Zhu Y, Huang J M, Zhang G N, Li J M, Huang Jianmei
Department of Ultrasound, Sichuan Cancer Hospital, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.
Sichuan Cancer Institute, Chengdu 610041, China.
Zhonghua Fu Chan Ke Za Zhi. 2022 Feb 25;57(2):117-124. doi: 10.3760/cma.j.cn112141-20211025-00619.
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). 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. (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 <0.01); Pearson's correlation coefficient showed that the expression of lnc-MyD88 and MyD88 mRNA in EOC was positively correlated (=0.610, <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 <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 >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 <0.05), ascites cancer cells were the risk factors that significantly affected PFS in EOC patients (=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 <0.05), the size of residual lesions after surgery was an independent factor affecting PFS in EOC patients (=0.001). 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.
探讨长链非编码RNA-髓样分化因子88(lnc-MyD88)的表达及其与上皮性卵巢癌(EOC)患者预后的关系。选取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及铂类药物联合紫杉醇化疗6至8个疗程的70例EOC患者,收集新鲜癌组织标本。另外,收集同期因妇科良性疾病行手术治疗患者的28例新鲜正常卵巢组织作为对照组。采用逆转录(RT)及实时定量聚合酶链反应(qPCR)检测EOC组织及正常卵巢组织中lnc-MyD88及髓样分化因子88(MyD88)mRNA的表达。通过Pearson相关系数分析EOC中lnc-MyD88与MyD88 mRNA表达的相关性。分析lnc-MyD88表达与EOC患者临床病理特征的关系。采用Kaplan-Meier法计算患者生存率。采用log-rank检验进行单因素生存分析,采用Cox比例风险模型进行多因素生存分析。(1)RT-qPCR结果显示,EOC中lnc-MyD88及MyD88 mRNA的相对表达水平分别为0.009(0.000 - 0.049)和0.001(0.000 - 0.006),均显著高于正常卵巢组织(均<0.01);Pearson相关系数显示,EOC中lnc-MyD88与MyD88 mRNA表达呈正相关(r = 0.610,P < 0.01)。(2)lnc-MyD88在有淋巴结转移、远处转移及化疗耐药的EOC患者中的高表达率(分别为71%、64%和70%)显著高于对照组患者(分别为41%、40%和35%;均<0.05)。lnc-MyD88在不同年龄、病理类型、病理分级、手术病理分期、术后残留病灶大小及腹水癌细胞的EOC患者中的高表达率差异均无统计学意义(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、术后残留肿瘤大小以及lnc-MyD88和MyD88 mRNA的高表达均显著影响EOC患者的无进展生存期(PFS)和总生存期(OS)(均<0.05),腹水癌细胞是显著影响EOC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的高表达是影响EOC患者PFS和OS的独立因素(均<0.05),术后残留病灶大小是影响EOC患者PFS的独立因素(P = 0.001)。卵巢癌组织中lnc-MyD88表达水平显著升高。Lnc-MyD88作为EOC预后不良的分子标志物,与EOC中MyD88的表达相关,可能参与其表达调控,进而影响EOC患者的生存及预后。