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三结构域蛋白 59 的评估及其在良性肠病和结直肠癌中的诊断效用。

Evaluation of tripartite motif 59 and its diagnostic utility in benign bowel diseases and colorectal cancer.

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Department of Medical Biochemistry and Molecular Biology, Armed forces collage of Medicine (AFCM), Cairo, Egypt.

出版信息

J Biochem Mol Toxicol. 2022 Jul;36(7):e23065. doi: 10.1002/jbt.23065. Epub 2022 Apr 4.

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in developing countries. Tripartite motif-59 (TRIM59) a member of the TRIM ubiquitin ligase family, is a surface molecule that regulates biological processes such as cell proliferation, apoptosis, and tumorigenesis. Previous studies reported that TRIM59 expression was upregulated in human CRC, however, the expression pattern and role of TRIM59 in benign colorectal lesions remain unclear. Sixty patients diagnosed with CRC and 60 patients with benign lesions (Crohn's disease, ulcerative colitis, adenoma, and familial adenomatous polyposis) were recruited to the present study. TRIM59 gene expression was assessed by real-time quantitative polymerase chain reaction. Expression of TRIM59 protein and p-AKT were determined using, enzyme-linked immunoassay while p53 expression was detected by immunohistochemistry. Antioxidant/oxidant role of glutathione (GSH)/malondialdehyde (MDA) were evaluated by colorimetric methods in all of the studied groups. Our results showed upregulated expressions of TRIM59 gene and protein levels in CRC tissues and benign colonic lesions compared to nontumor tissues. Their levels were higher in inflammatory compared to noninflammatory bowel lesions. There were significant interrelations among TRIM59 gene expression, protein levels, tumor, node, metastasis staging, and the presence of metastasis (p < 0.0001). Receiver-operator characteristic curve analyses showed that at the cutoff point of 2.5 TRIM59 mRNA expression can discriminate between CRC cases and benign bowel group (area under the curve [AUC]: 0.639, sensitivity: 86.7%, specificity: 41.7%), and between CRC and controls (AUC: 0.962, sensitivity: 90%, specificity: 91.7%). TRIM59 could be a potential biomarker in the early detection, diagnosis, and treatment of benign colonic lesions and CRC.

摘要

结直肠癌(CRC)是发展中国家癌症相关死亡的第二大主要原因。三结构域蛋白 59(TRIM59)是 TRIM 泛素连接酶家族的成员,是一种表面分子,调节细胞增殖、凋亡和肿瘤发生等生物学过程。先前的研究表明,TRIM59 在人 CRC 中表达上调,然而,TRIM59 在良性结直肠病变中的表达模式和作用尚不清楚。本研究纳入了 60 例 CRC 患者和 60 例良性病变患者(克罗恩病、溃疡性结肠炎、腺瘤和家族性腺瘤性息肉病)。通过实时定量聚合酶链反应评估 TRIM59 基因表达。采用酶联免疫吸附试验测定 TRIM59 蛋白和磷酸化 AKT 的表达,免疫组织化学法检测 p53 表达。用比色法评估所有研究组的谷胱甘肽(GSH)/丙二醛(MDA)的抗氧化/氧化作用。结果显示,CRC 组织和良性结肠病变组织中 TRIM59 基因和蛋白水平均上调,且炎症性肠病病变组织高于非炎症性肠病病变组织。TRIM59 基因表达与肿瘤、淋巴结、转移分期和转移存在显著相关性(p<0.0001)。受试者工作特征曲线分析显示,在 2.5 的截断点处,TRIM59 mRNA 表达可区分 CRC 病例和良性肠组(曲线下面积 [AUC]:0.639,敏感性:86.7%,特异性:41.7%)和 CRC 与对照组(AUC:0.962,敏感性:90%,特异性:91.7%)。TRIM59 可能是早期检测、诊断和治疗良性结肠病变和 CRC 的潜在生物标志物。

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