SC Oncologia Medica, San Giovanni Battista Hospital, Turin, Italy.
DNA Repair (Amst). 2012 Apr 1;11(4):374-80. doi: 10.1016/j.dnarep.2012.01.003. Epub 2012 Jan 28.
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.
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.
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.
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.
核苷酸切除修复途径对细胞 DNA 完整性至关重要, ERCC1 解旋酶也可能与铂类化疗耐药有关,肿瘤中高水平的 ERCC1mRNA 与不同人类癌症中顺铂耐药有关。本研究旨在探讨两种常见人类癌症(非小细胞肺癌[NSCLC]和头颈部鳞状细胞癌[HNSCC])患者肿瘤组织、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,以测试血液基因表达是否可以作为肿瘤组织基因表达的替代物,预测对铂类化疗的反应。
使用 RT-qPCR 我们测定了新鲜 NSCLC、正常肺组织和 HNSCC 组织以及 NSCLC 和 HNSCC 患者手术治疗时的外周血中的 ERCC1、ERCC2、ERCC4、XPA、XPC、XRCC1、XRCC3、APEX、OGG1、MGMT mRNA 水平。
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的靶基因 mRNA 表达之间发现了统计学上显著的相关性(p<0.05),特别是在 NSCLC 中的 ERCC1、MGMT、XPC、XRCC1 和 XRCC3 以及 HNSCC 中的 APEX、ERCC1、ERCC2、ERCC4、XRCC1 和 XRCC3。
一些具有临床意义的基因(如 NSCLC 和 HNSCC 中的 ERCC1)在血液和肿瘤组织表达之间存在显著相关性,这可能允许在临床实践中引入一种简单的测试,该测试将测量外周血样本中 DNA 修复基因的 mRNA 水平,而不是组织样本,以确定 NSCLC 和 HNSCC 患者的预后和预测因素。