[1]刘 伶,邹世芳,巩 亮,等.血浆外泌体LncRNA BLACAT1 和E-cadherin mRNA 表达水平对乳腺癌早期诊断的价值研究[J].现代检验医学杂志,2022,37(05):70-75.[doi:10.3969/j.issn.1671-7414.2022.05.015]
　LIU Ling,ZOU Shi-fang,GONG Liang,et al.Value of Plasma Exosomes LncRNA BLACAT1 and Ecadherin mRNA Expression in Early Diagnosis of Breast Cancer[J].Journal of Modern Laboratory Medicine,2022,37(05):70-75.[doi:10.3969/j.issn.1671-7414.2022.05.015]
点击复制

血浆外泌体LncRNA BLACAT1 和E-cadherin mRNA 表达水平对乳腺癌早期诊断的价值研究()
分享到：

《现代检验医学杂志》[ISSN:/CN:]

卷:
第37卷
期数:
2022年05期
页码:
70-75
栏目:
论著
出版日期:
2022-09-15

文章信息/Info

Title:
Value of Plasma Exosomes LncRNA BLACAT1 and Ecadherin mRNA Expression in Early Diagnosis of Breast Cancer
文章编号:
1671-7414（2022）05-070-06
作者:
刘 伶1; 邹世芳1; 巩 亮1; 齐 晟1; 丁 辉1; 黄 明2
1. 江油市人民医院普外科，四川江油 621799；2 四川省医学科学院·四川省人民医院，成都 610072
Author(s):
LIU Ling1;  ZOU Shi-fang1;  GONG Liang1;  QI Sheng1;  DING Hui1; HUANG Ming2
1. Department of General Surgery, Jiangyou People’s Hospital, Sichuan Jiangyou 621799, China；2. Sichuan Academy of Medical Sciences·Sichuan Provincial People’s Hospital，Chengdu 610072, China
关键词:
乳腺癌; 长链非编码RNAs; 膀胱癌相关转录因子1; E- 钙黏蛋白mRNA
分类号:
R737.9；R730.43
DOI:
10.3969/j.issn.1671-7414.2022.05.015
文献标志码:
A
摘要:
目的　分析血浆外泌体长链非编码RNAs（long non-coding RNAs，LncRNAs）膀胱癌相关转录因子1（bladdercancer associated transcript-1，BLACAT1）和E 钙黏蛋白（E-cadherin）mRNA 在乳腺癌早期诊断中的价值。方法　对江油市人民医院自2019 年1 月～ 2020 年9 月确诊的96 例乳腺癌患者血液样本进行分析，并以75 例在该院进行体检的健康女性血液样本作为对照组。qRT-PCR 检测血浆外泌体中LncRNA BLACAT1 和E-cadherin mRNA 表达水平，分析二者表达水平分别与患者临床病理特征之间的关系，Pearson 法分析乳腺癌患者血浆外泌体中LncRNA BLACAT1 和E-cadherinmRNA 表达的相关性，受试者工作特征（ROC）曲线分析LncRNA BLACAT1 和E-cadherin mRNA 对乳腺癌患者诊断的敏感度和特异度。结果　与健康对照者相比，乳腺癌患者血浆外泌体LncRNA BLACAT1 表达水平显著升高（2.02±0.57vs 0.99±0.03），差异有统计学意义（t=15.622，P=0.000），而E-cadherin mRNA 表达水平显著降低（0.65±0.18 vs1.00±0.04），差异有统计学意义（t=16.514，P=0.000）。血浆外泌体LncRNA BLACAT1 表达水平与乳腺癌患者TNM分期、淋巴结转移、分化程度有关（χ2=5.046 ～ 12.879，均P ＜ 0.05），而与患者年龄、肿瘤大小、雌激素受体（ER）和孕激素受体（PR）无关（χ2=0.107~2.959，均P ＞ 0.05）；E-cadherin mRNA 表达水平与乳腺癌患者TNM 分期、ER和PR、分化程度有关（χ2=6.485 ～ 19.513，均P ＞ 0.05），而与患者年龄、肿瘤大小和淋巴结转移无关（χ2=0.142 ～ 1.289，均P ＞ 0.05）。乳腺癌患者血浆外泌体中LncRNA BLACAT1 与E-cadherin mRNA 水平呈显著性负相关（r =-0.274，P=0.007）。血浆外泌体中LncRNA BLACAT1 和E-cadherin mRNA 单独诊断时的曲线下面积（AUC）分别为0.839 和0.808，敏感度分别为69.80% 和60.00%，特异度分别为89.70% 和88.50%，截断值分别为2.08（95% CI：0.759 ～ 0.919，P ＜ 0.05）和0.48（95% CI：0.719 ～ 0.897，P ＜ 0.05）；联合诊断的AUC 为0.941（95% CI：0.896 ～ 0.985），敏感度和特异度分别为92.30% 和85.60%。结论　血浆外泌体中LncRNA BLACAT1 和E-cadherin mRNA 联合检测可显著提高乳腺癌患者诊断的敏感度，对早期乳腺癌的诊断和后续治疗具有重要意义，二者有望成为未来乳腺癌诊断的有效指标。
Abstract:
Objective　To analyze the value of long non-coding RNAs（LncRNAs） bladder cancer associated transcript-1 (BLACAT1) and E-cadherin in plasma exosomes in the early diagnosis of breast cancer. Methods　The blood samples of 96 breast cancer patients diagnosed in Jiangyou People’s Hospital from January 2019 to September 2020 were analyzed, and blood samples of 75 healthy women who underwent physical examination in the hospital were used as the control group. The expression levels of LncRNA BLACAT1 and E-cadherin mRNA in plasma exosomes were detected with qRT-PCR, the relationship between the expression levels of the two and the clinical pathological characteristics of the patients was analyzed, the correlation between the expression of LncRNA BLACAT1 and E-cadherin mRNA in plasma exosomes of breast cancer patients was analyzed with Pearson method, and the sensitivity and specificity of LncRNA BLACAT1 and E-cadherin mRNA in the diagnosis of breast cancer patients were analyzed with the ROC curve. Results　Compared with healthy controls, the expression level of plasma exosomes LncRNA BLACAT1 in breast cancer patients was significantly increased (2.02±0.57 vs 0.99±0.03), the difference was statistically significant (t=15.622, P=0.000), while the expression level of E-cadherin mRNA was significantly decreased (0.65±0.18 vs 1.00±0.04), and the difference was statistically significant (t=16.514, P=0.000). The expression level of plasma exosomal LncRNA BLACAT1 was related to the TNM stage, lymph node metastasis and differentiation degree of breast cancer patients (χ2=5.046 ～ 12.879, all P ＜ 0.05), and was related to the patient’s age, tumor size, estrogen receptor (ER), progesterone receptor (PR) (χ2=0.107 ～ 2.959, all P ＞ 0.05).The expression level of E-cadherin mRNA was related to the TNM stage, ER, PR and degree of differentiation in breast cancer patients (χ2=6.485 ～ 19.513, all P ＜ 0.05), but was not related to the patient’s age, tumor size, and lymph node metastasis (χ2=0.142 ～ 1.289, all P ＞ 0.05). The levels of LncRNA BLACAT1 and E-cadherin mRNA in plasma exosomes of breast cancer patients were significantly negatively correlated (r=-0.274, P=0.007). The area under the curve (AUC) of LncRNA BLACAT1 and E-cadherin mRNA in plasma exosomes diagnosed separately was 0.839 and 0.808,respectively. The sensitivity was 69.80% and 60.00%, respectively. The specificity was 89.70% and 88.50%, respectively. And the cut-off value was 2.08 (95% CI: 0.759 ～ 0.919, P ＜ 0.05), 0.48 (95% CI: 0.719 ～ 0.897, P ＜ 0.05), respectively. The AUC of the combined diagnosis was 0.941 (95% CI: 0.896 ～ 0.985)，and the sensitivity and the specificity were 92.30% and 85.60%，respectively. Conclusion　The combined detection of LncRNA BLACAT1 and E-cadherin mRNA in plasma exosomes can significantly improve the diagnostic sensitivity of breast cancer patients, and is of great significance for the diagnosis and subsequent treatment of early breast cancer. Both are expected to become effective indicators for future breast cancer diagnosis.

参考文献/References:

[1] GUO Jian, LIU Chen, WANG Wei, et al. Identification of serum miR-1915-3p and miR-455-3p as biomarkers for breast cancer[J]. PLoS One, 2018, 13(7): e0200716.
[2] YOUSEFI H , MAHERONNAGHSH M , MOLAEI F,et al. Long noncoding RNAs and exosomal lncRNAs:classification, and mechanisms in breast cancer metastasis and drug resistance[J]. Oncogene, 2020, 39:953-974.
[3] LIU Lingxia, ZHANG Yu, LU Jun. The roles of long noncoding RNAs in breast cancer metastasis[J]. Cell Death & Disease, 2020, 11(9): 749.
[4] CHENG Hailing, TIAN Jun, WANG Chen, et al.LncRNA BLACAT1 is upregulated in cervical squamous cell carcinoma (CSCC) and predicts poor survival[J]. Reproductive Sciences (Thousand Oaks,Calif.), 2020, 27(2): 585-591.
[5] PADMANABAN V, KROL I, SUHAIL Y, et al.E-cadherin is required for metastasis in multiple models of breast cancer[J]. Nature, 2019, 573(7774): 439-444.
[6] CHEN Feiyu, WANG Ning, TAN Horyue, et al. The functional roles of exosomes-derived long non-coding RNA in human cancer[J]. Cancer Biology & Therapy,2019, 20(5): 583-592.
[7] BARZAMAN K, KARAMI J, ZAREI Z, et al. Breast cancer: Biology, biomarkers, and treatments[J].International Immunopharmacology, 2020, 84(1):106535.
[8] LUO Min, HUANG Yu, HUANG Junqing, et al.Evaluation of the value of GATA3 combined with E-cadherin in the diagnosis of breast cancer[J]. Journal of B U O N, 2019, 24(3): 1038-1044.
[9] LI Yongzhen, SONG Ying, WANG Zhihui, et al. Long non-coding RNA LINC01787 drives breast cancer progression via disrupting mir-125b generation[J].Frontiers in Oncology, 2019, 9(1): 1140.
[10] JABBARI N, AKBARIAZAR E, FEQHHI M, et al.Breast cancer-derived exosomes: Tumor progression and therapeutic agents[J].Journal of Cellular Physiology, 2020, 235(10): 6345-6356.
[11] WU Qi, SUN Si, LI Zhiyu, et al. Breast cancer-released exosomes trigger cancer-associated cachexia to promote tumor progression[J]. Adipocyte, 2019, 8(1): 31-45.
[12] ZHAO Zhuo, SUN Wei, GUO Ziyuan, et al.Mechanisms of lncRNA/microRNA interactions in angiogenesis[J]. Life Sciences, 2020, 254(1): 116900.
[13] ZHU Min, LI Xiao, ZHU Shengtao, et al. Long noncoding RNA BLACAT1, a novel promising biomarker and regulator of human cancers[J]. Biomedicine & Pharmacotherapy, 2020, 132: 110808.
[14] YE Tao, YANG Xiaoqi, LIU Haoran, et al. Long Non-Coding RNA BLACAT1 in human cancers[J].OncoTargets and Therapy, 2020, 13: 8263-8272.
[15] WANG Zhengkun, LIU Xichun, LIU Xiaolei, et al. Long non-coding RNA BLACAT1 promotes the tumorigenesis of gastric cancer by sponging microRNA-149-5p and targeting KIF2A[J]. Cancer Management and Research, 2020, 12(1): 6629-6640.
[16] XU R, CAO X R, ZHANG B Q, et al. BLACAT1 is negatively associated with prognosis in patients with NSCLC and inhibits cell progression, metastasis and epithelial-mesenchymal transition through downregulating Wnt/β-catenin signaling pathway[J].European Review for Medical and Pharmacological Sciences, 2019, 23(14): 6217-6225.
[17] MENDONSA A M, NA T Y, GUMBINER B M.
E-cadherin in contact inhibition and cancer[J].Oncogene, 2018, 37(35): 4769-4780.
[18] 刘郑生, 田海卫, 赵银利.食管鳞状癌组织E-cadherin和Vimentin 的表达与肿瘤浸润和转移的关系[J]. 现代检验医学杂志, 2019, 34(6):50-53.
LIU Zhengsheng, TIAN Haiwei, ZHAO Yinli.
Expression of E-cadherin and vimentin and its relationship with infiltration and metastasis of esophageal aquamous carcinoma [J]. Journal of Modern Laboratory Medicine, 2019, 34(6):50-53.
[19] TAVAKOLIAN S, GOUDARZI H, FAGHIHLOO E.
E-cadherin, Snail, ZEB-1, DNMT1, DNMT3A and DNMT3B expression in normal and breast cancer tissues[J]. Acta Biochimica Polonica, 2019, 66(4): 409-414.
[20] BURE I V, NEMTSOVA M V, ZALETAEV D V. Roles of E-cadherin and noncoding RNAs in the Epithelialmesenchymal transition and progression in gastric cancer[J]. International Journal of Molecular Sciences,2019, 20(12): 2870.

相似文献/References:

[1]党小军,张华,王欣.人附睾蛋白4(HE4)在乳腺癌诊断中的价值[J].现代检验医学杂志,2015,30(06):84.[doi:10.3969/j.issn.1671-7414.2015.06.024]
　DANG Xiao-jun,ZHANG Hua,WANG Xin.Value of Human Epididymis Protein 4(HE4) in Diagnosis of Breast Cancer[J].Journal of Modern Laboratory Medicine,2015,30(05):84.[doi:10.3969/j.issn.1671-7414.2015.06.024]
[2]张 萍,任世云,张 雷.乳腺癌患者血清脂质运载蛋白-2 和基质金属蛋白酶-9的表达及临床意义[J].现代检验医学杂志,2015,30(01):72.[doi:10.3969/j.issn.1671-7414.2015.01.019]
　ZHANG Ping,REN Shi-yun,ZHANG Lei.Expression and Clinical Significance of Serum LCN-2 and MMP-9 in Patients with Breast Cancer[J].Journal of Modern Laboratory Medicine,2015,30(05):72.[doi:10.3969/j.issn.1671-7414.2015.01.019]
[3]乔雪峰a,黄志平b,张 宁c,等.IL-18基因启动子区-137G/C,-607G/T 2个位点基因多态性与女性乳腺癌易感性Meta分析[J].现代检验医学杂志,2016,31(04):65.[doi:10.3969/j.issn.16717-414.2016.04.017]
　QIAO Xue-fenga,HUANG Zhi-pingb,ZHANG Ningc,et al.Association Analysis of IL-18 Gene Promoter Region -137G/C,-607G/T Polymorphisms and Susceptibility to Sporadic Breast Cancer:Meta-Analysis[J].Journal of Modern Laboratory Medicine,2016,31(05):65.[doi:10.3969/j.issn.16717-414.2016.04.017]
[4]刘延梅,马少君,张月浪,等.人类表皮生长因子受体2在乳腺癌表达与临床的相关病理特征分析[J].现代检验医学杂志,2016,31(05):91.[doi:10.3969/j.issn.1671-7414.2016.05.024]
　LIU Yan-mei,MA Shao-jun,ZHANG Yue-lang,et al.Expression of Human Epidermal Growth Factor Receptor 2 and Correlation with Clinical Pathological Features in Breast Cancer[J].Journal of Modern Laboratory Medicine,2016,31(05):91.[doi:10.3969/j.issn.1671-7414.2016.05.024]
[5]陈雨欣,谭婷婷,宁明哲.乳腺癌患者血清中白介素35(IL-35)的表达及其临床意义[J].现代检验医学杂志,2017,32(02):92.[doi:10.3969/j.issn.1671-7414.2017.02.025]
　CHEN Yu-xin,TAN Ting-ting,NING Ming-zhe.Serological Interleukin-35 Level in Patients with Breast Cancer and Its Clinical Significance[J].Journal of Modern Laboratory Medicine,2017,32(05):92.[doi:10.3969/j.issn.1671-7414.2017.02.025]
[6]唐努尔·艾尔肯,阿孜古·祖农.盐酸罗哌卡因对人乳腺癌细胞运动作用的研究[J].现代检验医学杂志,2017,32(03):128.[doi:10.3969/j.issn.1671-7414.2017.03.035]
　TANGNUER·Aierken,AZIGU·Zunong.Study on Effect of Ropivacaine on Migration of Breast Cancer Cell s[J].Journal of Modern Laboratory Medicine,2017,32(05):128.[doi:10.3969/j.issn.1671-7414.2017.03.035]
[7]靳庆娥,苏建荣.北京地区汉族女性人群SYK基因启动子区-803A>Trs290987单核苷酸多态性与乳腺癌易感性分析[J].现代检验医学杂志,2018,33(02):5.[doi:10.3969/j.issn.1671-7414.2018.02.001]
　JIN Qing-e,SU Jian-rong.Associations of SYK Promoter-803A >T(rs290987)Single Nucleotide Polymorphisms with Susceptibility to Breast Cancer of Han Female Population in Beijing Area[J].Journal of Modern Laboratory Medicine,2018,33(05):5.[doi:10.3969/j.issn.1671-7414.2018.02.001]
[8]高 华a,李玉柱b,韩龙才c,等.Logistic回归和ROC工作曲线评价联合检测血清CA153,TPS,CYFRA21-1在乳腺癌诊断中的临床价值[J].现代检验医学杂志,2018,33(03):60.[doi:10.3969/j.issn.1671-7414.2018.03.016]
　GAO Huaa,LI Yu-zhub,HAN Long-caic,et al.Clinical Value of Logistic Regression and ROC Work Curve Evaluating Serum CA153,TPS and Cyfra21-1 for Diagnosis of Breast Cancer[J].Journal of Modern Laboratory Medicine,2018,33(05):60.[doi:10.3969/j.issn.1671-7414.2018.03.016]
[9]李 娜a,赵晓娟b,苏晓明a.乳腺组织中SMG-1mRNA和SOX4mRNA检测在乳腺癌监测中的应用[J].现代检验医学杂志,2019,34(02):35.[doi:10.3969/j.issn.1671-7414.2019.02.010]
　LI Naa,ZHAO Xiao-juanb,SU Xiao-minga.Application of Detection of SMG-1mRNA and SOX4mRNAin Breast Tissue in Surveillance for Breast Cancer[J].Journal of Modern Laboratory Medicine,2019,34(05):35.[doi:10.3969/j.issn.1671-7414.2019.02.010]
[10]王 碧,吉茂礼.乳腺癌组织长链非编码RNA UCA1和BCAR4表达与辅助化疗效果的相关性研究[J].现代检验医学杂志,2019,34(05):77.[doi:10.3969/j.issn.1671-7414.2019.05.019]
　WANG Bi,JI Mao-li.Correlational Research on the Expressionof Long-Chain Non-Coding RNA UCA1 and BCAR4in Breast Cancer Tissues for the Effect of Adjuvant Chemotherapy[J].Journal of Modern Laboratory Medicine,2019,34(05):77.[doi:10.3969/j.issn.1671-7414.2019.05.019]

备注/Memo

备注/Memo:
基金项目：四川省卫生健康委员会项目（19PJ136）。
作者简介：刘伶（1974-），女，大学本科，主治医师，研究方向：基本外科相关的临床与基础研究，E-mail：ll1967@yeah.net。
通讯作者：丁辉（1962-），男，大学本科，主任医师，研究方向：基本外科相关的临床与基础研究， E-mail：dinghui1962@126.com。
更新日期/Last Update: 2022-09-15