Microarray Gene Expression Profiling For Identifying Different Responses To Radiotherapy And Chemoradiotherapy In Patients With Cervical Cancer

Cervical cancer is the second most common gynecologicalmalignancy after breast cancer and also the fourth leading cause of death from cancer in women[1,2].In 2012,there were approximately 528,000 women with cervical cancer and 266,000 deaths caused by the disease[2].About 80%of cervical cancer cases were in developing countries[3].Radiotherapy(RT)and chemoradiotherapy(CRT)are important therapeutic methods for patients with cervical cancer[4,5].There has been an increasing interest in the use of RT and CRT to treat cervical cancer over the last decade[6,7].RT brings similar survival outcomes for patients with cervical cancer as surgery,but with negative impacts,such as sexual function interruption[8].Cisplatin-based CRT is the standard modality of care for patients in advanced stages[9].It is reported that the therapeutic effect of cisplatin-based CRT is better than that of RT[10].Advantages of CRT over RT in patients with cervical cancer have now been well demonstrated in a series of randomized prospective trials[11];for instance,absolute improvement in the overall survival and significant reduction in local recurrence[12,13].However,few studies have investigated the genetic response to these two therapies.In this study,the authors investigated the microarray expression data of patients with cervical cancer that underwent RT and CRT treatment to analyze the molecular mechanism underlying CRT.Differentially expressed genes(DEGs)between RT and CRT treatment were identified and their underlying functions were predicted.Subsequently,the protein-protein interaction(PPI)network,transcription factor(TF)-DEG network,and miRNA-DEG network were constructed to identify key molecules during CRT treatment..Purpose:Cervical cancer,which is treated by radiotherapy(RT)and chemoradiotherapy(CRT),has high morbidity and mortality in women.This study aimed to identify differences in gene response to CRT and RT..Method:GSE3578 was downloaded from Gene Expression Omnibus including specimens from 20 RT-treated patients and 19 CRT-treated patients.Differentially expressed genes(DEGs)were identified using siggenes package in R.Protein-protein interaction(PPI)network was visualized by cytoscape.MCODE and cytoscape was used separately to mine and construct modules in the PPI network.Transcription factor(TF)-DEG and miRNA-DEG pairs were predicted and then visualized by cytoscape.Result:Total 22 upregulated and 181 downregulated genes were identified in CRT samples.Several functions were enriched for these DEGs.A module involving ZNF449 and ZNF673 was mined from the PPI network of downregulated genes.In the TF-DEG regulatory networks,downregulated GATA3(which was modulated by SP1)was also a TF,as well as upregulated CDK6 was regulated by several TFs(e.g.GATA3).Hsa-miR-17,hsa-miR-34a,hsa-miR-124,hsamiR-1185-2-3p,hsa-1185-1-3p,and hsa-let-7f-2-3p were identified as key miRNAs in the miRNA-DEG regulatory network.Conclusion:CRT might cure cervical cancer by acting on those molecules that were more sensitive to CRT than CT.