CAJ | 학술논문

目的：借助生物信息学工具探索上皮性卵巢癌多药耐药相关的生物学通路及SNP位点。方法从基因表达综合数据库的GSE13813芯片数据中筛选出初次术后经铂类和紫杉醇类联合化疗的73例患者，其中22例为化疗耐药，51例为化疗敏感。采用PLINK软件进行等位基因关联检验分析，对差异表达的SNP位点（P<0.05）采用WebGestalt在线工具和DAVID进行基因通路富集分析，并筛选与上皮性卵巢癌多药耐药相关的共同通路。利用SciMiner工具检索上皮性卵巢癌多药耐药研究相关基因，并用上述方法进行通路分析以交叉验证。最后对通路涉及的SNP及其连锁位点采用Snpfunc网站进行功能预计。结果敏感组和耐药组共有4978个差异表达的SNP位点。通路分析显示黏附分子、钙离子信号和ErbB 信号途径与上皮性卵巢癌多药耐药相关。其中ErbB 信号在文献挖掘通路分析中得到交叉验证。11个连锁SNP可通过异常剪接、编码非同义氨基酸等方式改变基因功能，从而影响通路在上皮性卵巢癌联合化疗中的作用。结论通过基因通路富集方法找到3个与上皮性卵巢癌多药耐药相关的通路及一批可能影响通路的功能性SNP位点。检测这些位点有助于预测上皮性卵巢癌联合化疗的反应。
목적：차조생물신식학공구탐색상피성란소암다약내약상관적생물학통로급SNP위점。방법종기인표체종합수거고적GSE13813심편수거중사선출초차술후경박류화자삼순류연합화료적73례환자，기중22례위화료내약，51례위화료민감。채용PLINK연건진행등위기인관련검험분석，대차이표체적SNP위점（P<0.05）채용WebGestalt재선공구화DAVID진행기인통로부집분석，병사선여상피성란소암다약내약상관적공동통로。이용SciMiner공구검색상피성란소암다약내약연구상관기인，병용상술방법진행통로분석이교차험증。최후대통로섭급적SNP급기련쇄위점채용Snpfunc망참진행공능예계。결과민감조화내약조공유4978개차이표체적SNP위점。통로분석현시점부분자、개리자신호화ErbB 신호도경여상피성란소암다약내약상관。기중ErbB 신호재문헌알굴통로분석중득도교차험증。11개련쇄SNP가통과이상전접、편마비동의안기산등방식개변기인공능，종이영향통로재상피성란소암연합화료중적작용。결론통과기인통로부집방법조도3개여상피성란소암다약내약상관적통로급일비가능영향통로적공능성SNP위점。검측저사위점유조우예측상피성란소암연합화료적반응。
Objective This bioinformatics study aimed to explore signaling pathways and functional single nucleotide polymorphisms (SNPs)related to multidrug resistance (MDR)in epithelial ovarian cancer. Methods Patients with ovarian cancer treated by platinum and paclitaxel after primary surgery were selected from the SNP array(GSE13813)in the Gene Expression Omnibus(GEO)dataset. PLINK software and allelic tests were applied to identify SNPs significantly related to MDR (P<0.05),which were further analyzed online using gene-set enrichment pathway analysis (GSEA)in WebGestalt and DAVID. SciMiner was used to search for all genes potentially related to MDR in patients with epithelial ovarian cancer,and the corresponding functional pathways were explored using WebGestalt and DAVID.Finally,the on-line software Snpfunc was used to predict functions of SNPs in MDR-related pathways as well as of their partners in linkage disequilibrium. Results GSEA of 4978 significant SNPs from 22 platinum-resistant and 51 platinum-sensitive patients identified cell adhesion molecules and calcium-and ErbB-dependent signaling pathways as being potentially related to MDR.Literature analysis supported the association between the ErbB signaling pathway and MDR.Function prediction suggested that 11 functional SNPs may modify gene function by causing aberrant splicing or amino acid substitutions,potentially affecting response to combination chemotherapy. Conclusion Using GSEA,we identified three possible MDR-related signaling pathways and 11 functional SNPs that may help predict responses to platinum-based combination chemotherapy for epithelian ovarian cancer. These findings should be confirmed in future studies.