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土耳其人群中非小细胞肺癌端粒酶逆转录酶(TERT)启动子突变的临床病理及预后相关性研究

Investigation of clinicopathological and prognostic association of TERT promoter mutation in non-small cell lung cancer in a Turkish population.

作者信息

Dülger Onur, Yaylim Ilhan, Yilmaz Ismail, Sen Fatma, Öz Büge

机构信息

Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

Department of Pathology, Abdulhamid Han Research and Training Hospital, University of Health Sciences, Istanbul, Turkey.

出版信息

Pol J Pathol. 2025;76(1):38-46. doi: 10.5114/pjp.2025.149380.

DOI:10.5114/pjp.2025.149380
PMID:40755329
Abstract

Non-small cell lung cancer (NSCLC) is characterized by a complex and heterogeneous molecular basis. Telomerase reverse transcriptase ( TERT ) gene promoter mutations have been implicated in various cancer types. We aimed to investigate the status of TERT promoter region mutations in NSCLCs and determine associations of clinicopathological connections, driver mutations, programmed death-ligand 1 (PD-L1) expression, and overall survival (OS) in the Turkish population. The study included 186 patients diagnosed with NSCLC at a tertiary care center pathology department between 2017 and 2022. TERT promoter mutations were present in 2.7% and associated with old age ( p = 0.015). The levels of PD-L1 expression were higher in TERT mutants ( p = 0.016). TERT mutants had shorter median OS than wild types ( p = 0.006) and TERT mutation was an independent risk factor ( p = 0.004). TERT and EGFR mutations may co-occur and be associated with shorter median OS in patients who continue to receive EGFR treatment ( p < 0.001). TERT promoter mutations were associated with high PD-L1 expression and adverse prognosis in NSCLC. In addition, they may play a major role in patients' poor clinical outcomes during EGFR therapy. In conclusion, TERT may be a significant parameter for future follow-up and treatment selection of NSCLC.

摘要

非小细胞肺癌(NSCLC)具有复杂且异质性的分子基础。端粒酶逆转录酶(TERT)基因启动子突变与多种癌症类型有关。我们旨在调查土耳其人群中NSCLC患者TERT启动子区域突变的状况,并确定其与临床病理联系、驱动基因突变、程序性死亡配体1(PD-L1)表达及总生存期(OS)之间的关联。该研究纳入了2017年至2022年间在一家三级医疗中心病理科诊断为NSCLC的186例患者。TERT启动子突变的发生率为2.7%,且与老年相关(p = 0.015)。TERT突变体中PD-L1表达水平更高(p = 0.016)。TERT突变体的中位OS短于野生型(p = 0.006),且TERT突变是一个独立危险因素(p = 0.004)。TERT和表皮生长因子受体(EGFR)突变可能同时出现,并与继续接受EGFR治疗患者的较短中位OS相关(p < 0.001)。TERT启动子突变与NSCLC中高PD-L1表达及不良预后相关。此外,它们可能在EGFR治疗期间患者不良临床结局中起主要作用。总之,TERT可能是NSCLC未来随访和治疗选择的一个重要参数。

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