评估结直肠癌中 microRNA-92a 的表达及其靶蛋白 Bim。
Evaluation of microRNA 92a Expression and Its Target Protein Bim in Colorectal Cancer.
机构信息
Department of Clinical Pathology, National Cancer Institute, Cairo University, Egypt.
Department of Surgical Oncology, National Cancer Institute, Cairo University, Egypt.
出版信息
Asian Pac J Cancer Prev. 2022 Feb 1;23(2):723-730. doi: 10.31557/APJCP.2022.23.2.723.
BACKGROUND
Colorectal cancer is one of the most commonly diagnosed cancers and leading causes of malignancy-related deaths all over the world. MicroRNAs (miRNAs) can regulate more than 60% of human genes, including tumor-stimulating, and -suppressor genes. Therefore, they can promote cancer development and affect risk of malignancy. miR-92a overexpression in CRC enhances tumor proliferation, invasion, and metastasis through downregulating different pro-apoptosis proteins including Bim. This study aimed to assess the role of plasma miR-92a as non-invasive marker in CRC patients, outline correlation between plasma miR-92a and serum Bim, and determine their correlations with clinicopathological parameters in CRC and adenoma patients.
METHODS
A total of 54 newly diagnosed CRC patients, 15 colonic adenoma patients, and 15 age- and sex-matched control subjects were recruited in this study. Plasma miR-92a was assayed by TaqMan qRT-PCR and serum Bim was measured by ELISA.
RESULTS
Statistically significant overexpression of serum miR-92a was observed in CRC patients as compared to adenoma and control groups (p<0.001 each) and lower serum Bim in CRC patients as compared to adenoma and control groups (p=0.001, p <0.001 respectively). The ROC curve analysis showed excellent AUC for plasma miR-92a in discriminating CRC from control (AUC=0.994), and adenoma (AUC=0.993) groups with highest diagnostic performance in discriminating CRC from controls (at cutoff 1.43, sensitivity 98.1%, specificity 93.9%), and adenoma patients (at cutoff 1.78, sensitivity 92.6%, specificity 93.3%). The diagnostic performance in discriminating early from late CRC was good (at cutoff 15, AUC=0.641, sensitivity 61.2%, specificity 80%). A significant negative correlation was evident between plasma miR-92a and serum Bim both in adenoma and CRC groups (P<0.001 for both). Higher plasma miR-92a expression (r=0.275, p=0.044) and lower serum Bim (r=-0.299, p=0.028) were found to be correlated with late CRC stages.
CONCLUSION
Circulating miR-92a and Bim could be promising, non-invasive diagnostic and prognostic biomarkers in CRC.
.
背景
结直肠癌是世界范围内最常见的癌症之一，也是导致恶性肿瘤相关死亡的主要原因。微小 RNA（miRNA）可以调控超过 60%的人类基因，包括肿瘤刺激和抑制基因。因此，它们可以促进癌症的发展，并影响恶性肿瘤的风险。CRC 中 miR-92a 的过表达通过下调不同的促凋亡蛋白（包括 Bim）来增强肿瘤的增殖、侵袭和转移。本研究旨在评估血浆 miR-92a 作为 CRC 患者非侵入性标志物的作用，概述血浆 miR-92a 与血清 Bim 之间的相关性，并确定它们与 CRC 和腺瘤患者的临床病理参数的相关性。
方法
本研究共纳入 54 例新诊断的 CRC 患者、15 例结肠腺瘤患者和 15 名年龄和性别匹配的对照组。采用 TaqMan qRT-PCR 法检测血浆 miR-92a，ELISA 法检测血清 Bim。
结果
与腺瘤和对照组相比，CRC 患者血清 miR-92a 表达显著升高（p<0.001），CRC 患者血清 Bim 水平明显降低（p=0.001，p<0.001）。ROC 曲线分析显示，血浆 miR-92a 区分 CRC 与对照组（AUC=0.994）和腺瘤（AUC=0.993）的 AUC 均为最佳，以区分 CRC 与对照组的诊断性能最佳（在截点 1.43 时，敏感性为 98.1%，特异性为 93.9%）和腺瘤患者（在截点 1.78 时，敏感性为 92.6%，特异性为 93.3%）。区分早期和晚期 CRC 的诊断性能良好（在截点 15 时，AUC=0.641，敏感性为 61.2%，特异性为 80%）。在腺瘤和 CRC 组中均可见血浆 miR-92a 与血清 Bim 之间存在显著的负相关（均为 P<0.001）。较高的血浆 miR-92a 表达（r=0.275，p=0.044）和较低的血清 Bim（r=-0.299，p=0.028）与晚期 CRC 分期相关。
结论
循环 miR-92a 和 Bim 可能是 CRC 有前途的非侵入性诊断和预后生物标志物。
Zotero 插件