Objective: To explore the expression of long non-coding RNA-myeloid differentiation factor 88 (lnc-MyD88) and its relationship with the prognosis of patients with epithelial ovarian cancer (EOC). Methods: A total of 70 EOC patients who underwent initial cytoreductive surgery and platinum-based drugs combined with paclitaxel for 6 to 8 courses were selected at Sichuan Cancer Hospital from January 2016 to January 2019. The fresh cancer tissue specimens were collected. In addition, 28 fresh normal ovarian tissues from patients who underwent surgery for benign gynecological diseases during the same period were collected as control group. Reverse transcription (RT) and real-time quantitative polymerase chain reaction (qPCR) were used to detect the expression of lnc-MyD88 and myeloid differentiation factor 88 (MyD88) mRNA in EOC tissues and normal ovarian tissues. The correlation between the expression of lnc-MyD88 and MyD88 mRNA in EOC was analyzed by Pearson's correlation coefficient. The relationship between lnc-MyD88 expression and clinicopathological characteristics of patients with EOC was analyzed. Kaplan-Meier method was used to calculate the survival rate of patients. The log-rank test was used for univariate survival analysis, and Cox proportional hazard model was used for multivariate survival analysis. Results: (1) RT-qPCR showed that the relative expression level of lnc-MyD88 and MyD88 mRNA in EOC were 0.009 (0.000-0.049) and 0.001 (0.000-0.006), respectively, which were significantly higher than those of normal ovarian tissues (all P<0.01); Pearson's correlation coefficient showed that the expression of lnc-MyD88 and MyD88 mRNA in EOC was positively correlated (r2=0.610, P<0.01). (2) The high expression rate of lnc-MyD88 in EOC patients with lymph node metastasis, distant metastasis and chemotherapy resistance (71%, 64% and 70%, respectively) were significantly higher than the patients in control group (41%, 40% and 35%, respectively; all P<0.05). There were no statistically significant in the high expression rate of lnc-MyD88 in EOC patients with different ages, pathological types, pathological grades, surgical pathological stages, postoperative residual lesion size, and ascites cancer cells (all P>0.05). (3) Univariate analysis showed that surgical pathological staging, lymph node metastasis, distant metastasis, postoperative residual tumor size, and high expression of lnc-MyD88 and MyD88 mRNA significantly affected the progression-free survival (PFS) and overall survival (OS) of EOC patients (all P<0.05), ascites cancer cells were the risk factors that significantly affected PFS in EOC patients (P=0.040); multivariate analysis showed that surgical pathological staging and high expression of lnc-MyD88 and MyD88 mRNA were independent factors affecting PFS and OS in EOC patients (all P<0.05), the size of residual lesions after surgery was an independent factor affecting PFS in EOC patients (P=0.001). Conclusions: The level of lnc-MyD88 expression in ovarian cancer tissues was significantly increased. Lnc-MyD88, as a molecular marker for the poor prognosis of EOC, is related to the expression of MyD88 in EOC, and may be involved in its expression regulation, thereby affecting the survival and prognosis of EOC patients.
目的： 探讨长链非编码RNA-髓样细胞分化因子88（lnc-MyD88）在卵巢上皮性癌（卵巢癌）组织中的表达及其与患者预后的关系。 方法： 选择2016年1月至2019年1月在四川省肿瘤医院接受初次肿瘤细胞减灭术且术后辅以铂类药物+紫杉醇方案化疗6~8个疗程的卵巢癌患者共70例，收集其新鲜癌组织标本；另收集同期28例因妇科良性疾病行手术治疗患者的新鲜正常卵巢组织标本作为对照。采用逆转录（RT）-实时荧光定量PCR（qPCR）技术检测卵巢癌和正常卵巢组织中lnc-MyD88、髓样细胞分化因子88（MyD88）mRNA的表达，并采用Pearson相关法分析卵巢癌组织中lnc-MyD88与MyD88 mRNA表达的相关性；分析lnc-MyD88表达与卵巢癌患者临床病理特征的关系；采用Kaplan-Meier法计算卵巢癌患者的生存率，单因素生存分析采用log-rank检验，多因素生存分析采用Cox比例风险模型。 结果： （1）RT-qPCR技术检测显示，卵巢癌组织中lnc-MyD88、MyD88 mRNA的中位表达水平分别为0.009（0.000~0.049）、0.001（0.000~0.006），均显著高于正常卵巢组织［分别为0.000（0.000~0.000）、0.000（0.000~0.001）；P均<0.01］。Pearson相关法分析显示，卵巢癌组织中lnc-MyD88与MyD88 mRNA的表达水平呈显著正相关（r2=0.610，P<0.01）。（2）有淋巴结转移、远处转移、化疗耐药的卵巢癌患者的lnc-MyD88高表达率（分别为71%、64%、70%）显著高于无淋巴结转移、远处转移、化疗耐药者（分别为41%、40%、35%；P均<0.05）；而不同年龄、病理类型、病理分级、手术病理分期、术后残留灶大小以及腹水有无癌细胞的卵巢癌患者的lnc-MyD88高表达率分别比较，差异则均无统计学意义（P均>0.05）。（3）单因素分析显示，手术病理分期、淋巴结转移、远处转移、术后残留灶大小以及lnc-MyD88和MyD88 mRNA高表达均为显著影响卵巢癌患者无进展生存时间（PFS）和总生存时间（OS）的危险因素（P均<0.05），腹水有癌细胞为显著影响卵巢癌患者PFS的危险因素（P=0.040）；多因素分析显示，手术病理分期以及lnc-MyD88和MyD88 mRNA高表达均为影响卵巢癌患者PFS和OS的独立因素（P均<0.05），术后残留灶大小为影响卵巢癌患者PFS的独立因素（P=0.001）。 结论： 卵巢癌组织中lnc-MyD88的表达水平显著增高，且lnc-MyD88与MyD88 mRNA表达呈正相关关系，lnc-MyD88可能参与MyD88基因表达的调控，从而影响卵巢癌患者的预后，有望作为预测卵巢癌不良预后的分子标志物。.