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中华乳腺病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (04) : 198 -205. doi: 10.3877/cma.j.issn.1674-0807.2025.04.002

论著

三阴性乳腺癌组织长链非编码RNA CCAT1、miR-152表达与增殖侵袭基因以及临床病理特征的关系
卜烨(), 王鹏, 安丽颖, 陈园   
  1. 072750 保定,保定市第二中心医院普外科
  • 收稿日期:2024-12-10 出版日期:2025-08-01
  • 通信作者: 卜烨
  • 基金资助:
    2022年度河北省医学科学研究课题计划资助项目(20220279)

Relationship between long non-coding RNA CCAT1,miR-152 expression and proliferation/invasion genes and clinicopathological characteristics in triple negative breast cancer tissues

Ye Bu(), Peng Wang, Liying An, Yuan Chen   

  1. Department of General Surgery, Baoding Second Central Hospital, Baoding 072750, China
  • Received:2024-12-10 Published:2025-08-01
  • Corresponding author: Ye Bu
引用本文:

卜烨, 王鹏, 安丽颖, 陈园. 三阴性乳腺癌组织长链非编码RNA CCAT1、miR-152表达与增殖侵袭基因以及临床病理特征的关系[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(04): 198-205.

Ye Bu, Peng Wang, Liying An, Yuan Chen. Relationship between long non-coding RNA CCAT1,miR-152 expression and proliferation/invasion genes and clinicopathological characteristics in triple negative breast cancer tissues[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2025, 19(04): 198-205.

目的

探讨三阴性乳腺癌(TNBC)组织中长链非编码RNA结肠癌相关转录本1(lncRNA CCAT1)、微小RNA-152(miR-152)表达与增殖基因、侵袭基因表达和临床病理特征的关系。

方法

收集2021年7月至2024年6月保定市第二中心医院手术切除的TNBC组织及对应癌旁组织标本120例,采用实时荧光定量PCR检测组织中lncRNA CCAT1、miR-152、增殖基因(EZH2、PIWIL2、YAP1)、侵袭基因(GLI1、TUG1、RAB11)表达。通过StarBase数据库预测lncRNA CCAT1与miR-152的结合位点。使用Pearson相关分析探讨TNBC组织中 lncRNA CCAT1、miR-152 表达水平与增殖、侵袭相关基因表达水平之间的相关性。正态分布的计量资料两组间比较采用独立样本t检验,与癌旁组织比较采用配对t检验,多组间比较采用方差分析。逐步多元线性回归分析TNBC组织lncRNA CCAT1、miR-152表达与增殖基因、侵袭基因和临床病理特征的关系。

结果

与癌旁组织相比较,TNBC组织中lncRNA CCAT1、EZH2、PIWIL2、YAP1、GLI1、TUG1、RAB11的mRNA表达水平升高,miR-152表达降低(P均<0.001)。lncRNA CCAT1与miR-152存在结合位点,并且与miR-152表达呈负相关(r=-0.761,P<0.001)。lncRNA CCAT1的表达与EZH2、PIWIL2、YAP1、GLI1、TUG1、RAB11的mRNA表达水平呈正相关(r=0.716、0.685、0.702、0.734、0.726、0.688,P均<0.001),miR-152表达与EZH2、PIWIL2、YAP1、GLI1、TUG1、RAB11的mRNA表达水平呈负相关(r=-0.713、-0.702、-0.698、-0.721、-0.716、-0.703,P均<0.001)。肿瘤直径>2 cm、组织学3级、TNM分期Ⅲ期、有淋巴结转移TNBC组织中lncRNA CCAT1表达更高,miR-152的表达更低(与肿瘤直径≤2 cm、组织学1~2级、TNM分期Ⅰ~Ⅱ期、无淋巴结转移者比较(t=2.529、F=20.827、t=2.944、3.172,P=0.013、<0.001、0.004、0.002;t=-2.481、F=-10.611、t=-2.936、-3.160,P=0.015、<0.001、0.005、0.002)。TNBC组织lncRNA CCAT1表达水平与EZH2、PIWIL2、YAP1、GLI1、TUG1、RAB11的mRNA表达以及肿瘤直径、组织学分级、TNM分期和淋巴结转移状态呈显著正相关(OR=3.203、2.807、2.034、4.425、4.476、2.185、2.074、3.127、2.255、4.972,P=0.002、0.006、0.044、<0.001、<0.001、0.031、0.040、0.002、0.026、<0.001);而miR-152表达水平与上述变量呈显著负相关(OR=-2.543、-2.787、-2.120、-2.856、-3.498、-2.403、-2.225、-3.200、-2.819、-4.284,P=0.012、0.006、0.036、0.005、0.001、0.018、0.028、0.002、0.006、<0.001)。

结论

TNBC组织lncRNA CCAT1呈高表达,miR-152呈低表达,与TNBC增殖、侵袭能力增强和不良临床病理参数密切相关,可能成为评价TNBC恶性进展的生物标志物。

Objective

To explore the relationship between long non-coding RNA colon cancer related transcript 1 (lncRNA CCAT1),microRNA-152 (miR-152) expression and proliferation/invasion genes expression and clinicopathological characteristics in triple negative breast cancer (TNBC).

Methods

A total of 120 TNBC tissue samples and paired adjacent normal tissue samples were collected from surgical resections performed in the Baoding Second Central Hospital from July 2021 to June 2024. The expression levels of lncRNA CCAT1,miR-152 and proliferation-related genes (EZH2,PIWIL2,YAP1),as well as invasion-related genes (GLI1,TUG1,RAB11),were detected using real-time quantitative PCR. Binding sites between lncRNA CCAT1 and miR-152 were predicted using the StarBase database. Pearson correlation was used to analyze correlations between the expression levels of lncRNA CCAT1,miR-152 and the expression levels of proliferation and invasion related genes in TNBC tissues. For normally distributed measurement data, an independent samples t-test was used for comparisons between two groups, analysis of variance for comparisons among multiple groups and paired t-test was used for comparisons with adjacent non-tumor tissues. The relationship between the expression of lncRNA CCAT1 and miR-152 in TNBC tissue and proliferation genes,invasion genes and clinical pathological characteristics were analyzed by stepwise multiple linear regression.

Results

Compared with adjacent normal tissues,TNBC tissues exhibited significantly higher expression levels of lncRNA CCAT1,EZH2 mRNA,PIWIL2 mRNA,YAP1 mRNA,GLI1 mRNA,TUG1 mRNA,and RAB11 mRNA,while miR-152 expression was significantly decreased (all P<0.001). Binding sites between lncRNA CCAT1 and miR-152 were identified,and their expression levels in TNBC tissues showed a negative correlation (r=-0.761,P<0.001). Pearson correlation analysis revealed that lncRNA CCAT1 expression was positively correlated with the mRNA expression of EZH2,PIWIL2,YAP1,GLI1,TUG1,and RAB11 (r=0.716,0.685,0.702,0.734,0.726,0.688; all P<0.001),whereas miR-152 expression was negatively correlated with the mRNA expression of these genes (r=-0.713,-0.702,-0.698,-0.721,-0.716,-0.703; all P<0.001). The expression levels of lncRNA CCAT1 in TNBC tissues with tumor diameter >2 cm,histological grade 3,TNM stage Ⅲ and lymph node metastasis were significantly higher than that with tumor diameter ≤2 cm,histological grade 1–2,TNM stage Ⅰ–Ⅱ and no lymph node metastasis (t=2.529,F=20.827,t=2.944,t=3.172; P=0.013,<0.001,0.004,0.002),the expression levels of miR-152 were significantly lower than that with tumor diameter ≤2 cm,histological grade Ⅰ/Ⅱ,TNM stage Ⅰ–Ⅱ and no lymph node metastasis (t=-2.481,F=-10.611,t=-2.936,t=-3.160; P=0.015,<0.001,0.005,0.002). The expression level of lncRNA CCAT1 in TNBC tissue were positively correlated with the mRNA expression of EZH2,PIWIL2,YAP1,GLI1,TUG1,RAB11,as well as tumor diameter,histological grade,TNM staging and lymph node metastasis status (OR=3.203,2.807,2.034,4.425,4.476,2.185,2.074,3.127,2.255,4.972; P=0.002,0.006,0.044,<0.001,<0.001,0.031,0.040,0.002,0.026,<0.001). The expression level of miR-152 were negatively correlated with the gene expression and clinical pathological indicators mentioned above (OR=-2.543,-2.787,-2.120,-2.856,-3.498,-2.403,-2.225,-3.200,-2.819,-4.284; P=0.012,0.006,0.036,0.005,0.001,0.018,0.028,0.002,0.006,<0.001).

Conclusion

lncRNA CCAT1 is highly expressed and miR-152 is lowly expressed in TNBC tissues,which are closely related to the enhanced proliferation,invasion ability of TNBC cells and poor clinicopathological characteristics of patients,and may become a biomarker for evaluating the malignant progression of TNBC.

表1 PCR引物序列
表2 120例TNBC及癌旁组织中lncRNA CCAT1和miR-152表达比较(
图1 lncRNA CCAT1与miR-152的结合位点 注:lncRNA为长链非编码RNA;miR-152为微小RNA152
图2 120例TNBC组织中lncRNA CCAT1与miR-152表达的线性散点图 注:r=-0.761,P<0.001;lncRNA CCAT1为长链非编码RNA CCAT1;miR-152为微小RNA152
表3 120例TNBC及癌旁组织增殖基因和侵袭基因的mRNA表达比较(
表4 120例TNBC组织lncRNA CCAT1、miR-152表达与增殖基因和侵袭基因的相关性
表5 120例TNBC中lncRNA CCAT1、miR-152表达与临床病理特征的关系(
表6 多元线性回归分析的变量赋值表
表7 120例TNBC组织lncRNA CCAT1表达与增殖基因、侵袭基因和临床病理参数的逐步多元线性回归分析
表8 120例TNBC组织miR-152表达与增殖基因、侵袭基因和临床病理参数的逐步多元线性回归分析
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