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通过生物信息学分析鉴定BCL11A、NTN5和OGN作为乳头状肾细胞癌的诊断生物标志物

Identification of BCL11A, NTN5, and OGN as Diagnosis Biomarker of Papillary Renal Cell Carcinomas by Bioinformatic Analysis.

作者信息

Haghshenas Zahra, Fathi Sina, Ahmadzadeh Alireza, Nazari Elham

机构信息

Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Kidney Cancer VHL. 2025 Feb 28;12(1):12-22. doi: 10.15586/jkc.v12i1.366. eCollection 2025.

Abstract

The prevalence of papillary renal cell carcinomas (PRCCs) is estimated to be between 10% and 15%. At present, there is no effective therapeutic approach available for patients with advanced PRCCs. The molecular biomarkers associated with PRCC diagnoses have been rarely studied compared to renal clear cell carcinomas; therefore, the necessity for the identification of novel molecular biomarkers to aid in the early identification of this disease. Bioinformatics and artificial intelligence technologies have become increasingly important in the search for diagnostic biomarkers for early cancer detection. In this study, three genes-BCL11A, NTN5, and OGN-were identified as diagnostic biomarkers using the Cancer Genome Atlas (TCGA) database and deep learning techniques. To identify the differential expression genes (DEGs), ribonucleic acid (RNA) expression profiles of PRCC patients were analyzed using a machine learning approach. A number of molecular pathways and coexpressions of DEGs have been analyzed and a correlation between DEGs and clinical data has been determined. Diagnostic markers were then determined via machine learning analysis. The 10 genes selected with the highest variable importance value (more than 0.9) were further investigated, with six upregulated (BCL11A, NTN5, SEL1L3, SKA3, TAPBP, SEMA6A) and four downregulated (OGN, ADCY4, SMOC2, CCL23). A combined receiver operating characteristic (ROC) curve analysis revealed that the BCL11A-NTN5-OGN genes, which have specificity and sensitivity values of 0.968 and 0.901, respectively, can be used as a diagnostic biomarker for PRCC. In general, the genes introduced in this study may be used as diagnostic biomarkers for the early diagnosis of PRCC, thus providing the possibility of early treatment and preventing the progression of the disease.

摘要

乳头状肾细胞癌(PRCC)的患病率估计在10%至15%之间。目前,对于晚期PRCC患者尚无有效的治疗方法。与肾透明细胞癌相比,与PRCC诊断相关的分子生物标志物很少被研究;因此,识别新的分子生物标志物以辅助早期诊断该疾病很有必要。生物信息学和人工智能技术在寻找早期癌症检测的诊断生物标志物方面变得越来越重要。在本研究中,利用癌症基因组图谱(TCGA)数据库和深度学习技术,确定了三个基因——BCL11A、NTN5和OGN——作为诊断生物标志物。为了识别差异表达基因(DEG),采用机器学习方法分析了PRCC患者的核糖核酸(RNA)表达谱。分析了许多分子途径和DEG的共表达情况,并确定了DEG与临床数据之间的相关性。然后通过机器学习分析确定诊断标志物。对选择的10个具有最高可变重要性值(超过0.9)的基因进行了进一步研究,其中6个上调(BCL11A、NTN5、SEL1L3、SKA3、TAPBP、SEMA6A),4个下调(OGN、ADCY4、SMOC2、CCL23)。联合受试者工作特征(ROC)曲线分析显示,特异性和敏感性值分别为0.968和0.901的BCL11A-NTN5-OGN基因可作为PRCC的诊断生物标志物。总体而言,本研究中引入的基因可作为PRCC早期诊断的诊断生物标志物,从而为早期治疗和预防疾病进展提供可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05a/11884337/f76f8776bdd6/JKCVHL-12-012-g001.jpg

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