The NER proteins are differentially expressed in ever smokers and in never smokers with lung adenocarcinoma

Medical Oncology and Translational Research, Institut de Cancérologie Gustave Roussy,Villejuif, France.
Annals of Oncology (Impact Factor: 7.04). 04/2009; 20(7):1257-63. DOI: 10.1093/annonc/mdn785
Source: PubMed


The expression levels of excision repair cross-complementation group 1 (ERCC1), replication protein A (RPA) and xeroderma pigmentosum group F (XPF) nucleotide excision repair proteins may be important in the response to platin-based therapy in lung cancer patients. It is not known whether ERCC1, RPA and XPF expression levels differ between ever smokers (ES) and never smokers (NS).
ERCC1, RPA and XPF expression levels were immunohistochemically evaluated in 125 patients with resected lung adenocarcinoma (AC) and carefully reviewed smoking status.
ERCC1 was correlated with XPF (P = 0.001), but not with RPA (P = 0.11). In the univariate analysis, ERCC1 and XPF levels were higher in NS compared with ES (P = 0.004 and P = 0.003, respectively). In the multivariate analysis, the smoking status was predictive of the ERCC1 level [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.03-6.2] after adjustment for variables linked to the smoking status, including age and the presence of bronchioloalveolar (BAC) features. The smoking status was also predictive of both RPA (OR 6.7, 95% CI 1.5-33.3) and XPF levels (OR 12.5, 95% CI 2.9-50) after adjusting for age, sex and BAC features.
In patients with resected lung AC, ERCC1, RPA and XPF expression levels are higher in NS compared with ES.

9 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The main problem for vector quantisation is the codebook generation. The LBG method solves it with an iterative approach. This algorithm needs a long training sequence and an initial approximation of the codebook. These problems may be overcome by using space filling curves, also called Peano's curves, which are mappings from the unitary interval (image point) to the unitary hypercube. By using this kind of mapping the generation of the codebook, is reduced to the computation of the one-dimensional (optimum) quantiser associated to the probability density function (pdf) of the image points on the Hilbert curve. The paper describes the way of applying these mappings: a new algorithm is derived, generating codebooks for vector quantisation, and experimental results on image coding are provided.
    Acoustics, Speech, and Signal Processing, IEEE International Conference on ICASSP '86.; 05/1986
  • [Show abstract] [Hide abstract]
    ABSTRACT: ERCC1 plays a critical role in the repair of lesions in DNA induced by cisplatin. It has been demonstrated that, in patients with resected NSCLC, those with ERCC1-negative tumours had greater benefit from adjuvant chemotherapy than patients with ERCC1-positive tumours. On the other hand, patients with ERCC1-positive tumours have a better prognosis. ERCC1 can be evaluated either by the level of protein expression on immunohistochemical analysis or by quantification of its mRNA expression. At present ERCC1 appears to be a promising biomarker for predicting the benefit of cisplatin based chemotherapy and its modulation could allow sensitisation of tumour cells to this drug. Its use in daily clinical practice requires a further stage of prospective validation studies which are already in progress in patients both with completely resected NSCL or metastatic disease.
    Revue des Maladies Respiratoires 04/2010; 27(4):387-94. DOI:10.1016/j.rmr.2010.03.003 · 0.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Advanced stage non-small cell lung cancer and head and neck squamous cell carcinoma are both treated with DNA damaging agents including platinum-based compounds and radiation therapy. However, at least one quarter of all tumors are resistant or refractory to these genotoxic agents. Yet the agents are extremely toxic, leading to undesirable side effects with potentially no benefit. Alternative therapies exist, but currently there are no tools to predict whether the first-line genotoxic agents will work in any given patient. To maximize therapeutic success and limit unnecessary toxicity, emerging clinical trials aim to inform personalized treatments tailored to the biology of individual tumors. Worldwide, significant resources have been invested in identifying biomarkers for guiding the treatment of lung and head and neck cancer. DNA repair proteins of the nucleotide excision repair pathway (ERCC1) and of the base excision repair pathway (XRCC1), which are instrumental in clearing DNA damage caused by platinum drugs and radiation, have been extensively studied as potential biomarkers of clinical outcomes in lung and head and neck cancers. The results are complex and contradictory. Here we summarize the current status of single nucleotide polymorphisms, mRNA, and protein expression of ERCC1 and XRCC1 in relation to cancer risk and patient outcomes.
    Pharmacogenomics and Personalized Medicine 07/2011; 4(1):47-63. DOI:10.2147/PGPM.S20317
Show more