Clinical Studies Of RRM1、BRCA1 Expression In Advanced NSCLC Treated With Gemcitabine/Platinum Therapy

[Background and objective]Lung cancer is now the highest incidence of worldwide malignant tumor, the cancer related death first;Non-small Cell Lung Cancer(NSCLC) about 85% of Lung Cancer, about two-thirds of patients diagnosed with new cases have been late(ⅢB/Ⅳ stage), loss of surgical removal of the opportunity.As an important part of comprehensive treatment of chemotherapy, become one of the main treatment of advanced NSCLC. Gemcitabine platinum-based chemotherapy is the current standard for NSCLC first-line therapy, the objective response rate in patients with advanced lung cancer is 30% ~ 40%, the median surial 8 ~ 10 months, 5 years of survival rate lower than 15%, the overall prognosis.DNA is many molecular targets for anti-cancer drugs, anti-cancer drug sensitivity of tumor is closely related to repairation ability of the DNA damage, are the main factors influencing the curative effect of chemotherapy.RRM1 and BRCA1 are two important members of NER system.To solve the problem of GP chemotherapy regimens for the treatment of lung cancer sensitivity, need respectively in two drug sensitivity predicted signs molecular detection, in order to make clear the effect of two drugs.This study design is in two stages.because of various reasons,some patients could not get enough amount of tissue samples for genetic testing.At first minute chromosome maintain protein 5 gene expressing was detected in sputum cells exfoliated.Circulating tumor cell counts of clinical research in non-small cell lung cancer patients has been done. To the diagnosis of non-small cell lung cancer research from different approaches expect to find suitable,convenient, easy, sensitive detection methods to care disease.This research designs for advanced non-small cell lung cancer uses the method of real-time fluorescent quantitative detection of peripheral blood and lung tumor tissue, Results of RRM1 and BRCA1 expression were analyzed with advanced non-small cell lung cancer clinical characteristics, therapeutic and chemotherapy and survival, the relationship between the effect of chemotherapy on GP solution and evaluation.For clinical reasonable chemotherapy regimens, provides the theory basis for implementation of individualized treatment.Ribonucleotide reductase(RR) can ribonucleic acid catalyzed reduction for deoxyribonucleic acid, Ml of RR subunits(RRM) is a nucleotide binding site, control the substrate specificity and enzyme activity, and gemcitabine chemotherapy drugs of nucleotide analogues, such as combining site.Therefore, whether RRM1 the expression level of high and low for screening in patients receiving gemcitabine chemotherapy has the vital significance.Breast cancer susceptibility gene family l(BRCA1) involved in the process of mitosis, as a kind of tumor suppressor genes BRCA1, mainly through the regulation of DNA repairation, m RNA transcription, cell cycle and protein ubiquitin chemical pathways involved in cellular response.Plays an important role in the genetic damage repair, involved in homologous recombination repair and non homologous end connection repair.Retrospective study results suggest known as BRCA1 may be an important prognostic and predictive factors of chemotherapy NSCLC.The aim of this study is based on materials extracted from the peripheral blood of relatively convenient analysis of gene expression, evaluation RRM1, BRCA1 and gemcitabine combined cisplatin chemotherapy for prognosis of the correlation, and evaluate the correlation of gene expression in tumor tissue and peripheral blood, in order to improve the effective drug treatment, further defined peripheral blood related to genetic testing to chemotherapy.[Research methods]Diagnosed with ⅢB/Ⅳ advanced non-small cell lung cancer patients, used gemcitabine/cisplatin of NSCLC standard first-line chemotherapy.In peripheral blood and tumor tissue samples RRM1 and BRCA1 m RNA are detected biological gene in real-time fluorescent quantitative PCR.First of all, patients with RRM1 and BRCA1 m RNA expression and the clinical and pathological characteristics such as gender, age, histopathological type, stage, smoking the relationship is analyzed.Secondly, the scheme of chemotherapy in patients with RRM1 and BRCA1 m RNA expression and curative effect of relations is analyzed.Third, the analysis of the patient’s clinical and pathological characteristics, RRM1 and BRCA1 m RNA expression and the relationship between the survival time.[Results]In the clinical treatment results show that: the effective rate of 36.4%, a progress time is 4.3 months, the median surial was 11.8 months.In the peripheral blood, BRCA1 and RRM1(P = 0.288) between the linear correlation does not exist.In the peripheral blood and tumor tissue RRM1 relative expression exist linear correlation( P < 0.001); BRCA1 there is also a significant linear correlation( P < 0.001);.RRM1, BRCA1 high expression and low expression of the patient’s age, gender, smoking status and TNM staging(ⅢB、Ⅳ) and histopathological types(squamous carcinoma, adenocarcinoma) differences had no statistical significance(P > 0.05).In lung cancer chemotherapy curative effect of the reaction, RRM1 low group is efficient than the high expression, with significant difference statistically significant(P=0.008), BRCA1 expression result is same.The expression in peripheral blood and tumor tissue level analysis results show that the synchronization.[Conclusion]RRM1 lower expression of chemotherapy in patients with NSCLC is higher efficient, longer life.On the analysis of gene expression in peripheral blood is relatively convenient and widely used, can use the gene expression levels of peripheral blood testing, to predict tumor cells of gemcitabine combined platinum chemotherapy reaction.The results will help to select the most suitable for receiving gemcitabine combined cisplatin chemotherapy patients.