The Role Of RecQL4 In Chemotherapy Resistance For Small Cell Lung Cancer

The morbidity and mortality of lung cancer is the highest in the world.Small Cell Lung Cancer is a special type of Lung Cancer,accounting for about 15% of Lung Cancer.Since blood transfer can occur in the early stage,most of the patients have developed advanced stage and extensive systemic metastasis.Although SCLC is sensitive to chemotherapy in the early stage,with the treatment of chemotherapy,multidrug resistance can easily occur,resulting in the failure of chemotherapy.In recent years,the incidence of small cell lung cancer has been increasing year by year,but there is no breakthrough in treatment。As a member of the human RecQ helicase family,RecQL4 plays an important role not only in DNA replication,transcription and damage repair pathways,but also plays an important role in regulating tumor chemotherapy resistance.The studies show that the RecQL4 protein has a dual role,which is not only the lack of function that promotes certain types of tumors,but the high expression of the abnormality can also promote the progress of the human tumor.Therefore,RecQL4 can be used as an important potential application target in tumor clinical treatment to predict the sensitivity of chemotherapy,so as to improve the efficacy of clinical treatment and improve the prognosis of patients.One of the important mechanisms of SCLC chemotherapy resistance is the up-regulation of MDR expression in multi-drug resistance genes,especially the increase of MDR1 gene.MDR1 mediated drug efflux of ATP-dependent function can be some anti-cancer drugs pumps out to the body,so that the drug concentrations within the tumor cells decreased,cytotoxic drugs to be weaken or disappear,so that chemotherapy failure.But so far there has been no report on the relationship between the expression levels of RecQL4 and MDR1 and the chemotherapy resistance in small cell lung cancer.In this study,the expression levels of RecQL4 and MDR1 in the pathological tissues of 31 patients with initial SCLC were detected by immunohistochemistry,to analyze its relationship with chemotherapy resistance,in order to assess the chemotherapy effect of patients with SCLC in the future,better guide clinical individualized treatment to provide the reference.Methods:31 cases of SCLC patients with initial treatment were collected from the oncology department of Bethune International Peace Hospital PLA from September.2011 to September.2016.The expression of RecQL4 and MDR1 in the pathological sections of 31 cases of SCLC was detected by immunohistochemistry method,and the relationship between them and clinicopathological features,chemotherapy resistance and prognosis was analyzed.Results:1.The overall response rate of 31 cases of SCLC patients was 45.2%.2.The differences between the expression of RecQL4 and the patient’s age,gender,smoking history,the combination of chest water,lymph node metastasis,and clinical staging were not statistically significant(P > 0.05),but there was a significant statistical significance in the efficacy of chemotherapy(P < 0.05);The expression level of RecQL4 was negatively correlated with the TTP(P<0.05,r=﹣0.81).3.The median PFS and OS of the RecQL4 high expression group were significantly shorter than the RecQL4 low expression group,and the difference was statistically significant(P < 0.05).4.The differences between the expression of MDR1 and the patient’s age,gender,smoking history,the combination of chest water and lymph node metastasis were not statistically significant(P > 0.05),but there was a significant statistical significance in clinical staging and the efficacy of chemotherapy(P < 0.05);The expression level of MDR1 was negatively correlated with the TTP(P<0.05,r=﹣0.76).5.The median PFS and OS of the MDR1 low expression group were significantly longer than the MDR1 high expression group,and the difference was statistically significant(P < 0.05).6.The expression level of RecQL4 was positively correlated with the expression level of MDR1(P<0.05,r=0.61).7.The clinical stage was extensive,MDR1 high expression and RecQL4 high expression were independent risk factors for prognosis in SCLC patients.Conclusion:1.RecQL4 expression of relatively high SCLC patients was more likely to be resistant to chemotherapy,short survival and poor prognosis.2.MDR1 expression of relatively high SCLC patients had poor response to chemotherapy,it’s easy to develop resistance during chemotherapy,high risk of recurrence after chemotherapy,short survival and poor prognosis.3.The expression model of RecQL4-MDR1 can be used to predict the prognosis of small cell lung cancer and to treat drug-resistant molecular phenotypes.The action mechanism was that RecQL4 may induce the overexpression of MDR1,a multidrug-resistant gene,to promote the resistance of SCLC patients to chemotherapy.4.RecQL4 is closely related to SCLC chemotherapy resistance,and the expression of RecQL4 can be used as a reliable indicator to predict SCLC chemotherapy resistance and clinical prognosis.