. The independent prognostic significance of clinical parameters for OS such as CAB39L expression in KIRC patients was estimated by Cox analysis. A series of in vitro functional experiments and Western blot (WB) and immunohistochemistry (IHC) were used to validate the relative protein expression and function of CAB39L. : The mRNA and protein levels of CAB39L were relatively downregulated in KIRC samples. Meanwhile, hypermethylation of the CAB39L promoter region was possibly associated with its low expression in KIRC. The ROC curve showed that the mRNA expression of CAB39L had a strong diagnostic value for both early and late KIRC. Kaplan-Meier survival curves indicated that a higher mRNA level of CAB39L predicted good PFS, DSS, and OS. The mRNA expression of CAB39L was an independent prognostic factor (hazard ratio = 0.6, = 0.034) identified by multivariate Cox regression analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis exhibited that CAB39L was mainly associated with substance and energy metabolism. Finally, overexpression of CAB39L impaired the proliferation and metastasis of KIRC cells in vitro. : CAB39L possesses prognostic and diagnostic capacity in KIRC.

摘要

钙结合蛋白 39 样 (CAB39L) 在多种类型的癌症中表达下调，具有诊断和预后价值。然而，CAB39L 在肾透明细胞癌 (KIRC) 中的临床价值和机制尚不清楚。

使用不同的数据库（包括 TCGA、UALCAN、GEPIA、LinkedOmics、STRING 和 TIMER）进行生物信息学分析。选择单向方差分析和 t 检验来研究不同临床特征的 KIRC 组织中 CAB39L 表达的统计学差异。选择受试者工作特征 (ROC) 曲线来评估 CAB39L 的区分能力。Kaplan-Meier 曲线用于评估 CAB39L 对 KIRC 患者无进展生存期 (PFS)、疾病特异性生存期 (DSS) 和总生存期 (OS) 的影响。通过 Cox 分析估计 KIRC 患者中 CAB39L 等临床参数对 OS 的独立预后意义。一系列体外功能实验和 Western blot (WB) 和免疫组织化学 (IHC) 用于验证 CAB39L 的相对蛋白表达和功能。

CAB39L 的 mRNA 和蛋白水平在 KIRC 样本中相对下调。同时，CAB39L 启动子区域的高甲基化可能与其在 KIRC 中的低表达有关。ROC 曲线表明，CAB39L 的 mRNA 表达对早期和晚期 KIRC 均具有较强的诊断价值。Kaplan-Meier 生存曲线表明，CAB39L 的 mRNA 水平较高预示着较好的 PFS、DSS 和 OS。多变量 Cox 回归分析确定，CAB39L 的 mRNA 表达是独立的预后因素（风险比=0.6，P=0.034）。京都基因与基因组百科全书 (KEGG) 和基因本体论 (GO) 分析表明，CAB39L 主要与物质和能量代谢有关。最后，体外过表达 CAB39L 可损害 KIRC 细胞的增殖和转移。

CAB39L 在 KIRC 中具有预后和诊断能力。

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