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
DNA REPAIR
Authors: Schena, Marina; Guarrera, Simonetta; Buffoni, Lucio; Salvadori, Angelica; Voglino, Floriana; Allione, Alessandra; Pecorari, Giancarlo; Ruffini, Enrico; Garzino-Demo, Paolo; Bustreo, Sara; Consito, Lorena; Bironzo, Paolo; Matullo, Giuseppe
Abstract
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. (C) 2012 Elsevier B.V. All rights reserved.
Increased expression of ERCC2 gene in head and neck cancer is associated with aggressive tumors: a systematic review and case-control study
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS
Authors: Zafeer, Maryam; Mahjabeen, Ishrat; Kayani, Mahmood Akhtar
Abstract
Introduction: The excision repair cross-complementation group 2 (ERCC2) ATP-dependent helicase is an essential member of the DNA repair pathway. It has been observed to be differentially expressed in different cancers, which shows its involvement in carcinogenesis. Aim: In the present study we have tried to determine the association of expression patterns of this gene with head and neck carcinogenesis. Method: We first carried out a systematic review of the available studies on the role of ERCC2 in head and neck cancer (HNC). In order to test the hypothesis that the expression patterns of XPD/ERCC2 play a critical role in HNC pathogenesis, we then conducted a population based case-control study on 81 head and neck tumor samples and adjacent normal-tissue control samples. Reverse transcriptase polymerase chain reaction (RT-PCR) and quantitative polymerase chain reaction (qPCR) were used to assess ERCC2 deregulation at the mRNA level. Result: Expression analysis showed that the ERCC2 expression level was significantly upregulated (p<0.05) in HNC tissues compared with adjacent normal tissues. Furthermore, the expression pattern of ERCC2 was correlated with the expression pattern of Ki-67 and a significant correlation (r = 0.230, p<0.03) was observed between ERCC2 and Ki-67. Spearman's correlation also showed a significant correlation between ERCC2 expression and tumor stage (r = 0.271, p<0.02) and grade (r = 0.228, p<0.02) of HNC. Conclusions: Our data suggest that deregulation of ERCC2 in HNC has the potential to predict a more aggressive cancer phenotype and may be considered a possible biomarker for improved diagnosis and prognosis of HNC.