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HLA-J，一种非假基因，作为乳腺癌治疗反应和生存的新预后标志物。

HLA-J, a Non-Pseudogene as a New Prognostic Marker for Therapy Response and Survival in Breast Cancer.

作者信息

Würfel Franziska M, Wirtz Ralph M, Winterhalter Christoph, Taffurelli Mario, Santini Donatella, Mandrioli Anna, Veltrup Elke, Rübner Matthias, Fasching Peter A, Würfel Wolfgang, Zamagni Claudio

机构信息

STRATIFYER Molecular Pathology GmbH, Cologne, Germany.

Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg (FAU), Erlangen, Germany.

出版信息

Geburtshilfe Frauenheilkd. 2020 Nov;80(11):1123-1133. doi: 10.1055/a-1128-6664. Epub 2020 Nov 6.

DOI:10.1055/a-1128-6664
PMID:33173240
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7647720/
Abstract

The human leukocyte antigen (HLA) genes are cell-surface proteins, essential for immune cell interaction. HLA-G is known for their high immunosuppressive effect and its potential as predictive marker in breast cancer. However, nothing is known about the HLA-J and its immunosuppressive, prognostic and predictive features, as it is assumed to be a "pseudogene" by in silico sequence interpretation. HLA-J, ESR1, ERBB2, KRT5 and KRT20 mRNA expression were analysed in 29 fresh frozen breast cancer biopsies and their corresponding resectates obtained from patients treated with neoadjuvant chemotherapy (NACT). mRNA was analysed with gene specific TaqMan-based Primer/Probe sets and normalized to Calmodulin 2. All breast cancer samples did express HLA-J and frequently increased HLA-J mRNA levels after NACT. HLA-J mRNA was significantly associated with overexpression of the ESR1 mRNA status (Spearman ρ 0,5679; p = 0.0090) and KRT5 mRNA (Spearman ρ 0,6121; p = 0.0041) in breast cancer core biopsies and dominated in luminal B subtype. Kaplan Meier analysis revealed that an increase of HLA-J mRNA expression after NACT had worse progression free survival (p = 0,0096), indicating a counterreaction of tumor tissues presumably to prevent elimination by enhanced immune infiltration induced by NACT. This counterreaction is associated with worse prognosis. To our knowledge this is the first study identifying HLA-J as a new predictive marker in breast cancer being involved in immune evasion mechanisms.

摘要

人类白细胞抗原（HLA）基因是细胞表面蛋白，对免疫细胞相互作用至关重要。HLA - G以其高免疫抑制作用及其作为乳腺癌预测标志物的潜力而闻名。然而，关于HLA - J及其免疫抑制、预后和预测特征却一无所知，因为通过计算机序列分析它被认为是一个“假基因”。在29例接受新辅助化疗（NACT）治疗的患者的新鲜冷冻乳腺癌活检组织及其相应的手术切除标本中，分析了HLA - J、ESR1、ERBB2、KRT5和KRT20的mRNA表达。使用基于TaqMan的基因特异性引物/探针组分析mRNA，并将其标准化为钙调蛋白2。所有乳腺癌样本均表达HLA - J，且在NACT后HLA - J mRNA水平经常升高。在乳腺癌核心活检组织中，HLA - J mRNA与ESR1 mRNA状态的过表达（Spearman ρ 0.5679；p = 0.0090）和KRT5 mRNA（Spearman ρ 0.6121；p = 0.0041）显著相关，且在腔面B亚型中占主导地位。Kaplan - Meier分析显示，NACT后HLA - J mRNA表达增加的患者无进展生存期较差（p = 0.0096），这表明肿瘤组织可能产生了一种反应，以防止因NACT诱导的免疫浸润增强而被清除。这种反应与较差的预后相关。据我们所知，这是第一项将HLA - J鉴定为参与免疫逃逸机制的乳腺癌新预测标志物的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/27862b36f476/10-1055-a-1128-6664-igf08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/86656e84cfc2/10-1055-a-1128-6664-igf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/cfb3b2c418d6/10-1055-a-1128-6664-igf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/b35ac858f6f4/10-1055-a-1128-6664-igf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/8c387615ea9e/10-1055-a-1128-6664-igf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/12061086bb92/10-1055-a-1128-6664-igf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/d638f18a5e34/10-1055-a-1128-6664-igf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/abd88ea36358/10-1055-a-1128-6664-igf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/27862b36f476/10-1055-a-1128-6664-igf08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/86656e84cfc2/10-1055-a-1128-6664-igf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/cfb3b2c418d6/10-1055-a-1128-6664-igf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/b35ac858f6f4/10-1055-a-1128-6664-igf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/8c387615ea9e/10-1055-a-1128-6664-igf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/12061086bb92/10-1055-a-1128-6664-igf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/d638f18a5e34/10-1055-a-1128-6664-igf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/abd88ea36358/10-1055-a-1128-6664-igf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f9/7647720/27862b36f476/10-1055-a-1128-6664-igf08.jpg

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