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目的卵巢癌是女性生殖器官常见的恶性肿瘤之一,90%的卵巢癌患者诊断时已进展到晚期(Ⅲ/Ⅳ期)。尽管治疗方式的不断改进,但晚期卵巢癌患者5年总生存率为20%,而早期卵巢癌患者5年总生存率>90%。本研究旨在识别卵巢癌脂质组学诊断生物标志物,提高卵巢癌早期诊断的准确性。方法采用稀疏组lasso变量筛选方法和单因素分析相结合的方法,对2011-03-01-2013-07-31哈尔滨医科大学附属肿瘤医院的139例卵巢癌患者和76例对照患者的血浆脂质组学数据进行分析,筛选可用于诊断卵巢癌脂质组学的生物标志物,在差异代谢物中选择与CA125相关性小的物质作为最终诊断标志物,通过七折交叉验证方法来评价其预测效果及与CA125联合的诊断准确性。进一步采用cytoscape软件研究差异脂质物质间的相互作用。通过Wilcoxon秩和检验方法筛选出能够区分早晚期卵巢癌的生物标志物。结果共筛选出20种可用于区分卵巢癌和对照的差异脂质生物标志物,其中Stearamide、Stearic acid、Arachidic acid和PI(42∶9)与CA125不相关(P<0.05),这4个脂质与CA125联合AUC值为0.94,大于CA125单独的诊断性能。另外,其中8个差异脂质在早期与晚期上皮性卵巢癌患者中有差异,分别为PC(35∶4)、PC(38∶6)、PC(46∶4)、PC(P-35∶2)、PE(P-36∶6)、PG(34∶2)、Cer(d18∶1/16∶0)和3-Deoxyvitamin D3,均P值<0.05。结论卵巢癌血浆脂质组学筛选出的物质提高了CA125单独诊断的准确性,其中8个差异物质可以作为卵巢癌早期诊断潜在的生物标志物。
Objective Ovarian cancer is one of the most common malignant tumors in female genital organs. More than 90% of ovarian cancer patients have advanced to the advanced stage (stage Ⅲ / Ⅳ). Despite a continuous improvement in treatment, the 5-year overall survival for patients with advanced ovarian cancer is 20%, whereas the 5-year overall survival for patients with early-stage ovarian cancer is> 90%. The purpose of this study was to identify lipidomic biomarkers for ovarian cancer and to improve the accuracy of early diagnosis of ovarian cancer. Methods A combination of sparse group lasso variable screening method and univariate analysis was used to analyze the plasma lipids in 139 ovarian cancer patients and 76 control patients at Affiliated Tumor Hospital of Harbin Medical University from March 2011 to January 2013. The biomarkers that can be used to diagnose ovarian cancer lipidomics were screened by panel data, and those with low correlation with CA125 were selected as the final diagnostic markers for differential metabolites, and their predictions were evaluated by a seven-fold cross-validation Efficacy and diagnostic accuracy associated with CA125. Cytoscape software was further used to study the interactions between the different lipid substances. Wilcoxon rank sum test was used to screen out biomarkers that distinguish early and late ovarian cancers. RESULTS: Twenty different lipid biomarkers were screened for differentiation between ovarian cancer and controls. Stearamide, Stearic acid, Arachidic acid and PI (42:9) were not associated with CA125 (P <0.05). These four lipids AUC value of 0.94 was associated with CA125, which was greater than the diagnostic performance of CA125 alone. In addition, eight of these differentiated lipids differed in patients with early-stage and advanced-stage epithelial ovarian cancer and were PC (35:4), PC (38:6), PC (46: 4), PC 2), PE (P-36: 6), PG (34: 2), Cer (d18: 1/16: 0) and 3-Deoxyvitamin D3. Conclusions The plasma lipidomics screening of ovarian cancer can improve the accuracy of single diagnosis of CA125, of which 8 differential substances can be used as potential biomarkers for the early diagnosis of ovarian cancer.