血浆长链非编码RNA HOTTIP、ATB和MIAT在乳腺癌中的临床价值研究
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摘要
目的探究血浆长链非编码RNA(LncRNA)HOTTIP、ATB和MIAT对乳腺癌的诊断价值及三者与乳腺癌临床病理特征之间的关系。方法收取重庆市璧山区人民医院2014年3月至2017年12月确诊的乳腺癌患者245例为病例组,与同期在该院行体检健康者250例作为对照组。比较两组研究对象血浆LncRNA HOTTIP、ATB和MIAT表达水平的差异,并分析三者表达水平与乳腺癌患者临床病理特征之间的关系。运用受试者工作特征曲线(ROC)分析血浆LncRNA HOTTIP、ATB和MIAT对乳腺癌的诊断价值,多元logistic回归计算风险比(OR)及95%置信区间(CI)。结果病例组血浆LncRNA HOTTIP、ATB和MIAT表达水平均高于对照组,差异具有统计学意义(P<0.05)。三者均与乳腺癌的分子分型、TNM分期显著相关(P<0.05)。ROC分析显示,血浆LncRNA HOTTIP、ATB和MIAT鉴别诊断乳腺癌的曲线下面积(AUC)分别为:0.784(95%CI:0.701～0.866,P<0.001)、0.887(95%CI:0.822～0.951,P<0.001)和0.913(95%CI:0.855～0.971,P<0.001);灵敏度/特异度分别为63.8%/89.3%、79.7%/91.7%和87.1%/92.8%,联合三项指标的灵敏度为85.5%,特异度为97.6%,优于单项指标检测。多元Logistic回归分析表明,血浆高LncRNA HOTTIP、ATB和MIAT表达水平均是乳腺癌发病的独立危险因素。结论联合血浆LncRNA HOTTIP、ATB和MIAT三项指标可协助乳腺癌的诊断,同时,三者对乳腺癌病情程度与发病风险的评估也具有潜在价值。
Objective To explore the diagnostic values of long non-coding RNA(lncRNA)HOTTIP,ATB and MIAT for breast cancer,and the relationship between the three and the clinicopathological features of breast cancer.Methods 245 cases of breast cancer diagnosed in the people′s hospital of Bishan district from March 2014 to December 2017 were collected,and 250 healthy people were recruited in a hospital during the same period.The differences in the levels of plasma LncRNA HOTTIP,ATB and MIAT were compared between the two groups,and the relationship between the expression level of the three and the clinicopathological features of the patients with breast cancer was analyzed.Receiver operating characteristic curve(ROC)was used to analyze the diagnostic value of plasma lncRNA HOTTIP,ATB and MIAT for breast cancer.Multiple logistic regression was used to calculate the odds ratio(OR)and the 95%confidence interval(CI).ResultsPlasma lncRNA Linc00152,H19 and ROR levels in patients with esophageal cancer were significantly higher than those in healthy subjects,and the difference were statistically significant(P<0.05).The levels of plasma lncRNA HOTTIP,ATB and MIAT in case group were higher than those in control group,and the difference was statistically significant(P<0.05).The three were significantly correlated with the molecular typing and TNM staging of breast cancer(P<0.05).The area under the curve(AUC)of LncRNA HOTTIP,ATB and MIAT in the differential diagnosis of breast cancer were 0.784(95%CI:0.701-0.866,P<0.001),0.887(95%CI:0.822-0.951,P<0.001)and 0.913(95%CI:0.855-0.971,P<0.001),and the sensitivity/specificity of lncRNA HOTTIP,ATB and MIAT in the differential diagnosis of breast cancer were 63.8%/89.3%,79.7%/91.7% and 87.1%/92.8%,respectively.The sensitivity of the combined three indexes was 85.5%and the specificity was 97.6%,which was better than the single index detection.Multivariate logistic regression analysis showed that plasma high lncRNA HOTTIP,ATB and MIAT expression levels were independent risk factors for breast cancer.Conclusion The combination of HOTTIP,ATB,and MIAT can assist in the diagnosis of breast cancer.At the same time,the three are also of potential value for the assessment of the degree of breast cancer and the risk of the disease.
Objective To explore the diagnostic values of long non-coding RNA(lncRNA)HOTTIP,ATB and MIAT for breast cancer,and the relationship between the three and the clinicopathological features of breast cancer.Methods 245 cases of breast cancer diagnosed in the people′s hospital of Bishan district from March 2014 to December 2017 were collected,and 250 healthy people were recruited in a hospital during the same period.The differences in the levels of plasma LncRNA HOTTIP,ATB and MIAT were compared between the two groups,and the relationship between the expression level of the three and the clinicopathological features of the patients with breast cancer was analyzed.Receiver operating characteristic curve(ROC)was used to analyze the diagnostic value of plasma lncRNA HOTTIP,ATB and MIAT for breast cancer.Multiple logistic regression was used to calculate the odds ratio(OR)and the 95%confidence interval(CI).ResultsPlasma lncRNA Linc00152,H19 and ROR levels in patients with esophageal cancer were significantly higher than those in healthy subjects,and the difference were statistically significant(P<0.05).The levels of plasma lncRNA HOTTIP,ATB and MIAT in case group were higher than those in control group,and the difference was statistically significant(P<0.05).The three were significantly correlated with the molecular typing and TNM staging of breast cancer(P<0.05).The area under the curve(AUC)of LncRNA HOTTIP,ATB and MIAT in the differential diagnosis of breast cancer were 0.784(95%CI:0.701-0.866,P<0.001),0.887(95%CI:0.822-0.951,P<0.001)and 0.913(95%CI:0.855-0.971,P<0.001),and the sensitivity/specificity of lncRNA HOTTIP,ATB and MIAT in the differential diagnosis of breast cancer were 63.8%/89.3%,79.7%/91.7% and 87.1%/92.8%,respectively.The sensitivity of the combined three indexes was 85.5%and the specificity was 97.6%,which was better than the single index detection.Multivariate logistic regression analysis showed that plasma high lncRNA HOTTIP,ATB and MIAT expression levels were independent risk factors for breast cancer.Conclusion The combination of HOTTIP,ATB,and MIAT can assist in the diagnosis of breast cancer.At the same time,the three are also of potential value for the assessment of the degree of breast cancer and the risk of the disease.
引文
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[12]李观强,杨辉,洪雄新,等.2型糖尿病患者ABCA1、PPARγ、SREBP、ADPN、LXRα表达水平及临床价值研究[J].国际检验医学杂志,2018,39(10):1199-1201.
[13]SHI S J,WANG L J,YU B,et al.LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer[J].Oncotarget,2015,6(13):11652-11663.
[14]NIKPAYAM E,SOUDYAB M,TASHARROFI B,et al.Expression analysis of long non-coding ATB and its putative target in breast cancer[J].Breast Dis,2017,37(1):11-20.
[15]LUAN T,ZHANG X,WANG S,et al.Long non-coding RNA MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7expression by sponging miR-155-5p[J].Oncotarget,2017,8(44):76153-76164.
[16]ALIPOOR F J,ASADI M H,TORKZADEH-MAHANI M.MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers senescence and G1arrest in MCF7cell line[J].J Cell Biochem,2018,119(8):6470-6481.
[2]郑莹,吴春晓,张敏璐.乳腺癌在中国的流行状况和疾病特征[J].中国癌症杂志,2013,23(8):561-569.
[3]黄哲宙,陈万青,吴春晓,等.中国女性乳腺癌的发病和死亡现况--全国32个肿瘤登记点2003-2007年资料分析报告[J].肿瘤,2012,32(6):435-439.
[4]陈双双,于正洪.长链非编码RNAs在乳腺癌中的表达及其功能[J].临床肿瘤学杂志,2015,20(10):943-947.
[5]周斌,季科,辛灵,等.美国肿瘤联合会乳腺癌分期系统(第8版)更新内容介绍及解读[J].中国实用外科杂志,2017,37(1):10-14.
[6]师金,梁迪,李道娟,等.全球女性乳腺癌流行情况研究[J].中国肿瘤,2017,26(9):683-690.
[7]左婷婷,陈万青.中国乳腺癌全人群生存率分析研究进展[J].中国肿瘤临床,2016,43(14):639-642.
[8]中国乳腺癌内分泌治疗专家共识专家组.中国乳腺癌内分泌治疗专家共识(2015年版)[J].中国癌症杂志,2015,25(9):755-760.
[9]庞英,FISCHER Irmela,KOCH Maike,等.乳腺癌患者的心身症状与生活质量[J].中国心理卫生杂志,2013,27(4):257-261.
[10]江泽飞,许凤锐.乳腺癌分子分型对治疗的影响[J/CD].中华普外科手术学杂志(电子版),2015,9(6):12-15.
[11]YANG Y,QIAN J,XIANG Y,et al.The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer[J].Oncotarget,2017,8(4):6833-6844.
[12]李观强,杨辉,洪雄新,等.2型糖尿病患者ABCA1、PPARγ、SREBP、ADPN、LXRα表达水平及临床价值研究[J].国际检验医学杂志,2018,39(10):1199-1201.
[13]SHI S J,WANG L J,YU B,et al.LncRNA-ATB promotes trastuzumab resistance and invasion-metastasis cascade in breast cancer[J].Oncotarget,2015,6(13):11652-11663.
[14]NIKPAYAM E,SOUDYAB M,TASHARROFI B,et al.Expression analysis of long non-coding ATB and its putative target in breast cancer[J].Breast Dis,2017,37(1):11-20.
[15]LUAN T,ZHANG X,WANG S,et al.Long non-coding RNA MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7expression by sponging miR-155-5p[J].Oncotarget,2017,8(44):76153-76164.
[16]ALIPOOR F J,ASADI M H,TORKZADEH-MAHANI M.MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers senescence and G1arrest in MCF7cell line[J].J Cell Biochem,2018,119(8):6470-6481.