研究动态
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乳腺癌组蛋白H1表达特点及预后意义

The characteristics and prognostic significance of histone H1 expression in breast cancer.

发表日期:2024 Jun 08
作者: Ayat G Lashen, Nabeelah Almalki, Michael Toss, Sameer Mirza, Mohammed Imad Malki, Catrin S Rutland, Jennie N Jeyapalan, Andrew R Green, Nigel P Mongan, Srinivasan Madhusudan, Emad A Rakha
来源: PATHOLOGY

摘要:

组蛋白 H1 (H.H1) 参与染色质组织和基因调控,并在许多恶性肿瘤中过度表达,包括乳腺癌 (BC)。本研究提出并评估了 H.H1 表达在 BC 中的预后作用。 H.H1 mRNA 表达在公开可用的 BC 数据集 bc-GenExMiner 数据库 (n=4421) 中进行评估。在特征明确的早期 BC 队列 (n=1311) 中通过免疫组织化学方法评估 H.H1 蛋白表达,并评估其与临床病理学数据和生存结果的关联。在 mRNA 水平上,高 H.H1 mRNA 与基底样 BC 亚型之间存在显着关联,且预后较差。在整个队列和基础类中观察到与较短生存期的相关性。在肿瘤细胞和周围基质中均检测到 H.H1 蛋白表达。 72%的病例中检测到总表达,其中28%在肿瘤细胞核中,44%在基质中。肿瘤 H.H1 高表达与三阴性 BC (TNBC) 亚型 (p=0.007) 以及较短的生存期 (p=0.019) 之间存在很强的相关性,且与肿瘤大小、组织学肿瘤分级和淋巴结等其他变量无关地位。 H.H1 表达与 BC 预后不良相关。鉴于 H.H1 在 TNBC 中的预后作用较差,它可能代表这种侵袭性疾病患者的潜在治疗靶点。Crown 版权所有 © 2024。由 Elsevier B.V 出版。保留所有权利。
Histone H1 (H.H1) is involved in chromatin organisation and gene regulation and is overexpressed in many malignant tumours, including breast cancer (BC). This study proposed and evaluated the prognostic role of H.H1 expression in BC. H.H1 mRNA expression was evaluated in publicly available BC dataset bc-GenExMiner database (n=4421). H.H1 protein expression was assessed immunohistochemically in a well-characterised early-stage BC cohort (n=1311), and associations with clinicopathological data and survival outcomes were evaluated. At the mRNA level, there was a significant association between high H.H1 mRNA and basal-like BC subtype and with poor outcome. The association with shorter survival was observed in the whole cohort and in the basal-like class. H.H1 protein expression was detected in both tumour cells and surrounding stroma. Total expression was detected in 72% of the cases, including 28% in tumour cell nuclei and 44% in the stroma. There was strong association between high tumour H.H1 expression and triple-negative BC (TNBC) subtype (p=0.007) and with shorter survival (p=0.019), independent of other variables including tumour size, histologic tumour grade, and lymph node status. H.H1 expression is associated with poor prognosis in BC. Given poor prognostic role of H.H1 in TNBC, it may represent a potential therapeutic target for patients with this aggressive disease.Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.