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A significant role in the development of lung tumor resistance to drug therapy play so called mono resistance genes that determine resistance/sensitivity of tumor cells to distinct chemotherapeutic agents, they include BRCA1, RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, ABCC5 genes. It is shown that the use of these biomarkers as a criteria to appoint the adequate postoperative chemotherapy is associated with the forecast. However in the course of neoadjuvant chemotherapy change the expression profile of these genes can occur, which can lead to misinterpretation of results. In this regard perspective is the development of new relevant prognostic factors, which take into account occurred molecular genetic alterations in lung tumors after preoperative therapy. We presented the results of the combined treatment of 52 patients with NSCLC IIA - IIIB stage, based on the analysis of chemotherapy resistance/sensitivity gene expression for appointment the suitable drugs. It was found that the lack of expression of ERCC1 gene in lung tumor derived after neoadjuvant chemotherapy is associated with high rates of disease-free survival (P. = 0,00913). Low level expression of RRM1 gene (less than 0.5) is also associated with high rates of patient's survival (log-rank test P. = 0,01808), while a high level is a marker of poor prognosis. It is found that the combination of enhanced expression (>0.5) of any two or three genes: RRM1, ABCC5, TYMS, are the indicators of poor disease-free survival. We have shown that expression of ERCC1 gene is the independent prognostic factor. At zero ERCC1 expression in lung tumors, regardless of high or low level of expression of RRM1, ABCC5, TYMS genes, a high recurrence-free survival is observed. Thus, the data suggest the prognostic significance of the expression of ERCC1, TUBB3, RRM1, ABCC5 and TYMS genes in the lung tumor after neoadjuvant chemotherapy.
References
Трахтенберг А.Х., Колбанов К.И. Рак легкого//Атмосфера. Пульмонология и аллергология. -2008. -№ 4. -С.3-9.
Цыганов М.М., Родионов Е.О., Миллер С.В., Литвяков Н.В. Обоснование использования экспрессионных маркеров для персонализации химиотерапии рака легкого//Антибиотики и химиотерапия. -2015. -Т. 60(9-10). -С. 38-45.
Юмов Е.Ю, Цыганов М.М, Литвяков Н.В., Полищук Т.В. и др. Экспрессия генов множественной лекарственной устойчивости и монорезистентности при немелкоклеточном раке легкого//Сибирский онкологический журнал. -2014. -Т. 61(1). -С. 16-22.
Betticher D.C., Schmitz S.-F.H., Tötsch M. et аi. Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: A multicenter phase II trial//Journal of Clinical Oncology. -2003. -Vol.21(9). -P.1752-1759.
Fujii T., Toyooka S., Ichimura K. et al. ERCC1 protein expression predicts the response of cisplatin-based neoadjuvan chemotherapy in non-small-cell Lung Cancer//Lung Cancer. -2008. -Vol.59(3). -P377-384.
Goldstraw P., Crowley K.J., Chansky D.J. et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours//Journal of Thoracic Oncology. -2007. -Vol. 2 (8). -P. 706-714.
Huang Z.L., Cao X., Luo R.Z. et al. Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study//Oncology Letters. -2016. -Vol. 11 (1). -P. 299-305.
Jakobsen J.N., S0rensen J.B. Intratumor heterogeneity and chemotherapy-induced changes in EGFR status in non-small cell lung cancer//Cancer chemotherapy and pharmacology. -2012. -Vol.69(2). -P289-299.
Jakobsen J.N., Santoni-Rugiu E., Ravn J., S0rensen J.B. Intratumour variation of biomarker expression by immuno-histochemistry in resectable non-small cell lung cancer//European Journal of Cancer. -2013. -Vol. 49 (11). -P. 2494-2503.
Kaplan E.L., Meier P. Nonparametric estimation from incomplete observations//Journal of the American statistical association. -1958. -Vol.53(282). -P. 457-481.
Kucukoztas N., Oguz A., Rahatli S. et al. Correlation of histopahologic response and prognostic markers with survival in locally advanced non-small cell lung cancer patients who have treated with neoadjuvant chemotherapy//Journal of Clinical Oncology. -2015. -Vol. 33 (15).
Litviakov N.V., Cherdyntseva N.V., Tsyganov M.M. et al. Changing the expression vector of multidrug resistance genes is related to neoadjuvant chemotherapy response//Cancer chemotherapy and pharmacology. -2013. -Vol.71(1). -P.153-163.
Pfaffl M.W. A new mathematical model for relative quantification in real-time RT-PCR//Nucleic acids research. -2001. -Vol. 29(9). -P. 45.
Reynolds C., Obasaju C., Schell M.J. et al. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 Protein levels for response prediction in non-small-cell lung cancer//Journal of Clinical Oncology. -2009. -Vol. 27 (34). -P. 5808-5815.
Shatokhina S.N., Zakharova N.M., Dedova M.G. et al. Morphological marker of tumor progression in laryngeal cancer//Voprosy onkologii. -2013. -Vol. 59 (2). -P. 66-70.
Song W.-A., Zhou N.-K., Wang W. et al. Survival benefit of neoadjuvant chemotherapy in non-small cell lung cancer: an updated meta-analysis of 13 randomized control trials//Journal of Thoracic Oncology. -2010. -Vol. 5(4). -P. 510-516.
Stanley K.E. Prognostic factors for survival in patients with inoperable lung cancer//Journal of the National Cancer Institute. -1980. -65(1). -P. 25-32.
Steels E., Paesmans M., Berghmans T. et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis//European Respiratory Journal. -2001. -18(4). -P. 705-719.
Wei C.H., Gorgan T.R., Elashoff D.A. et al. A meta-analysis of gemcitabine biomarkers in patients with pancreatico-biliary cancers//Pancreas. -2013. -Vol.42(8). -P. 1-16.
Zhao H., Zhang H., Du Y, Gu X. Prognostic significance of BRCA1, ERCC1, RRM1, and RRM2 in patients with advanced non-small cell lung cancer receiving chemotherapy//Tumor Biology. -2014. -Vol. 35(12). -P. 12679-12688.
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