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DNA repair gene expression level in peripheral blood and tumour tissue from non-small cell lung cancer and head and neck squamous cell cancer patients

机译:非小细胞肺癌和头颈部鳞状细胞癌患者外周血和肿瘤组织中的DNA修复基因表达水平

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Background: The nucleotide excision repair pathway is crucial for cellular DNA integrity and the ERCC1 helicase is also potentially involved in resistance to platinum-based chemotherapy, and high levels of ERCC1 mRNA in tumours have been associated with cisplatin resistance in different human cancers. The aim of this work was to investigate the correlation between DNA repair gene expression levels in tumour tissue, normal tissue and peripheral blood samples from patients with two common human cancers, non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (HNSCC), to test if blood gene expression could be a proxy for tumour tissue gene expression to predict response to platinum-based chemotherapy. Methods: Using RT-qPCR we determined ERCC1, ERCC2, ERCC4, XPA, XPC, XRCC1, XRCC3, APEX, OGG1, MGMT mRNA levels in fresh NSCLC, normal lung and HNSCC tissue, as well as blood, from NSCLC and HNSCC patients who were treated surgically. Results: Target gene expression in NSCLC and HNSCC tissue was higher than in blood. A statistically significant correlation (p< 0.05) was found between target gene mRNA expression in tumour tissue and blood, in particular ERCC1, MGMT, XPC, XRCC1 and XRCC3 in NSCLC and APEX, ERCC1, ERCC2, ERCC4, XRCC1 and XRCC3 in HNSCC. Conclusions: The existence of a significant correlation between blood and tumour tissue expression of some genes of clinical interest, such as ERCC1 in NSCLC and HNSCC, could allow the introduction in clinical practice of a simple test that would measure mRNA levels of DNA repair genes in peripheral blood samples instead of tissue samples to determine prognostic and predictive factors in NSCLC and HNSCC patients.
机译:背景:核苷酸切除修复途径对于细胞DNA的完整性至关重要,ERCC1解旋酶也可能参与对铂类化学疗法的耐药性,并且在不同人类癌症中,肿瘤中高水平的ERCC1 mRNA与顺铂耐药性相关。这项工作的目的是研究来自两种常见人类癌症,非小细胞肺癌(NSCLC)和头部鳞状细胞癌患者的肿瘤组织,正常组织和外周血样本中DNA修复基因表达水平之间的相关性。 (HNSCC),以测试血液基因表达是否可以替代肿瘤组织基因表达,从而预测对铂类化学疗法的反应。方法:使用RT-qPCR,我们从NSCLC和HNSCC患者中新鲜NSCLC,正常肺和HNSCC组织以及血液中的ERCC1,ERCC2,ERCC4,XPA,XPC,XRCC1,XRCC3,APEX,OGG1,MGMT mRNA水平进行了测定接受手术治疗。结果:NSCLC和HNSCC组织中的靶基因表达高于血液。在肿瘤组织和血液中,特别是在NSCLC中的ERCC1,MGMT,XPC,XRCC1和XRCC3和在HNSCC中的APEX,ERCC1,ERCC2,ERCC4,XRCC1和XRCC3之间,在肿瘤组织和血液中的靶基因mRNA表达之间存在统计学上的显着相关性(p <0.05)。结论:在血液和肿瘤组织表达的一些临床相关基因(如NSCLC和HNSCC中的ERCC1)之间存在显着的相关性,可以在临床实践中引入一种简单的检验方法,该方法可以检测DNA修复基因的mRNA水平。外周血样本代替组织样本,以确定NSCLC和HNSCC患者的预后和预测因素。

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