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研究胆管癌患者中 VEGF、miR-145-3p 和 miR-101-3p 的表达。

Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma.

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Medicine of São José do Rio Preto, FAMERP, São José do Rio Preto-SP, Brazil.

Department of Gastroenterology, State University of Campinas UNICAMP, Campinas-SP, Brazil.

出版信息

Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2233-2241. doi: 10.31557/APJCP.2022.23.7.2233.

Abstract

INTRODUCTION

Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Several factors, such as epigenetic changes in promoter genes, gene expression, and microRNAs (miR), can contribute to genomic instability in cancer. This study aimed at evaluating the expression of VEGF, miRs 145-3p, and 101-3p in patients with CCA and their potential as biomarkers for diagnosis and prognosis of CCA.

MATERIAL AND METHODS

Sixty two patients were studied. Out of these 62 patients, 41 cases had confirm CCA and 21 cases had hepatopathies complications. The RNA was extracted from a paraffined tissue block, and then the synthesis of cDNA was performed. The analysis of the expression of VEGF, miR-145-3p, and miR-101-3p was carried out by polymerase chain reaction in real time.  Results: The findings revealed that miRs 145-3p and 101-3p were under expressed in the case group compared to the control group (0.46; 0.17; P = 0.0001, respectively). VEGF was overexpressed in the case group compared to the control group (11.8; P = 0.0001). An increase in miR-145-3p expression level was observed in patients with perihilar CCA compared to those with distal CCA (0.51 ± 0.41; 0.17 ± 0.13; P = 0.0698). Survival rate analysis showed that 41.9% of patients with intrahepatic CCA and 31.5% of patients with extrahepatic CCA were free from death within 11 months, leading to a significant difference (P> 0.05).

CONCLUSION

The underexpression of miRNAs, tumor suppressors, the overexpression of VEGF, smoking, and aging were associated with CCA based on our findings. It seems that the reduced expression of the studies miRNAs and increased expression of VEGF can contribute to a decrease in survival rate of patients with tumor in their intrahepatic bile ducts.

摘要

简介

胆管癌(CCA)是原发性肝癌的第二大常见类型。多种因素,如启动子基因的表观遗传改变、基因表达和 microRNAs(miR),都可能导致癌症的基因组不稳定。本研究旨在评估 VEGF、miRs 145-3p 和 101-3p 在 CCA 患者中的表达及其作为 CCA 诊断和预后生物标志物的潜力。

材料和方法

研究了 62 名患者。其中 41 例为确诊 CCA,21 例为肝病变并发症。从石蜡组织块中提取 RNA,然后进行 cDNA 合成。通过实时聚合酶链反应分析 VEGF、miR-145-3p 和 miR-101-3p 的表达。结果:研究结果表明,与对照组相比,病例组中 miR-145-3p 和 miR-101-3p 的表达水平降低(0.46;0.17;P=0.0001)。与对照组相比,病例组中 VEGF 的表达水平升高(11.8;P=0.0001)。与远侧 CCA 患者相比,肝门周围 CCA 患者 miR-145-3p 表达水平升高(0.51±0.41;0.17±0.13;P=0.0698)。生存率分析显示,11 个月内肝内 CCA 患者的 41.9%和肝外 CCA 患者的 31.5%无死亡,差异有统计学意义(P>0.05)。结论:根据我们的研究结果,miRNA 的下调、肿瘤抑制因子的下调、VEGF 的上调、吸烟和衰老与 CCA 相关。研究表明,miRNAs 的表达下调和 VEGF 的表达上调可能导致胆管内肿瘤患者的生存率降低。

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