The NER proteins are differentially expressed in ever smokers and in never smokers with lung adenocarcinoma
ABSTRACT 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.
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ABSTRACT: The determination of in situ protein levels of ERCC1 with the 8F1 monoclonal antibody is prognostic of survival in patients with non-small cell lung cancer (NSCLC). The authors previously demonstrated that 8F1 recognizes a second nuclear antigen. This antigen was identified and its value as a biomarker of clinical outcomes analyzed. The second antigen was identified by mass spectrometry. Protein identity and antibody specificity were confirmed through knockdown and overexpression experiments. Immunohistochemistry of 187 early-stage NSCLC samples and 60 head and neck squamous cell carcinomas (HNSCCs) was used to examine the influence of the second antigen on 8F1 immunoreactivity and its association with patient outcomes. Choline phosphate cytidylyltransferase-α (CCTα, also known as phosphate cytidylyltransferase 1 choline alpha [PCYT1A], a phospholipid synthesis enzyme regulated by RAS) is the second antigen recognized by 8F1. In NSCLC samples, CCTα contributed (rho, 0.38) to 8F1 immunoreactivity. In samples of squamous cell carcinomas of the lung, CCTα was found to be the dominant determinant of 8F1 immunoreactivity, whereas its contribution in other subtypes of lung cancer was negligible. High expression of CCTα, but not ERCC1, was found to be prognostic of longer disease-free survival (log-rank P = .002) and overall survival (log-rank P = .056). Similarly, in patients with HNSCC, CCTα contributed strongly to 8F1 immunoreactivity (rho, 0.74), and high CCTα expression was found to be prognostic of survival (log-rank P = .022 for disease-free survival and P = .027 for overall survival). CCTα is the second antigen detected by 8F1. High CCTα expression appears to be prognostic of survival in patients with NSCLC who are treated by surgery alone and patients with HNSCC. CCTα is a promising biomarker of patient survival and deserves further study. Cancer. © 2014 American Cancer Society.Cancer 06/2014; 120(12). DOI:10.1002/cncr.28643 · 4.90 Impact Factor
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ABSTRACT: Oxidative stress appears to play an essential role as a secondary messenger in the normal regulation of a variety of physiological processes, such as apoptosis, survival, and proliferative signaling pathways. Oxidative stress also plays important roles in the pathogenesis of many diseases, including aging, degenerative disease, and cancer. Among cancers, lung cancer is the leading cause of cancer in the Western world. Lung cancer is the commonest fatal cancer whose risk is dependent on the number of cigarettes smoked per day as well as the number of years smoking, some components of cigarette smoke inducing oxidative stress by transmitting or generating oxidative stress. It can be subdivided into two broad categories, small cell lung cancer and non-small-cell lung cancer, the latter is the most common type. Distinct measures of primary and secondary prevention have been investigated to reduce the risk of morbidity and mortality caused by lung cancer. Among them, it seems that physical activity and nutrition have some beneficial effects. However, physical activity can have different influences on carcinogenesis, depending on energy supply, strength and frequency of exercise loads as well as the degree of exercise-mediated oxidative stress. Micronutrient supplementation seems to have a positive impact in lung surgery, particularly as an antioxidant, even if the role of micronutrients in lung cancer remains controversial. The purpose of this review is to examine lung cancer in relation to oxidative stress, physical activity, and nutrition.Lung cancer (Amsterdam, Netherlands) 09/2013; 82(3). DOI:10.1016/j.lungcan.2013.09.009 · 3.74 Impact Factor
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ABSTRACT: Le statut tabagique est une donnée essentielle à recueillir lors de la prise en charge d’un patient atteint d’un cancer bronchique. Les patients non-fumeurs représentent environ 15 % des patients atteints d’un cancer bronchique non à petites cellules, plus fréquent chez les femmes et de type adénocarcinome. L’exposition au tabagisme passif ou à des toxiques professionnels pourrait jouer un rôle important. Le cancer bronchique du non-fumeur apparaît être une entité distincte du cancer du poumon du fumeur avec des caractéristiques moléculaires spécifiques comme un taux élevé de mutations du récepteur de l’epidermal growth factor (EGF). De nouvelles cibles moléculaires sont en cours de validation telles que l’inhibition de la protéine de fusion EML4-ALK. La prise en charge thérapeutique du cancer bronchique du non-fumeur s’individualise de celle du sujet fumeur avec une plus grande place actuelle pour les thérapies ciblées (inhibiteurs EGFR, EML4-ALK).La Presse Médicale 04/2011; 40(4):371-378. DOI:10.1016/j.lpm.2011.02.001 · 1.17 Impact Factor