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蛋白二硫键异构酶 A3 在埃及膀胱癌患者中的作用演变。

The evolving role of protein disulfide isomerase A3 in Egyptian bladder cancer patients.

机构信息

Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt.

Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt.

出版信息

Gene. 2019 Apr 20;693:76-83. doi: 10.1016/j.gene.2019.01.024. Epub 2019 Jan 29.

Abstract

BACKGROUND

Protein disulfide isomerase A3 (PDIA3), an endoplasmic reticulum protein, is expressed in bladder of BC patients. However, its role in BC has been elusive till now.

OBJECTIVES

This study was conducted to assess whether PDIA3 gene expression was associated with increased odds of BC, in particular muscle-invasive BC (MIBC).

METHODS

Ninety three patients underwent cystoscopy and bladder tumors were biopsied and histologically assessed. Data collected including: patient demographics and clinical characteristics. Biochemical markers: hypoxia inducible factor 1-alpha (HIF-1 α), interleukin 6 (IL-6), advanced oxidation protein products (AOPP), Malondialdehyde (MDA), 8-hydroxy 2-deoxyguanosine (8-OHdG), and reduced glutathione (GSH) and molecular marker PDIA3 gene expression were measured.

RESULTS

According to the tumor grade and stage, 36 patients were found to have MIBC, 27 patients have non MIBC (NMIBC) and 30 patients have no bladder lesions (control group). PDIA3 gene expression level had the largest contribution to a multivariable model for predicting BC, which achieved 89.0% predictive accuracy. The AUC for discriminating MIBC significantly increased from 0.644 to 0.938 when biochemical markers were replaced by molecular PDIA3 marker in the final model.

CONCLUSIONS

Using PDIA3 expression along with prior information of patient's age, bilharzial history with gross hematuria, can help clinicians predict BC, discriminate MIBC and decide consequently the most promising therapeutic management in Egyptian population.

摘要

背景

蛋白质二硫键异构酶 A3(PDIA3)是一种内质网蛋白,在膀胱癌患者的膀胱中表达。然而,其在膀胱癌中的作用至今仍不清楚。

目的

本研究旨在评估 PDIA3 基因表达是否与膀胱癌(尤其是肌层浸润性膀胱癌(MIBC))的发生几率增加相关。

方法

93 例患者接受膀胱镜检查,对膀胱肿瘤进行活检并进行组织学评估。收集的数据包括:患者的人口统计学和临床特征。生化标志物:缺氧诱导因子 1-α(HIF-1α)、白细胞介素 6(IL-6)、高级氧化蛋白产物(AOPP)、丙二醛(MDA)、8-羟基 2-脱氧鸟苷(8-OHdG)和还原型谷胱甘肽(GSH)以及分子标志物 PDIA3 基因表达。

结果

根据肿瘤分级和分期,36 例患者为 MIBC,27 例患者为非 MIBC(NMIBC),30 例患者无膀胱病变(对照组)。PDIA3 基因表达水平对预测膀胱癌的多变量模型有最大的贡献,预测准确率达到 89.0%。当将生化标志物替换为最终模型中的分子 PDIA3 标志物时,用于区分 MIBC 的 AUC 从 0.644 显著增加到 0.938。

结论

在埃及人群中,使用 PDIA3 表达以及患者年龄、埃及血吸虫病史伴肉眼血尿的先验信息,可以帮助临床医生预测膀胱癌,区分 MIBC,并相应地决定最有前途的治疗管理方案。

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