SUV39H1 Expression as a Guideline for Omitting Radiotherapy in Lymph Node-positive Triple-negative Breast Cancer Patients.

IF 2.6 4区医学 Q2 GENETICS & HEREDITY

Cancer Genomics & Proteomics Pub Date : 2023-11-01 DOI:10.21873/cgp.20407

Wei-Lun Huang, Chi-Wen Luo, Huei-Shan Lin, Chao-Ming Hung, Fang-Ming Chen, Sin-Hua Moi, Mei-Ren Pan

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引用次数: 0

Abstract

Background/aim: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs.

Materials and methods: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses.

Results: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel.

Conclusion: Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.

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SUV39H1表达作为癌症淋巴结阳性三阴性乳腺癌患者省略放射治疗的指南。

背景/目的：术后放疗（RT）联合化疗（CT）治疗淋巴结阳性（LN+）三阴性癌症（TNBC）的作用仍存在争议。SUV39H1介导的表观遗传学调控与癌症细胞迁移、侵袭、转移和治疗耐药性有关。本研究旨在确定SUV39H1在TNBCs中的作用。材料和方法：从TCGA-BRCA中检索并分析了498个具有SUV39H1RNA-seq图谱的TNBCs；使用X-tile算法将种群分为低、中、高SUV39H1。此外，我们使用MDA-MB-231细胞系进行了体外克隆细胞存活测定，以评估SUV39H1对细胞反应的影响。结果：SUV39H1在TNBC中的表达明显高于正常组织和管腔亚型癌症。值得注意的是，与其他亚型相比，SUV39H1在基底样1（BL1）和免疫调节（IM）亚组中显著表达。与SUV39H1低表达或中等表达的患者相比，省略RT只会恶化SUV39H1高表达患者的无病生存率（DFS）。实验结果表明，SUV39H1被si-SUV39H1抑制，在MDA-MB-231-IV2-1细胞中敲低SUV39H1增强了阿霉素和紫杉醇的细胞毒性。结论：靶向SUV39H1可能为省略RT以避免TNBC的过度治疗和化疗敏感性提供潜在的指导指征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Genomics & Proteomics ONCOLOGY-GENETICS & HEREDITY

CiteScore

5.00

自引率

8.00%

发文量

期刊介绍： Cancer Genomics & Proteomics (CGP) is an international peer-reviewed journal designed to publish rapidly high quality articles and reviews on the application of genomic and proteomic technology to basic, experimental and clinical cancer research. In this site you may find information concerning the editorial board, editorial policy, issue contents, subscriptions, submission of manuscripts and advertising. The first issue of CGP circulated in January 2004. Cancer Genomics & Proteomics is a journal of the International Institute of Anticancer Research. From January 2013 CGP is converted to an online-only open access journal. Cancer Genomics & Proteomics supports (a) the aims and the research projects of the INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH and (b) the organization of the INTERNATIONAL CONFERENCES OF ANTICANCER RESEARCH.