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磷脂酰肌醇 4,5-二磷酸 3-激酶催化亚单位β作为感染和胆管癌的潜在生物标志物。

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta as a potential biomarker for infection and cholangiocarcinoma.

机构信息

Thammasat University Research Unit in Opisthorchiasis, Cholangiocarcinoma, and Neglected Parasitic Diseases, Thammasat University, Pathum Thani, 12120, Thailand.

Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand.

出版信息

Parasitology. 2022 Feb;149(2):171-180. doi: 10.1017/S0031182021001694. Epub 2021 Oct 5.

Abstract

The human liver fluke Opisthorchis viverrini (Ov), the primary risk factor for cholangiocarcinoma (CHCA), is a parasite endemic to southeast Asian countries. With no effective treatments for CHCA currently available, early diagnosis and treatment of Ov infection remains the only practical method for the prevention of CHCA. In this study, plasma phosphoproteomes of patients in the non-Ov infection, non-cholangiocarcinoma subject group (non-OVCCA), the asymptomatic Ov infected group (OV), and the CHCA group (CCA), were investigated to identify potential biomarkers for Ov infection and CHCA. The AKT signalling pathway was found to be up-regulated. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB), an upstream signalling molecule, was selected as a potential biomarker and evaluated using indirect enzyme-linked immunosorbent assay (ELISA). Results demonstrated evidence that levels of PIK3CB in both the OV group and CCA group was statistically different compared to the non-OVCCA group (P < 0.01). However, the levels of PIK3CB between the OV group and the CCA group were found not to be statistically different. Sensitivity and specificity for OV using OD450 cut-off at >1.570 was 76 and 72%, respectively. For CCA, sensitivity and specificity using OD450 cut-off at >1.398 was 68 and 76%, respectively. Application of indirect ELISA detecting plasma PIK3CB will be of great benefit for screening of opisthorchiasis and CHCA.

摘要

肝片形吸虫(Ov)是人感染华支睾吸虫(Opisthorchis viverrini)的简称,是导致胆管癌(CHCA)的主要危险因素,该寄生虫流行于东南亚国家。目前尚无有效的 CHCA 治疗方法,因此早期诊断和治疗 Ov 感染仍然是预防 CHCA 的唯一实用方法。本研究旨在通过比较非 Ov 感染非 CHCA 对照组(non-OVCCA)、无症状 Ov 感染组(OV)和 CHCA 组(CCA)患者的血浆磷酸化蛋白质组,以鉴定潜在的 Ov 感染和 CHCA 生物标志物。结果发现 AKT 信号通路被上调,上游信号分子磷脂酰肌醇 4,5-二磷酸 3-激酶催化亚基β异构体(PIK3CB)被选为潜在的生物标志物,并采用间接酶联免疫吸附试验(ELISA)进行评估。结果表明,OV 组和 CCA 组的 PIK3CB 水平与 non-OVCCA 组相比均具有统计学差异(P<0.01)。然而,OV 组和 CCA 组之间的 PIK3CB 水平无统计学差异。以 OD450 截断值>1.570 评估 Ov 的敏感性和特异性分别为 76%和 72%。以 OD450 截断值>1.398 评估 CCA 的敏感性和特异性分别为 68%和 76%。间接 ELISA 检测血浆 PIK3CB 对筛查华支睾吸虫病和 CHCA 具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b4b/11010463/4d1601cf6031/S0031182021001694_figAb.jpg

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