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

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• 作者：Marina Schena^a ; ¹ ; Simonetta Guarrera^b ; ¹ ; Lucio Buffoni^a ; Angelica Salvadori^a ; Floriana Voglino^b ; Alessandra Allione^b ; Giancarlo Pecorari^c ; Enrico Ruffini^d ; Paolo Garzino-Demo^a ; Sara Bustreo^a ; Lorena Consito^a ; Paolo Bironzo^a ; Giuseppe Matullo^b ; ^e ; ^{giuseppe.matullo@unito.it}
• 关键词：NSCLC ; non-small cell lung cancer ; HNSCC ; squamous cell carcinoma of the head and neck ; NER ; nucleotide excision repair ; RT-qPCR ; reverse transcription-quantitative polymerase chain reaction ; RQ ; relative quantification ; Cq ; quantification cycle
• 刊名：DNA Repair
• 出版年：2012
• 期刊代码：121_15687864
• 类别：ch
• 出版时间：1 April, 2012
• 卷：11
• 期：4
• 页码：374-380
• 文件大小：243 K

摘要

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.