A Preliminary Study Of MicroRNA Expression Profile In Central And Peripheral Type Small-cell Lung Cancer

Objective:The biological behavior of small cell lung cancer is relatively poor,with the characteristics of short doubling time,early metastasis and high recurrence and chemoradiotherapy sensitivity.At present,chemotherapy is the main treatment for SCLC patients, but the major of patients would be local recurrence or distant metastasis in 1-2 years after first-line treatment.MicroRNAs are a family of evolutionarily conserved non-coding small RNA which post-transcriptionally regulate gene expression by binding specific mRNA.MiRNAs’functions include a range of bioprocess,such as cell proliferation, differentiation, apoptosis and immunity. Recent studys have reported that miRNAs could have play an important role in the occurrence and development of SCLC. In our study,we collected clinical data to observe clinical efficacy and prognosis of first-line chemotherapy in central and peripheral type extensive stage small cell lung cancer, then screened differentially expressed miRNAs by using microRNA microarray.The purpose of this study is to reasech the difference inherent mechanism between central and peripheral type SCLC from the aspect of microRNA,look for possible therapeutic target and provide theoretical basis for clinical treatment.Methods:Clinical data about 122 patients from Jan 2010 to Jan 2014 whose diagnoses were extensive stage small cell lung cancer were retrospectively analyzed.They all received etoposide and cispatin(EC) or etoposide and carboplatin(EP) first-line chemotherapy in our hospital. According to the different medical imaging performance,the patients were divided into central type group and peripheral type group.The effective rate and survival rate were calculated.Central type (n=5) and peripheral type (n=5) SCLC tissue samples from Jan 2013 to Dec 2014 were collected for this study.And we find 2 normal lung tissues as control group.Detect microRNA expression profile by using human Affymetrix microRNA testing chip 4.0 produced by Affymetrix company,and analysis the datas by using gene analysis software in order to obtain difference expressed microRNA in two groups.Result:There was no statistical significance in response rate after first-line chemotherapy(78.2%vs73.6%, P=0.57) and disease contral rate(87.0% vs89.5%, P=0.67)after first-line chemotherapy.There was no statistical significance in progression-free survival after first-line chemotherapy(8.0mvs5.3m, P=0.46).The overall survival of peripheral type group was better than that of central type group in delayed phase(18.5mvs 12.9m, P=0.00).All the total RNA extracted from FFPE tissues reached the standard quanlity.We discovered the expression of 105 kinds of miRNA obviously changed in central type SCLC compared with normal tissues,120 kinds of miRNA obviously changed in peripheral type SCLC compared with normal tissues.And 30 kinds of miRNA obviously changed in central type SCLC compared with peripheral type SCLC.And 20 of them significantly upregulated,10 of them downregulated.Meanwhile,20 of them have been reported in other studys,10 of them are newly detected in this study(miR-4736、miR-3679-3p、miR-4505、miR-4551、miR-4498. miR-6877-5p、 miR-6792-5p、miR-6861-5p、miR-6875-5p、miR-6746-5p).Conclusion:There were no significant difference in response rate and progression free survival between two groups,while the overall survival of patients in peripheral type group is better than in central type group.MicroRNA difference expressed in central type SCLC tissues compared with peripheral type SCLC tissues,and it’s hopeful to find new targets for SCLC target therapy in further study.