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HLA-I 表达缺陷与抗原加工机制的关联及其与哈萨克族食管癌患者临床病理特征的关系。

Association of defective HLA-I expression with antigen processing machinery and their association with clinicopathological characteristics in Kazak patients with esophageal cancer.

机构信息

Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.

出版信息

Chin Med J (Engl). 2011 Feb;124(3):341-6.

Abstract

BACKGROUND

It has been confirmed that defective expression of human leukocyte antigen class I (HLA-I) molecules can contribute to the immune evasion of cancer cells in some types of cancer. The aim of this study was to examine the expression of HLA class I antigen and the antigen-processing machinery (APM) components in esophageal squamous cell carcinoma (ESCC) and their role in high risk human papillomavirus (HPV) infection, and to analyze their association with histopathological characteristics in the Kazak ethnic group.

METHODS

A total of 50 formalin-fixed, paraffin-embedded ESCC lesions were collected from the First Affiliated Hospital of Xinjiang Medical University, China. The expression levels of HLA-I antigen and APM components were determined by immunohistochemistry; the HPV DNA were detected using polymerase chain reaction (PCR).

RESULTS

A high frequency of down-regulation or loss of expression of HLA and APM components were found in esophageal cancer in Kazak people. HLA-I, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%, 44%, 48%, 40%, 52%, 32% and 20% of ESCC lesions then, respectively. The loss of expression of HLA-I antigen was significantly correlated with part of the APM components and positively correlated with high risk HPV16 infection. TAP1, CNX, LMP7, Erp57 and Tapasin loss were significantly associated with tumor grading, lymph node metastasis and depth of invasion (P < 0.05).

CONCLUSION

Our results suggest that APM component defects are a mechanism underlying HLA-I antigen down-regulation in ESCC lesions, and indicate that the loss expression of HLA-I and APM components will become an important marker of ESCC and analysis of HLA-I and APM component expression can provide useful prognostic information for patients with ESCC from the Kazak ethnic group.

摘要

背景

已证实人类白细胞抗原 I 类(HLA-I)分子表达缺陷可导致某些类型癌症中的癌细胞免疫逃逸。本研究旨在检测哈萨克族人群食管鳞状细胞癌(ESCC)中 HLA-I 抗原和抗原加工机制(APM)成分的表达及其与高危型人乳头瘤病毒(HPV)感染的关系,并分析其与组织病理学特征的相关性。

方法

收集中国新疆医科大学第一附属医院 50 例福尔马林固定、石蜡包埋的 ESCC 病变。采用免疫组织化学法检测 HLA-I 抗原和 APM 成分的表达水平;采用聚合酶链反应(PCR)检测 HPV DNA。

结果

哈萨克族食管鳞癌中 HLA 和 APM 成分的下调或缺失频率较高。HLA-I、TAP1、CNX、LMP7、Erp57、Tapasin 和 ERAP1 在 68%、44%、48%、40%、52%、32%和 20%的 ESCC 病变中下调。HLA-I 抗原表达缺失与部分 APM 成分显著相关,且与高危 HPV16 感染呈正相关。TAP1、CNX、LMP7、Erp57 和 Tapasin 缺失与肿瘤分级、淋巴结转移和浸润深度显著相关(P<0.05)。

结论

本研究结果提示 APM 成分缺陷是 ESCC 病变中 HLA-I 抗原下调的机制之一,表明 HLA-I 和 APM 成分表达缺失将成为 ESCC 的重要标志物,分析 HLA-I 和 APM 成分的表达可为哈萨克族 ESCC 患者提供有价值的预后信息。

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