引用本文:季晓磊,其其格,王泽鑫.肝细胞癌组织中miR-129-5p、CBX4的表达及临床意义[J].中国临床新医学,2025,18(4):402-407.
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肝细胞癌组织中miR-129-5p、CBX4的表达及临床意义
季晓磊1,其其格1,王泽鑫2
1.内蒙古医科大学附属医院感染科,呼和浩特 010010;2.内蒙古医科大学附属医院介入医学科,呼和浩特 010010
摘要:
[摘要] 目的 分析肝细胞癌(HCC)组织中miR-129-5p、色素框同源物4(CBX4)的表达及临床意义。方法 收集2018年8月至2021年8月内蒙古医科大学附属医院120例HCC患者的临床资料。通过生物信息学方法分析HCC组织和正常组织中CBX4蛋白水平以及miR-129-5p与CBX4靶向调控关系。取患者癌组织和癌旁组织(距离癌组织≥5 cm)标本。采用实时荧光定量聚合酶链反应(RT-qPCR)检测组织中miR-129-5p、CBX4 mRNA水平。根据癌组织中miR-129-5p水平的平均值将患者分为miR-129-5p低表达组和miR-129-5p高表达组。采用免疫组化染色法检测组织中CBX4蛋白表达情况。根据癌组织中CBX4蛋白表达情况将患者分为CBX4阳性表达组和CBX4阴性表达组。记录患者随访3年期间生存情况。采用Pearson相关分析癌组织中miR-129-5p与CBX4 mRNA水平的相关性。采用Kaplan-Meier法绘制生存曲线,组间比较采用log-rank检验。采用Cox回归分析影响HCC患者预后的因素。结果 生物信息学分析结果显示,HCC组织中CBX4蛋白水平显著高于正常组织(P<0.05),miR-129-5p与CBX4蛋白存在靶向调控关系。HCC患者癌组织中CBX4蛋白阳性表达率显著高于癌旁组织[65.00%(78/120)vs 24.17%(29/120), χ2=40.492,P<0.05)]。癌组织中miR-129-5p水平低于癌旁组织,CBX4 mRNA水平高于癌旁组织,差异有统计学意义(P<0.05)。癌组织中miR-129-5p水平与CBX4 mRNA水平呈负相关(r=-0.676,P<0.05)。miR-129-5p低表达组(<0.72)临床分期Ⅲ~Ⅳ期、肿瘤低分化、有血管侵犯的患者比例显著高于miR-129-5p高表达组(≥0.72)(P<0.05)。CBX4阳性表达组临床分期Ⅲ~Ⅳ期、肿瘤低分化、有血管侵犯的患者比例显著高于CBX4阴性表达组(P<0.05)。miR-129-5p高表达组的生存预后优于miR-129-5p低表达组(log-rank检验: χ2=19.048,P<0.001)。CBX4阴性表达组的生存预后优于CBX4阳性表达组(log-rank检验: χ2=11.977,P=0.001)。多因素Cox回归分析结果显示,miR-129-5p高表达是患者存活的独立保护因素(P<0.05),CBX4阳性表达、临床分期Ⅲ~Ⅳ期是患者发生死亡的独立危险因素(P<0.05)。结论 HCC组织中miR-129-5p水平降低,CBX4水平升高,二者与临床分期、肿瘤分化程度、血管侵犯及生存预后有关。
关键词:  肝细胞癌  miR-129-5p  色素框同源物4  临床病理特征  预后
DOI:10.3969/j.issn.1674-3806.2025.04.09
分类号:
基金项目:内蒙古自治区科技计划项目(编号:kjt12sf032)
Expressions of miR-129-5p and CBX4 in hepatocellular carcinoma tissues and their clinical significance
JI Xiaolei1, QI Qige1, WANG Zexin2
1.Department of Infectious Diseases, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010010, China; 2.Department of Interventional Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010010, China
Abstract:
[Abstract] Objective To analyze the expressions of miR-129-5p and chromobox homolog 4(CBX4) in hepatocellular carcinoma(HCC) tissues and their clinical significance. Methods The clinical data of 120 HCC patients were collected from the Affiliated Hospital of Inner Mongolia Medical University between August 2018 and August 2021. Bioinformatics method was used to analyze the CBX4 protein level in HCC tissues and normal tissues and the targeted regulatory relationship between miR-129-5p and CBX4. The cancerous tissues and their para-cancerous tissues(≥5 cm from the cancerous tissues) were collected from the patients. Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detect the levels of miR-129-5p and CBX4 mRNA in the tissues. According to the average level of miR-129-5p in the cancerous tissues, the patients were divided into low miR-129-5p expression group and high miR-129-5p expression group. The expression of CBX4 protein was detected by using immunohistochemical staining. According to the expressions of CBX4 protein in the cancerous tissues, the patients were divided into CBX4 positive expression group and CBX4 negative expression group. The survival of the patients during the follow-up period of 3 years was recorded. Pearson correlation was used to analyze the correlation between miR-129-5p and CBX4 mRNA level in the cancerous tissues. Kaplan-Meier method was used to plot the survival curves, and log-rank test was used for comparison between groups. Cox regression was used to analyze the prognostic factors of the HCC patients. Results The results of bioinformatics analysis showed that the level of CBX4 protein in the HCC tissues was significantly higher than that in the normal tissues(P<0.05), and there was a targeted regulatory relationship between miR-129-5p and CBX4 protein. The positive expression rate of CBX4 protein in the HCC patients′cancerous tissues was significantly higher than that in the HCC patients′ para-cancerous tissues[65.00%(78/120)vs 24.17%(29/120), χ2=40.492, P<0.05)]. The level of miR-129-5p in the cancerous tissues was lower than that in their para-cancerous tissues, while the level of CBX4 mRNA in the cancerous tissues was higher than that in their para-cancerous tissues, with statistically significant differences between the cancerous tissues and their para-cancerous tissues(P<0.05). There was a negative correlation between miR-129-5p level and CBX4 mRNA level in the cancerous tissues(r=-0.676, P<0.05). The proportion of the patients with clinical stages Ⅲ-Ⅳ, low tumor differentiation and vascular invasion in the low miR-129-5p expression group(<0.72) was significantly higher than that in the high miR-129-5p expression group(≥0.72)(P<0.05). The proportion of the patients with clinical stages Ⅲ-Ⅳ, low tumor differentiation and vascular invasion in the CBX4 positive expression group was significantly higher than that in the CBX4 negative expression group(P<0.05). The survival prognosis of the high miR-129-5p expression group was better than that of the low miR-129-5p expression group(log-rank test: χ2=19.048, P<0.001). The survival prognosis of the CBX4 negative expression group was better than that of the CBX4 positive expression group(log-rank test: χ2=11.977, P=0.001). The results of multivariate Cox regression analysis showed that high expression of miR-129-5p was an independent protective factor for the patients′ survival(P<0.05), while positive expression of CBX4 and clinical stages Ⅲ-Ⅳ were independent risk factors for the patients′ death(P<0.05). Conclusion The level of miR-129-5p decreases and the level of CBX4 increases in HCC tissues, which are related to clinical stage, degree of tumor differentiation, vascular invasion and survival prognosis.
Key words:  Hepatocellular carcinoma(HCC)  miR-129-5p  Chromobox homolog 4(CBX4)  Clinicopathological features  Prognosis