乳腺癌相关基因CK19与Vimentin mRNA联合检测在乳腺癌中的临床应用

doi:10.3877/cma.j.issn.1674-3946.2021.04.019

目的

探讨逆转录聚合酶链反应(RT-qPCR)法检测乳腺癌患者外周血中CK19、Vimentin mRNA表达量及临床意义。

方法

RT-qPCR法测定73例乳腺癌患者和24例健康女性体检者外周血中CK19与Vimentin mRNA的表达量。使用SPSS20.0软件进行统计分析，CK19与Vimentin mRNA表达量等计量资料等用(±s)表示，组间比较采用独立t检验。受试者工作特征曲线(ROC曲线)通过建立二元Logistc回归模型绘制，分析外周血中CK19与Vimentin及二者联合对乳腺癌诊断的潜在价值。以P<0.05为差异有统计学意义。

结果

CK19与Vimentin的mRNA在乳腺癌组的表达量大于健康对照组(P<0.05)。CK19诊断乳腺癌的ROC曲线下面积(AUC)为0.689，灵敏度63%，特异度75%。Vimentin AUC为0.709，灵敏度41.1%，特异度91.7%。二者联合诊断乳腺癌的AUC为0.740。CK19 mRNA表达量与乳腺癌患者是否绝经相关(P<0.05)。

结论

CK19与Vimentin mRNA在乳腺癌患者中表达均上调，对乳腺癌有良好的诊断效能，可能是乳腺癌辅助诊断的潜在生物标志物。

关键词: 乳腺肿瘤, 波形蛋白, 逆转录聚合酶链反应, 细胞角蛋白19

Objective

To explore the use of reverse transcription polymerase chain reaction (RT-qPCR) detecting the expression of CK19 and Vimentin mRNA in the peripheral blood of patients with breast cancer and its clinical significance.

Methods

Using RT-qPCR detect CK19 and Vimentin mRNA expression in peripheral blood of 73 patients with breast cancer and 24 healthy controls. Spss20.0 software was used for statistical analysis. CK19 and Vimentin mRNA expression and other measurement data were expressed as (±s). Independent t test was used for comparison between groups. Receiver operating characteristic curve (ROC) was drawn by establishing binary logistic regression model. Analyze the potential value of CK19, Vimentin and their combination in the peripheral blood for the diagnosis of breast cancer. A P value of <0.05 was considered as statistically significant difference.

Results

The expression of CK19 and vimentin mRNA in breast cancer group were significantly higher than those in healthy control group (P<0.05). The area under ROC curve (AUC) of CK19 was 0.689, the sensitivity was 63.0%, and the specificity was 75%. The AUC of vimentin was 0.709, the sensitivity was 41.1%, and the specificity was 91.7%. While the AUC of CK19 combined with Vimentin in the diagnosis of breast cancer was 0.740. The expression of CK19 mRNA was associated with menopausal status of breast cancer patients (P<0.05).

Conclusion

Both CK19 and Vimentin mRNA are up-regulated in patients with breast cancer, which have satisfactory diagnostic efficiency for breast cancer and probably become the potential biomarkers to assist the diagnosis of breast cancer.

Key words: Breast neoplasms, Vimentin, Reverse transcriptase polymerase chain reaction, Cytokeratin 19

图1 CK19、Vimentin与GAPDH1扩增曲线图

表1 CK19与Vimentin mRNA在乳腺癌组和健康对照组的表达情况

组别	例数	CK19	Vimentin
健康对照组	24	0.69±0.50	0.92±0.34
乳腺癌组	73	1.55±1.57^a	1.16±0.37^a

表1 CK19与Vimentin mRNA在乳腺癌组和健康对照组的表达情况

组别	例数	CK19	Vimentin
健康对照组	24	0.69±0.50	0.92±0.34
乳腺癌组	73	1.55±1.57^a	1.16±0.37^a

图2 乳腺癌组与健康对照组CK19与Vimentin的ROC曲线图

表2 73例乳腺癌患者CK19与Vimentin mRNA诊断效率的比较(%)

项目	灵敏度	特异度	阳性似然比	阴性似然比	AUC	95%CI
CK19	63.0	75.0	88.46	40.0	0.689	0.587～0.779
Vimentin	41.1	91.67	93.75	33.85	0.709	0.608～0.796
CK19+Vimentin	64.38	79.2	90.38	42.22	0.740	0.641～0.824

表2 73例乳腺癌患者CK19与Vimentin mRNA诊断效率的比较(%)

项目	灵敏度	特异度	阳性似然比	阴性似然比	AUC	95%CI
CK19	63.0	75.0	88.46	40.0	0.689	0.587～0.779
Vimentin	41.1	91.67	93.75	33.85	0.709	0.608～0.796
CK19+Vimentin	64.38	79.2	90.38	42.22	0.740	0.641～0.824

表3 CK19和Vimentin表达量与73例乳腺癌患者临床特征的相关性

病理特征		例数	CK19	P值	Vimentin	P值
年龄(岁)
	<50	42	1.31±1.22	0.271	1.22±0.44	0.112
	≥50	31	1.67±1.51	0.271	1.08±0.25	0.112
绝经状态
	绝经前	51	1.22±1.13	0.047	1.19±0.41	0.357
	绝经后	22	2.02±1.65	0.047	1.10±0.27	0.357
淋巴结转移
	是	32	1.21±1.23	0.296	1.15±0.36	0.933
	否	41	1.55±1.38	0.296	1.16±0.42	0.933
Ki67
	≥15%	59	1.47±1.36	0.933	1.17±0.40	0.471
	<15%	14	1.44±1.35	0.933	1.09±0.27	0.471
临床分期
	Ⅰ+Ⅱ期	62	1.50±1.40	0.38	1.18±0.39	0.216
	Ⅲ+Ⅳ期	11	1.26±1.07	0.38	1.04±0.23	0.216
ER状态
	阳性	44	1.33±1.27	0.292	1.09±0.31	0.060
	阴性	29	1.67±1.46	0.292	1.26±0.44	0.060
PR状态
	阳性	36	1.41±1.37	0.758	1.24±0.40	0.071
	阴性	37	1.51±1.35	0.758	1.08±0.33	0.071
CerbB-2
	阳性	32	1.40±1.41	0.742	1.11±0.37	0.384
	阴性	41	1.51±1.32	0.742	1.19±0.38	0.384

表3 CK19和Vimentin表达量与73例乳腺癌患者临床特征的相关性

病理特征		例数	CK19	P值	Vimentin	P值
年龄(岁)
	<50	42	1.31±1.22	0.271	1.22±0.44	0.112
	≥50	31	1.67±1.51	0.271	1.08±0.25	0.112
绝经状态
	绝经前	51	1.22±1.13	0.047	1.19±0.41	0.357
	绝经后	22	2.02±1.65	0.047	1.10±0.27	0.357
淋巴结转移
	是	32	1.21±1.23	0.296	1.15±0.36	0.933
	否	41	1.55±1.38	0.296	1.16±0.42	0.933
Ki67
	≥15%	59	1.47±1.36	0.933	1.17±0.40	0.471
	<15%	14	1.44±1.35	0.933	1.09±0.27	0.471
临床分期
	Ⅰ+Ⅱ期	62	1.50±1.40	0.38	1.18±0.39	0.216
	Ⅲ+Ⅳ期	11	1.26±1.07	0.38	1.04±0.23	0.216
ER状态
	阳性	44	1.33±1.27	0.292	1.09±0.31	0.060
	阴性	29	1.67±1.46	0.292	1.26±0.44	0.060
PR状态
	阳性	36	1.41±1.37	0.758	1.24±0.40	0.071
	阴性	37	1.51±1.35	0.758	1.08±0.33	0.071
CerbB-2
	阳性	32	1.40±1.41	0.742	1.11±0.37	0.384
	阴性	41	1.51±1.32	0.742	1.19±0.38	0.384

[1]	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[2]	乌拉木·玉努斯，周娜，柳紫阳，等. 超声筛查乳腺癌模式在基层医院应用的研究[J]. 中国癌症杂志，2019，29(2)：148-152.
[3]	Lee J, Park S, Lee Y, et al. Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumor DNA[J]. Mol Oncol, 2019, 13(8): 1623-1650.
[4]	Winter A, Engels S, Goos P, et al. Detection of CK19 mR-NA using one-step nucleic acid amplification (OSNA) in prostate cancer: preliminary results[J]. J Cancer, 2018, 9(24): 4611-4617.
[5]	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[6]	Jafari SH, Saadatpour Z, Salmaninejad A, et al. Breast cancer diagnosis: Imaging techniques and biochemical markers[J]. J Cell Physiol, 2018, 233(7): 5200-5213.
[7]	Huang L, Wang X, Huang X, et al. Diagnostic significance of CK19, galectin-3, CD56, TPO and Ki67 expression and BRAF mutation in papillary thyroid carcinoma[J]. Oncol Lett, 2018, 15(4): 4269-4277.
[8]	Zhao L, Zhang P, Su X-J, et al. The ubiquitin ligase TRIM56 inhibits ovarian cancer progression by targeting vimentin[J]. J Cell Physiol, 2018, 233(3): 2420-2425.
[9]	Aruga N, Kijima H, Masuda R, et al. Epithelial-mesenchymal transition(EMT)is correlated with patient’s prognosis of lung squamous cell carcinoma[J]. Tokai J Exp Clin Med, 2018, 43(1): 5-13.
[10]	殷红梅. 基于数据库分析CK-19基因在乳腺癌中的表达及与患者预后相关性[J]. 转化医学杂志，2020，9(4)：202-205
[11]	王合兵，肖坚，陈文新，等. 外周血细胞角蛋白-19和Vimentin mRNA在乳腺癌早期诊断中的应用价值[J]. 中国肿瘤临床与康复，2019，26(5)：517-520.
[12]	Kwan TT, Bardia A, Spring LM, et a1. A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic Response in Localized and Metastatic Breast Cancer[J]. Cancer Discov, 2018, 8(10): 1286-1299.

[1]	李洋, 蔡金玉, 党晓智, 常婉英, 巨艳, 高毅, 宋宏萍. 基于深度学习的乳腺超声应变弹性图像生成模型的应用研究[J/OL]. 中华医学超声杂志（电子版）, 2024, 21(06): 563-570.
[2]	河北省抗癌协会乳腺癌专业委员会护理协作组. 乳腺癌中心静脉通路护理管理专家共识[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 321-329.
[3]	刘晨鹭, 刘洁, 张帆, 严彩英, 陈倩, 陈双庆. 增强MRI 影像组学特征生境分析在预测乳腺癌HER-2 表达状态中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 339-345.
[4]	张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[5]	邱琳, 刘锦辉, 组木热提·吐尔洪, 马悦心, 冷晓玲. 超声影像组学对致密型乳腺背景中非肿块型乳腺癌的诊断价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 353-360.
[6]	程燕妮, 樊菁, 肖瑶, 舒瑞, 明昊, 党晓智, 宋宏萍. 乳腺组织定位标记夹的应用与进展[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 361-365.
[7]	涂盛楠, 胡芬, 张娟, 蔡海峰, 杨俊泉. 天然植物提取物在乳腺癌治疗中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 366-370.
[8]	朱文婷, 顾鹏, 孙星. 非酒精性脂肪性肝病对乳腺癌发生发展及治疗的影响[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 371-375.
[9]	周荷妹, 金杰, 叶建东, 夏之一, 王进进, 丁宁. 罕见成人肋骨郎格汉斯细胞组织细胞增生症被误诊为乳腺癌术后骨转移一例[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 380-383.
[10]	葛睿, 陈飞, 李杰, 李娟娟, 陈涵. 多基因检测在早期乳腺癌辅助治疗中的应用价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(05): 257-263.
[11]	高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[12]	韩萌萌, 冯雪园, 马宁. 乳腺癌改良根治术后桡神经损伤1例[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 117-118.
[13]	张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[14]	王玲艳, 高春晖, 冯雪园, 崔鑫淼, 刘欢, 赵文明, 张金库. 循环肿瘤细胞在乳腺癌新辅助及术后辅助治疗中的应用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 630-633.
[15]	赵林娟, 吕婕, 王文胜, 马德茂, 侯涛. 超声引导下染色剂标记切缘的梭柱型和圆柱型保乳区段切除术的效果研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 634-637.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Clinical application of combined detection of breast cancer related gene CK19 with Vimentin mRNA in breast cancer

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Clinical application of combined detection of breast cancer related gene CK19 with Vimentin mRNA in breast cancer