MYLIP和miR-542-3p与宫颈癌患者早期诊断及临床预后的关系

The relationship between MYLIP and miR-542-3p with early diagnosis and clinical prognosis in patients with cervical cancer

摘要

目的 探讨血清肌球蛋白调节轻链相互作用蛋白(MYLIP)和微小RNA-542-3p(miR-542-3p)表达水平对宫颈癌(CC)早期诊断价值及与其临床预后的关系。方法 选取本院2018年5月至2020年5月期间收治的128例CC患者作为CC组,另选取同期于本院就诊的86例宫颈上皮瘤变(CIN)患者作为CIN组,行体检的74例体检健康者作为对照组.采用实时荧光定量逆转录聚合酶链反应(qRT-PCR)法检测各组血清MYLIP mRNA和miR-542-3p表达水平,收集CC患者临床病理特征资料,分析二者表达水平与CC患者临床病理特征的关系;使用ENCORI网站预测MYLIP和miR-542-3p之间是否存在靶向关系;使用Pearson法分析MYLIP mRNA和miR-542-3p表达的相关性;绘制受试者工作特征(ROC)曲线评估MYLIP mRNA和miR-542-3p表达水平对CC的早期诊断价值;使用Kaplan-Meier法分析血清MYLIP mRNA和miR-542-3p表达水平与CC患者预后的关系;使用Cox回归分析影响CC患者预后的风险因素。结果 CC组血清MYLIP mRNA表达水平显著高于CIN组和对照组(F=118.850,P<0.001),CC组血清miR-542-3p表达水平显著低于CIN组和对照组(F=85.413,P<0.001);CC患者血清MYLIP mRNA和miR-542-3p表达水平与是否绝经(χ²=5.026、6.133)、宫颈浸润深度(χ²=6.767、7.957)、FIGO分期(χ²=7.788、11.480)、TNM分期(χ²=12.426、20.150)、淋巴结是否转移(χ²=8.821、12.687)有关(P<0.05);MYLIP和miR-542-3p存在靶向结合位点,且CC患者血清MYLIP mRNA与miR-542-3p表达为负相关关系(r=-0.415,P<0.001);血清MYLIP mRNA和miR-542-3p表达水平单独及联合诊断CC的曲线下面积(AUC)分别为0.807、0.815、0.894,联合诊断效果优于单独诊断(Z_{二者联合-MYLIP}=2.165、P=0.030;Z_{二者联合-miR-542-3p}=2.360,P=0.018);血清MYLIP mRNA高表达患者3年生存率显著低于低表达患者(52.24% vs. 78.69%,χ²=10.869,P=0.001),血清miR-542-3p高表达患者3年生存率显著高于低表达患者(79.03% vs. 51.52%,χ²=11.771,P=0.001);MYLIP mRNA高表达(HR=1.972,95%CI:1.565~2.485)是CC患者死亡的危险因素,miR-542-3p高表达(HR=0.517,95%CI:0.399~0.670)是CC患者死亡的保护因素(P<0.05)。结论 血清MYLIP mRNA和miR-542-3p表达水平对早期诊断宫颈癌具有一定的价值,且二者表达水平与宫颈癌患者临床预后密切相关.

Abstract

Objective To investigate the value of serum myosin regulatory light chain interacting protein (MYLIP) and microRNA-542-3p (miR-542-3p) expression levels in the early diagnosis of cervical cancer (CC) and their relationship with clinical prognosis. Methods A total of 128 patients with CC admitted to our hospital from May 2018 to May 2020 were selected as the CC group, 86 patients with cervical intraepithelial neoplasia (CIN) who were treated in our hospital during the same period were selected as the CIN group, and 74 healthy patients who underwent physical examination were selected as the control group. The expression levels of serum MYLIP mRNA and miR-542-3p in each group were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the clinicopathological characteristics of CC patients were collected, and the relationship between the expression levels and the clinicopathological characteristics of CC patients was analyzed. The ENCORI website was used to predict whether there was a targeting relationship between MYLIP and miR-542-3p; Pearson method was applied to analyze the correlation between MYLIP mRNA and miR-542-3p expression; the receiver operating characteristic (ROC) curve was plotted to evaluate the value of MYLIP mRNA and miR-542-3p expression levels in the early diagnosis of CC; the Kaplan-Meier method was applied to analyze the relationship between serum MYLIP mRNA and miR-542-3p expression levels and the prognosis of CC patients; Cox regression was used to analyze the risk factors affecting the prognosis and mortality in patients with CC. Results The expression level of serum MYLIP mRNA in CC group was significantly higher than that in CIN group and the control group (F=118.850, P<0.001), and the expression level of miR-542-3p was significantly lower than that in CIN group and the control group (F=85.413, P<0.001). The expression levels of serum MYLIP mRNA and miR-542-3p in CC patients were correlated with menopause (χ ²=5.026, 6.133), depth of cervical infiltration (χ²=6.767, 7.957), FIGO stage (χ²=7.788, 11.480), TNM stage (χ²=12.426, 20.150), and lymph node metastasis (χ²=8.821, 12.687) (P<0.05); there were targeted binding sites between MYLIP and miR-542-3p, and serum MYLIP mRNA was negatively correlated with miR-542-3p expression in CC patients (r=-0.415, P<0.001). The AUC of serum MYLIP mRNA and miR-542-3p expression levels individually and in combination in the diagnosis of CC were 0.807, 0.815, and 0.894, the combined diagnosis effect was better than that of individual diagnosis (Z_{the two are combined -MYLIP}=2.165, P=0.030; Z_{the two are combined -miR-542-3p}=2.360, P=0.018). The 3-year survival rate of patients with high expression of serum MYLIP mRNA was significantly lower than that of patients with low expression (52.24% vs. 78.69%, χ²=10.869, P=0.001), and the 3-year survival rate of patients with high expression of serum miR-542-3p was significantly higher than that of patients with low expression (79.03% vs. 51.52%, χ²=11.771, P=0.001). High expression of MYLIP mRNA is a risk factor for death in CC patients (HR=1.972, 95%CI: 1.565-2.485), and high expression of miR-542-3p is a protective factor for death in CC patients (HR=0.517, 95%CI: 0.399-0.670) (P<0.05). Conclusion The expression levels of serum MYLIP mRNA and miR-542-3p have certain value in the early diagnosis of cervical cancer, and their expression levels are closely related to the clinical prognosis of cervical cancer patients.

关键词

肌球蛋白调节轻链相互作用蛋白 / 微小RNA-542-3p / 宫颈癌 / 早期诊断 / 临床预后

Key words

myosin regulatory light chain interacting protein / microRNA-542-3p / cervical cancer / early diagnosis / clinical prognosis

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基金资助

河北省保定市科技计划项目(2241ZF195)