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硫氧还蛋白 1 和过氧化物酶在宫颈鳞癌中的表达及其在新辅助化疗中的预测作用。

Expression of thioredoxin 1 and peroxiredoxins in squamous cervical carcinoma and its predictive role in NACT.

机构信息

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China.

Department of Gynecology, the First Affiliated Hospital of Wenzhou Medical University, Shangcaicun Road, Wenzhou, 325000, China.

出版信息

BMC Cancer. 2019 Aug 30;19(1):865. doi: 10.1186/s12885-019-6046-x.

Abstract

BACKGROUND

This study aims to investigate the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 in bulky cervical squamous carcinoma and its predictive role in cisplatin-based neoadjuvant chemotherapy.

METHODS

Initially, the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 protein was analyzed in 13 human cervical squamous cancer tissues and their paired adjacent non-cancerous tissues by western-blotting and immunohistochemistry. Then, correlation between the expression of thioredoxin 1, peroxiredoxin 1, peroxiredoxin 2 and responses to cisplatin-based neoadjuvant chemotherapy was analyzed in 35 paired tumor samples (pre- and post-chemotherapy) from bulky cervical squamous cancer patients by immunohistochemistry.

RESULTS

A clinical response occurred in 48.6% (17/35) of patients, including 14.3% (5/35) with a complete response and 34.3% (12/35) with a partial response. The expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 was much higher in cervical squamous cancer tissues compared with paired adjacent non-cancerous tissues by western-blotting and immunohistochemistry. Additionally, the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 was significantly up-regulated in post-chemotherapy tissues compared to pre-chemotherapy cervical cancer tissues. High levels of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 were associated with a poor chemotherapy response in cervical squamous cancer patients.

CONCLUSIONS

Thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 are frequently over-expressed in cervical squamous cancer. High expression levels of these proteins were related to a poor response to cisplatin-based neoadjuvant chemotherapy. The present study is the first report that thioredoxin peroxidase system may serve as a prediction of the responses to neoadjuvant chemotherapy in cervical squamous cancer.

摘要

背景

本研究旨在探讨硫氧还蛋白 1、过氧化物酶 1 和过氧化物酶 2 在大体积宫颈鳞癌中的表达及其在顺铂为基础的新辅助化疗中的预测作用。

方法

首先,通过 Western blot 和免疫组织化学分析 13 例人宫颈鳞癌组织及其配对的癌旁正常组织中硫氧还蛋白 1、过氧化物酶 1 和过氧化物酶 2 蛋白的表达。然后,通过免疫组织化学分析 35 例大体积宫颈鳞癌患者化疗前后配对肿瘤样本(化疗前和化疗后)中硫氧还蛋白 1、过氧化物酶 1 和过氧化物酶 2 的表达与顺铂为基础的新辅助化疗反应的相关性。

结果

48.6%(17/35)的患者出现临床反应,包括完全缓解率 14.3%(5/35)和部分缓解率 34.3%(12/35)。Western blot 和免疫组织化学结果显示,宫颈鳞癌组织中硫氧还蛋白 1、过氧化物酶 1 和过氧化物酶 2 的表达明显高于配对的癌旁正常组织。此外,与化疗前宫颈癌组织相比,化疗后组织中硫氧还蛋白 1、过氧化物酶 1 和过氧化物酶 2 的表达明显上调。高水平的硫氧还蛋白 1、过氧化物酶 1 和过氧化物酶 2 与宫颈鳞癌患者化疗反应不良相关。

结论

硫氧还蛋白 1、过氧化物酶 1 和过氧化物酶 2 在宫颈鳞癌中常过度表达。这些蛋白的高表达水平与顺铂为基础的新辅助化疗反应不良相关。本研究首次报道,硫氧还蛋白过氧化物酶系统可能作为宫颈鳞癌新辅助化疗反应的预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9155/6716838/4286c7112192/12885_2019_6046_Fig1_HTML.jpg

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