BACH1在非小细胞肺癌中的临床意义
Clinical Relevance of BACH1 Expression in Non-Small Cell Lung Cancer.
作者
作者单位
- Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany.
- Department of Thoracic Surgery, Thoraxklinik at Heidelberg University Hospital, Heidelberg, Germany.
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
摘要
中文
BTB and CNC homolog 1（BACH1）是一种氧化还原敏感的转录因子，已在多种肿瘤中被证实参与肿瘤进展、代谢重编程及治疗耐药。然而，其在非小细胞肺癌（NSCLC）中的预后意义及在治疗耐药中的作用尚不明确。本研究在手术切除的肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）组织及配对的非肿瘤肺组织中定量检测了BACH1 mRNA和蛋白表达，并将其与临床病理参数、辅助化疗状态及无病生存期（DFS）进行相关性分析。预后价值采用Kaplan-Meier法和多因素Cox回归分析进行评估。体外实验中，在7种NSCLC细胞系中评估了BACH1的表达，并通过Annexin V凋亡实验检测顺铂敏感性；在H1975和H1435细胞中沉默BACH1后评估其对顺铂反应、迁移及克隆形成能力的影响。结果显示，BACH1在LUAD和LUSC中的表达低于配对正常肺组织，但在III期肿瘤及接受辅助化疗的患者中表达升高。在LUAD中，BACH1高表达与较短的无病生存期相关，尤其在接受辅助化疗的患者中更为显著。BACH1表达与化疗之间存在显著交互作用，提示基于顺铂的治疗获益因BACH1状态不同而存在差异。在7种NSCLC细胞系中，BACH1表达与顺铂耐药性呈正相关（r=0.44, p=0.035）。沉默BACH1可增强顺铂诱导的细胞死亡，抑制H1975和H1437细胞的迁移及克隆形成能力。综上，本研究结果提示BACH1可作为化疗LUAD患者的潜在预后和预测生物标志物，并支持BACH1在介导顺铂耐药中发挥功能性作用。
English
BTB and CNC homolog 1 (BACH1) is a redox-sensitive transcription factor implicated in tumor progression, metabolic reprogramming, and therapy resistance in several cancers. However, its prognostic significance and role in therapy resistance in non-small cell lung cancer (NSCLC) remain unclear. BACH1 mRNA and protein expression were quantified in resected lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) tissues and matched non-tumor lung tissues and correlated with clinicopathological parameters, adjuvant chemotherapy status, and disease-free survival (DFS). Prognostic value was assessed using Kaplan-Meier and multivariate Cox regression analyses. In vitro, BACH1 expression was evaluated in seven NSCLC cell lines. Cisplatin sensitivity was determined by Annexin V apoptosis assays, and BACH1 silencing in H1975 and H1437 cells was used to assess effects on cisplatin response, migration, and colony formation. BACH1 expression was lower in LUAD and LUSC than in matched normal lung tissues but was higher in stage III tumors and in patients receiving adjuvant chemotherapy. In LUAD, high BACH1 expression was associated with shorter DFS, particularly in adjuvant chemotherapy. A significant interaction between BACH1 expression and chemotherapy suggested that the benefit of cisplatin-based treatment differed according to BACH1 status. Across seven NSCLC cell lines, BACH1 expression positively correlated with cisplatin resistance (r = 0.44, p = 0.035). BACH1 silencing enhanced cisplatin-induced cell death, suppressed migration, and clonogenic growth in H1975 and H1437 cells. Collectively, these findings identify BACH1 as a potential prognostic and predictive biomarker in chemotherapy-treated LUAD and support a functional role for BACH1 in mediating cisplatin resistance.
分类与指标
- 研究类型
- 临床研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 4.9
- 新锐分区
- 2区