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氧化损伤和端粒长度作为慢性阻塞性肺疾病(COPD)吸烟者肺癌发生的标志物

Oxidative Damage and Telomere Length as Markers of Lung Cancer Development among Chronic Obstructive Pulmonary Disease (COPD) Smokers.

作者信息

Córdoba-Lanús Elizabeth, Montuenga Luis M, Domínguez-de-Barros Angélica, Oliva Alexis, Mayato Delia, Remírez-Sanz Ana, Gonzalvo Francisca, Celli Bartolomé, Zulueta Javier J, Casanova Ciro

机构信息

Department of Internal Medicine, Dermatology and Psychiatry, University of La Laguna, 38296 San Cristóbal de La Laguna, Spain.

Instituto de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), 38029 San Cristóbal de La Laguna, Spain.

出版信息

Antioxidants (Basel). 2024 Jan 26;13(2):156. doi: 10.3390/antiox13020156.

Abstract

Lung cancer (LC) constitutes an important cause of death among patients with Chronic Obstructive Pulmonary Disease (COPD). Both diseases may share pathobiological mechanisms related to oxidative damage and cellular senescence. In this study, the potential value of leucocyte telomere length, a hallmark of aging, and 8-OHdG concentrations, indicative of oxidative DNA damage, as risk biomarkers of LC was evaluated in COPD patients three years prior to LC diagnosis. Relative telomere length measured using qPCR and serum levels of 8-OHdG were determined at the baseline in 99 COPD smokers (33 with LC and 66 age-matched COPD without LC as controls). Of these, 21 COPD with LC and 42 controls had the biomarkers measured 3 years before. Single nucleotide variants (SNVs) in TERT, RTEL, and NAF1 genes were also determined. COPD cases were evaluated, which showed greater telomere length ( < 0.001) and increased serum 8-OHdG levels ( = 0.004) three years prior to LC diagnosis compared to the controls. This relationship was confirmed at the time of LC diagnosis. No significant association was found between the studied SNVs in cases vs. controls. In conclusion, this preliminary study shows that longer leucocyte telomere length and increased 8-OHdG serum levels can be useful as early biomarkers of the risk for future lung cancer development among COPD patients.

摘要

肺癌(LC)是慢性阻塞性肺疾病(COPD)患者死亡的重要原因。这两种疾病可能具有与氧化损伤和细胞衰老相关的病理生物学机制。在本研究中,在肺癌诊断前三年,对COPD患者中白细胞端粒长度(衰老的一个标志)和8-羟基脱氧鸟苷(8-OHdG)浓度(指示氧化DNA损伤)作为肺癌风险生物标志物的潜在价值进行了评估。在99名COPD吸烟者(33名患有肺癌,66名年龄匹配的无肺癌COPD患者作为对照)的基线时,使用qPCR测量相对端粒长度并测定血清8-OHdG水平。其中,21名患有肺癌的COPD患者和42名对照在3年前测量了生物标志物。还确定了TERT、RTEL和NAF1基因中的单核苷酸变异(SNV)。对COPD病例进行评估,结果显示与对照组相比,在肺癌诊断前三年,其端粒长度更长(<0.001),血清8-OHdG水平升高(=0.004)。在肺癌诊断时证实了这种关系。在病例组与对照组中,所研究的SNV之间未发现显著关联。总之,这项初步研究表明,较长的白细胞端粒长度和升高的血清8-OHdG水平可作为COPD患者未来发生肺癌风险的早期生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff07/10886051/4ec7a89196ea/antioxidants-13-00156-g001.jpg

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