| Objective: Lung cancer is one of the most common malignant tumor. Itsmorbidity and mortality ranks are first in tumors worldwide, and it still hasan upward trend.The five-year survival rate of lung cancer is less than15%,and it is a serious threat to human health and life. The incidence of lungcancer in the age is usually above40years old,and its peak age of onset isbetween the ages of60to79years. The proportion of men and womensuffering from lung cancer is2.3:1.The75%cases of lung cancer is non-smallcell lung cancer (NSCLC), which includes squamous cell carcinoma,adenocarcinoma and large cell carcinoma. Small cell carcinoma accounts forabout25%. Environmental factors play a important role on the occurrence oflung cancer. Although the the pathogenesis of lung cancer are not fullyelucidated, but large number of studies have shown that its formation is amulti-factor, multi-stage process,and is the result of the role of theenvironment and other risk factors and genetic factors. In recent years, withthe development of molecular biology techniques, the people began to explorethe process of lung cancer at the molecular level. The study found that lungcancer is not only related to genes within the nucleus changes but alsoassociated with mtDNA mutations. Study of mtDNA mutations can learn moreabout lung cancer pathogenesis and development, and provide the basis andhelp for their diagnosis, treatment and prognosis.MtDNA is a long for16569bp double-stranded closed-loop molecule,andthe two chains are independent coding. MtDNA genome is divided into thecoding region and noncoding region (D-loop region). The coding regionencodes37genes. D-loop region is located in16026np-577np, accounting for about6%of all the mtDNA,and including three hypervariable region (HVR).Itis the replication initiation site and the only non-coding region of mtDNA,andplays an important regulatory role in mtDNA transcription and replication.Asgenetic material outside the nuclear, mtDNA has a very active self-replicatingability,and its replication, transcription and translation are all outside thenuclear. Due to the special structure of its own gene, and the lack of a sound,effective self-repair system, comparing with nDNA, mtDNA is moresusceptible to damage by various types of mutagens and produce mutation. Inrecent years, the lung cancer study found that there was high variability in themitochondrial DNAD-loop region. But there has no report on the relationshipof the mtDNA gene polymorphism and lung cancer prognosis. Thisexperiment studies the gene polymorphism of mtDNA16390A-G,16519T-Cand clinical features whether has a impact on the late (III/IV) non-small celllung cancer survival time or not. And it may provide a basis for predicting thesurvival time of advanced lung cancer.Methods: Collecting venous blood5ml from54cases of advancedNSCLC, treated in the Forth Hospital of He Bei Medical University,diagnosed by cytopathology or histopathology,and put them in tubescontaining EDTA and store at4℃. Extracting the WBC mtDNA by proteinaseK digestion-saturated sodium chloride salting out within a week after theblood was collected.Mading the D-loop District of mtDNA PCR amplificationby primer-introduced restriction analysis PCR. The amplification products wassent to Shanghai Biological Engineering Technology&Services Co. Ltd.andsequenced. The sequencing results was compared to Cambridge standards ofhuman mitochondrial DNA sequences (RACambridge sequence) to detect thegene polymorphism of mtDNA16390and mtDNA16519sites. Recording theclinical data and follow-up to observe their survival.Statistical analysis was performed using SPSS13.0software package(SPSS Company, Chicago, Illinois, USA). Kaplan–Meier method(ProductLimit method)was used to draw survival curves and its significance was testedby Log-Rank Test. Factors related to the prognosis were analyzed by the method of Cox Regression Analysis, and Calculatting the relative risk and its95%confidence interval.Results:1The occurrence rate of A polymorphism at mtDNA16390G/A loci is7.41%(4/54). C polymorphism has a occurrence rate of38.9%(21/54),which greater than10%.2The rate of follow-up visition was100%. The survival time of1to100monthes.The overall median survival time was16.00monthes,1-yearsurvival rate was62.96%,2-year survival rate was29.62%,5-year survivalrate was5.56%.3The median survival of patients with mtDNA16390sites carrying G and Abases, respectively, are17.00months and6.50months,and lung cancerpatients with G bases have a prolonged survival than those with A base(P<0.05,RR=3.793,95%CI:1.219-11.804).4The median survival of patients with mtDNA16519sites carrying T and Cbases, respectively, are20.00months and6.50months,and lung cancerpatients with T bases have a prolonged survival than those with C base(P<0.05,RR=1.826,95%CI:0.999-3.338).5The patients treated and untreated have a respectively median survival of16.50months and8.50months, and that the treated patients have aprolonged survival than untreated ones(P <0.05,RR=5.505,95%CI:1.238—24.467).6Gender, age, clinical stage, pathological type and smoking have nosignificant effect on lung cancer survival(P>0.05).Conclusion:1There are highly polymorphic at mtDNA16390gene loci and16519geneloci.2MtDNA16390G/A gene polymorphism has a influence on lung cancersurvival,and G base carriers have a significantly longer survival than the Abase carriers.3MtDNA16390T/C gene polymorphism has a influence on lung cancer survival,and T base carriers have a significantly longer survival than the Cbase carriers.4Treatment can significantly extend the lung cancer patient,s survival.5In this experiment, gender, age, clinical stage, pathological type, and smok-ing have no significant effect on the prognosis of lung cancer. |
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