乳腺癌组织中长链非编码RNA TUG1的表达及临床意义
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摘要
目的探讨长链非编码RNA牛磺酸上调基因1(TUG1)在乳腺癌组织中的表达及临床意义。方法收集本院2013年1月至2015年12月女性乳腺癌患者手术切除的113对癌组织和癌旁组织,采用实时定量PCR(QPCR)检测以上组织中TUG1的表达并比较TUG1在癌组织和癌旁组织中的分布差异,采用受试者工作特征曲线(ROC)分析组织TUG1水平诊断乳腺癌的效能,进一步分析TUG1表达与乳腺癌临床病理特征(年龄、肿瘤大小、淋巴结转移、TNM分期、绝经、组织学分级、ER、PR、HER-2和Ki-67表达及Nottingham预后指数)的关系,采用Kaplan-Meier Plotter肿瘤预后评价数据库分析TUG1表达与乳腺癌预后的关系。结果 QPCR检测结果显示,乳腺癌组织的TUG1水平为2.529±0.967,高于癌旁组织的1.096±0.480(P<0.05);ROC曲线分析显示组织TUG1水平诊断乳腺癌的曲线下面积为0.905(95%CI:0.866～0.944),当取约登指数最大的2.002为截断值时,敏感度和特异度分别为70.80%和98.23%。乳腺癌患者TUG1水平与年龄、绝经、组织学分级、ER表达及PR表达均无关,而与淋巴结转移、肿瘤大小、TNM分期、HER-2表达、Ki-67表达及Nottingham预后指数有关(P<0.05)。Kaplan-Meier Plotter数据库在线分析显示TUG1表达与无复发生存期、总生存期和进展后生存期均无关,而与无远处转移生存期有关,其中TUG1低表达者的优于高表达(HR=1.88,95%CI:1.30～2.72,P<0.001)。结论 TUG1在乳腺癌中高表达且与肿瘤的发生发展和预后有一定关系,在乳腺癌筛查及预后预测上有一定的潜在价值。
Objective To investigate the expression of long non-coding RNA taurine upregulated gene 1(TUG1) in breast cancer tissues and its clinical significance. Methods From January 2013 to December 2015, 113 pairs of cancerous and paracancerous tissues surgically removed from patients with breast cancer were collected. Real-time quantitative PCR(QPCR) was used to detect the expression of TUG1 in the above tissues and the distribution of TUG1 in cancer tissues and adjacent tissues were compared. The receiver operating characteristic(ROC) curve was used to analyze the diagnostic efficacy of TUG1 level in breast cancer tissues. The relationship between TUG1 expression and clinicopathological features of breast cancer(age, tumor size, lymph node metastasis, TNM stage, menopause, histological grade, ER, PR, HER-2 and Ki-67 expression and Nottingham prognostic index) was further analyzed. The relationship between TUG1 expression and prognosis of breast cancer was analyzed by Kaplan-Meier Plotter tumor prognosis evaluation database. Results The results of QPCR showed that the TUG1 level in breast cancer tissues was 2.529±0.967, higher than 1.096±0.480 in adjacent tissues(P<0.05). ROC curve analysis showed that the area under the curve of tissue TUG1 level in diagnosis of breast cancer was 0.905(95%CI: 0.866-0.944). When the truncated value is 2.002 of the largest Jordan index, the sensitivity and specificity were 70.80% and 98.23%. TUG1 level in breast cancer tissues was not related to age, menopause, histological grade, ER expression and PR expression, but related to lymph node metastasis, tumor size, TNM stage, HER-2 expression, Ki-67 expression and Nottingham prognostic index(P<0.05). The online analysis of Kaplan-Meier Plotter database showed that the expression of TUG1 was not related to recurrence-free survival, overall survival and progression-free survival, but related to distant metastasis-free survival. The lower expression of TUG1 was better than the higher expression(HR=1.88, 95% CI: 1.30-2.72, P<0.001)in term of distant metastasis-free survival. Conclusion TUG1 was highly expressed in breast cancer and related to tumor progress and prognosis in breast cancer. These findings indicate that TUG1 might serve as a potential biomarker for the detection of breast cancer.
Objective To investigate the expression of long non-coding RNA taurine upregulated gene 1(TUG1) in breast cancer tissues and its clinical significance. Methods From January 2013 to December 2015, 113 pairs of cancerous and paracancerous tissues surgically removed from patients with breast cancer were collected. Real-time quantitative PCR(QPCR) was used to detect the expression of TUG1 in the above tissues and the distribution of TUG1 in cancer tissues and adjacent tissues were compared. The receiver operating characteristic(ROC) curve was used to analyze the diagnostic efficacy of TUG1 level in breast cancer tissues. The relationship between TUG1 expression and clinicopathological features of breast cancer(age, tumor size, lymph node metastasis, TNM stage, menopause, histological grade, ER, PR, HER-2 and Ki-67 expression and Nottingham prognostic index) was further analyzed. The relationship between TUG1 expression and prognosis of breast cancer was analyzed by Kaplan-Meier Plotter tumor prognosis evaluation database. Results The results of QPCR showed that the TUG1 level in breast cancer tissues was 2.529±0.967, higher than 1.096±0.480 in adjacent tissues(P<0.05). ROC curve analysis showed that the area under the curve of tissue TUG1 level in diagnosis of breast cancer was 0.905(95%CI: 0.866-0.944). When the truncated value is 2.002 of the largest Jordan index, the sensitivity and specificity were 70.80% and 98.23%. TUG1 level in breast cancer tissues was not related to age, menopause, histological grade, ER expression and PR expression, but related to lymph node metastasis, tumor size, TNM stage, HER-2 expression, Ki-67 expression and Nottingham prognostic index(P<0.05). The online analysis of Kaplan-Meier Plotter database showed that the expression of TUG1 was not related to recurrence-free survival, overall survival and progression-free survival, but related to distant metastasis-free survival. The lower expression of TUG1 was better than the higher expression(HR=1.88, 95% CI: 1.30-2.72, P<0.001)in term of distant metastasis-free survival. Conclusion TUG1 was highly expressed in breast cancer and related to tumor progress and prognosis in breast cancer. These findings indicate that TUG1 might serve as a potential biomarker for the detection of breast cancer.
引文
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[2] Lai SF,Chen YH,Liang TH,et al.The breast graded prognostic assessment is associated with the survival outcomes in breast cancer patients receiving whole brain re-irradiation [J].J Neurooncol,2018,138(3):637-647.
[3] Sang J,Yi D,Tang X,et al.The associations between mast cell infiltration,clinical features and molecular types of invasive breast cancer [J].Oncotarget,2016,7(49):81661-81669.
[4] Zhou M,Zhang Z,Zhao H,et al.An immune-related six-lncRNA signature to improve prognosis prediction of glioblastoma multiforme [J].Mol Neurobiol,2018,55(5):3684-3697.
[5] Xue X,Yang YA,Zhang A,et al.LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer [J].Oncogene,2016,35(21):2746-2755.
[6] Xiao C,Wu CH,Hu HZ.LncRNA UCA1 promotes epithelial-mesenchymal transition(EMT) of breast cancer cells via enhancing Wnt/beta-catenin signaling pathway [J].Eur Rev Med Pharmacol Sci,2016,20(13):2819-2824.
[7] Xu Y,Leng K,Li Z,et al.The prognostic potential and carcinogenesis of long non-coding RNA TUG1 in human cholangiocarcinoma [J].Oncotarget,2017,8(39):65823-65835.
[8] Hu Y,Sun X,Mao C,et al.Upregulation of long noncoding RNA TUG1 promotes cervical cancer cell proliferation and migration [J].Cancer Med,2017,6(2):471-482.
[9] Wang Y,Yang T,Zhang Z,et al.Long non-coding RNA TUG1 promotes migration and invasion by acting as a ceRNA of miR-335-5p in osteosarcoma cells [J].Cancer Sci,2017,108(5):859-867.
[10] Cai H,Xue Y,Wang P,et al.The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144 [J].Oncotarget,2015,6(23):19759-19779.
[11] Hsiao FH,Kuo WH,Jow GM,et al.The changes of quality of life and their correlations with psychosocial factors following surgery among women with breast cancer from the post-surgery to post-treatment survivorship [J].Breast,2019,44:59-65.
[12] Zhang K,Luo Z,Zhang Y,et al.Circulating lncRNA H19 in plasma as a novel biomarker for breast cancer [J].Cancer Biomark,2016,17(2):187-194.
[13] Han Y,Liu Y,Gui Y,et al.Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder [J].J Surg Oncol,2013,107(5):555-559.
[14] Zhang Q,Geng PL,Yin P,et al.Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis [J].Asian Pac J Cancer Prev,2013,14(4):2311-2315.
[15] Xu Y,Wang J,Qiu M,et al.Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma [J].Tumour Biol,2015,36(3):1643-1651.
[16] Zhang E,He X,Yin D,et al.Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57 [J/OL].Cell Death Dis,2016[2018-09-22].https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26913601.
[17] Li Z,Shen J,Chan MT,et al.TUG1:a pivotal oncogenic long non-coding RNA of human cancers [J].Cell Prolif,2016,49(4):471-475.
[18] Wang PQ,Wu YX,Zhong XD,et al.Prognostic significance of overexpressed long non-coding RNA TUG1 in patients with clear cell renal cell carcinoma [J].Eur Rev Med Pharmacol Sci,2017,21(1):82-86.
[19] Liang S,Zhang S,Wang P,et al.LncRNA,TUG1 regulates the oral squamous cell carcinoma progression possibly via interacting with Wnt/β-catenin signaling [J].Gene,2017,608:49-57.
[20] Niu Y,Feng M,Huang W,et al.Long non-coding RNA TUG1 is involved in cell growth and chemoresistance of small cell lung cancer by regulating LIMK2b via EZH2 [J].Mol Cancer,2017,16(1):5.
[21] Zhang CG,Yin DD,Sun SY,et al.The use of lncRNA analysis for stratification management of prognostic risk in patients with NSCLC [J].Eur Rev Med Pharmacol Sci,2017,21(1):115-119.
[22] Quintyne KI,Woulfe B,Coffey JC,et al.Correlation between Nottingham prognostic index and adjuvant online prognostic tools in patients with early-stage breast cancer in Mid-Western Ireland [J].Clin Breast Cancer,2013,13(4):233-238.