BI-RADS分级联合PD-1可有效诊断乳腺癌
|
摘要
为探讨BI-RADS分级联合PD-1在乳腺癌患者中的诊断效果,本研究选取在2016年1月至2017年1月就诊于我院超声科的153例乳腺肿瘤患者作为研究对象。本研究于治疗前采集患者外周血,使用荧光定量PCR技术进行PD-1 m RNA检测,并以20例年龄、性别相匹配的健康人作为对照。采用x2检验或Fisher精确检验分析乳腺癌患者临床病理信息与BI-RADS和PD-1 m RNA的关系,使用ROC曲线评价乳腺超声BI-RADS分级、PD-1 m RNA表达及两者联合的诊断价值。数据显示,乳腺超声BI-RADS分级诊断的灵敏度为89%、特异度为74%、曲线下面积为0.888(p<0.001);PD-1 m RNA表达诊断灵敏度为78%、特异度为77%、曲线下面积为0.826(p<0.001);两者联合诊断的灵敏度为91%、特异度为87%、曲线下面积为0.918(p<0.001)。乳腺癌患者中,肿瘤越大、分期越晚的患者BI-RADS分级越高;孕激素受体阳性患者PD-1 m RNA表达升高。本研究表明,乳腺超声BI-RADS分级联合PD-1检测的诊断价值优于两者单独的诊断价值,能成为诊断乳腺癌的一种有效方法,值得在临床上推广使用。
In order to investigate the diag nostic value of breast ultrasound breast imaging reporting and data system(BI-RADS) classification combined with programmed death 1(PD-1) detection in breast cancer patients.This study enrolled 153 patients with breast tumor who were admitted to our hospital from Jan 2016 to Jan 2017.Peripheral blood was collected before treatment and tested for m RNA expression of PD-1 by quantitative Real-time PCR. Twenty age and sex-matched healthy people were selected as controls. χ~2 test and fisher exact test were used to evaluate the relationship between clinicopathological information and BI-RADS and PD-1 in breast cancer patients. And the ROC curve was used to evaluate the diagnostic value of BI-RADS classification, PD-1mRNA expression and the combination of these two. The results revealed that the sensitivity of breast ultrasound BI-RADS classification was 89%, the specificity was 74%, the area under the curve was 0.888(p <0.001); the diagnostic sensitivity of PD-1 mRNA expression was 78%, the specificity was 77%, the area under the curve was 0.826(p<0.001); the combined sensitivity of these two was 91%, the specificity was 87%, and the area under the curve was 0.918(p<0.001). In breast cancer patients, high tumor diameter and stage predicted increased BI-RADS grade; progesterone receptor positive patients showed an increase of PD-1 mRNA expression. This study suggesedthat the diagnostic value of breast ultrasound BI-RADS classification combined with PD-1 detection could superior to the diagnostic value of both, which may be an effective method for the diagnosis of breast cancer and it might worth to use in clinical practice.
In order to investigate the diag nostic value of breast ultrasound breast imaging reporting and data system(BI-RADS) classification combined with programmed death 1(PD-1) detection in breast cancer patients.This study enrolled 153 patients with breast tumor who were admitted to our hospital from Jan 2016 to Jan 2017.Peripheral blood was collected before treatment and tested for m RNA expression of PD-1 by quantitative Real-time PCR. Twenty age and sex-matched healthy people were selected as controls. χ~2 test and fisher exact test were used to evaluate the relationship between clinicopathological information and BI-RADS and PD-1 in breast cancer patients. And the ROC curve was used to evaluate the diagnostic value of BI-RADS classification, PD-1mRNA expression and the combination of these two. The results revealed that the sensitivity of breast ultrasound BI-RADS classification was 89%, the specificity was 74%, the area under the curve was 0.888(p <0.001); the diagnostic sensitivity of PD-1 mRNA expression was 78%, the specificity was 77%, the area under the curve was 0.826(p<0.001); the combined sensitivity of these two was 91%, the specificity was 87%, and the area under the curve was 0.918(p<0.001). In breast cancer patients, high tumor diameter and stage predicted increased BI-RADS grade; progesterone receptor positive patients showed an increase of PD-1 mRNA expression. This study suggesedthat the diagnostic value of breast ultrasound BI-RADS classification combined with PD-1 detection could superior to the diagnostic value of both, which may be an effective method for the diagnosis of breast cancer and it might worth to use in clinical practice.
引文
Bertucci F.,Finetti P.,Birnbaum D.,and Mamessier E.,2016,Th PD1/PDL1 axis,a promising therapeutic target in aggressiv breast cancers,Oncoimmunology,5(3):e1085148
Chen W.,Zheng R.,Baade P.D.,Zhang S.,Zeng H.,Bray F.,Jema A.,Yu X.Q.,and He J.,2016,Cancer statistics in China2015,CA Cancer J.Clin.,66(2):115-132
Cheuk I.W.,Shin V.Y.,and Kwong A.,2017,Detection of methy lated circulating DNA as noninvasive biomarkers for breas cancer diagnosis,J.Breast Cancer,20(1):12-19
Evans A.,Whelehan P.,Thomson K.,Brauer K.,Jordan L.,Purdi C.,Mc Lean D.,Baker L.,Vinnicombe S.,and Thompson A.2012,Differentiating benign from malignant solid breas masses:value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BI-RADS classification,Br J.Cancer,107(2):224-229
Fan L.,Strasser-Weippl K.,Li J.J.,St Louis J.,Finkelstein D.M.Yu K.D.,Chen W.Q.,Shao Z.M.,and Goss P.E.,2014,Breas cancer in China,Lancet Oncol.,15(7):279-289
Katsuya Y.,Horinouchi H.,Asao T.,Kitahara S.,Goto Y.,Kand S.,Fujiwara Y.,Nokihara H.,Yamamoto N.,Watanabe S.-i.Tsuta K.,and Ohe Y.,2016,Expression of programmed death1(PD-1)and its ligand(PD-L1)in thymic epithelial tumors Impact on treatment efficacy and alteration in expression af ter chemotherapy,Lung Cancer,99:4-10
Lawicki S.,Zajkowska M.,Glazewska E.K.,Bedkowska G.E.,and Szmitkowski M.,2016,Plasma levels and diagnostic utility o VEGF,MMP-9,and TIMP-1 in the diagnosis of patient with breast cancer,Onco.Targets Ther.,9:911-919
Mishra S.,Srivastava A.K.,Suman S.,Kumar V.,and Shukla Y.2015,Circulating mi RNAs revealed as surrogate molecula signatures for the early detection of breast cancer,Cance Lett.,369(1):67-75
Shao J.Y.,and Sun G.P.,2015,Research update on PD-1 and its ligand PD-L1in malignant tumor,J.Int.Oncol.,42(5)358-360
Sun S.,Fei X.,Mao Y.,Wang X.,Garfield D.H.,Huang O.,Wang J.,Yuan F.,Sun L.,Yu Q.,Jin X.,Wang J.,and Shen K.,2014PD-1(+)immune cell infiltration inversely correlates with survival of operable breast cancer patients,Cancer Immuno Immunother,63(4):395-406
Uehiro N.,Sato F.,Pu F.,Tanaka S.,Kawashima M.,Kawaguch K.,Sugimoto M.,Saji S.,and Toi M.,2016,Circulating cell-free DNA-based epigenetic assay can detect early breas cancer,Breast Cancer Res.,18(1):129
Waki K.,Yamada T.,Yoshiyama K.,Terazaki Y.,Sakamoto S.Matsueda S.,Komatsu N.,Sugawara S.,Takamori S.,Itoh K.and Yamada A.,2014,PD-1 expression on peripheral blood T-cell subsets correlates with prognosis in non-small cell lung cancer,Cancer Sci.,105(10):1229-1235
Wu X.M.,Lei Y.,and Duan X.Y.,2017,Research progress o PD-1/PDL1 in ovarian cancer,Yixue Yanjiusheng Xuebao(J.Med.Postgra.),30(1):108-111(伍筱玫,雷月,段晓义2017,程序性死亡受体-1/配体-1在卵巢癌中的研究紧张,医学研究生学报,30(1):108-111)
Xiao X.,Jiang Q.,Wu H.,Guan X.,Qin W.,and Luo B.,2017,Di agnosis of sub-centimetre breast lesions:combining BI-RADS-US with strain elastography and contrast-enhanced ultrasound-a preliminary study in China,Eur.Radiol.,27(6)2443-2450
Ye M.,Huang T.,Ying Y.,Li J.,Yang P.,Ni C.,Zhou C.,and Chen S.,2017,Detection of 14-3-3 sigma(sigma)promoter methy lation as a noninvasive biomarker using blood samples fo breast cancer diagnosis,Oncotarget,8(6):9230-9242
Zhang K.J.,Zhang Y.,Luo Z.L.,Liu L.,Yang J.,Wu L.C.,Yu S.S.and Liu J.B.,2016,Long no n-coding RNA HOTAIR in plasma as a potential biomarker for breast cancer diagnosis Nangfang Yike Daxue Xuebao(Journal of Southern Medi cal University),36(4):488-492(张开炯,张毅,罗正莲,刘恋,杨洁,吴立春,张莉,余思思,刘靳波,2016,血浆长链非编码RNA HOTAIR是乳腺癌诊断的潜在生物标志物南方医科大学学报,36(4):488-492)
Zhang L.,Xu Y.,Jin X.,Wang Z.,Wu Y.,Zhao D.,Chen G.,Li D.Wang X.,Cao H.,Xie Y.,and Lian g Z.,2015,A circulating mi RNA signature as a diagnostic biomarker for non-invasiv early detection of breast cancer,Breast Cancer Res.Treat,154(2):423-434
Zuo X.,Chen L.,Liu L.,Zhang Z.,Zhang X.,Yu Q.,Feng L.,Zhao X.,and Qin T.,2016,Identification of a panel of complex autoantigens(LGALS3,PHB2,MUC1,and GK2)in combination with CA15-3 for the diagnosis of early-stage breast cancer,Tumour Biol.,37(1):1309-1317
Chen W.,Zheng R.,Baade P.D.,Zhang S.,Zeng H.,Bray F.,Jema A.,Yu X.Q.,and He J.,2016,Cancer statistics in China2015,CA Cancer J.Clin.,66(2):115-132
Cheuk I.W.,Shin V.Y.,and Kwong A.,2017,Detection of methy lated circulating DNA as noninvasive biomarkers for breas cancer diagnosis,J.Breast Cancer,20(1):12-19
Evans A.,Whelehan P.,Thomson K.,Brauer K.,Jordan L.,Purdi C.,Mc Lean D.,Baker L.,Vinnicombe S.,and Thompson A.2012,Differentiating benign from malignant solid breas masses:value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BI-RADS classification,Br J.Cancer,107(2):224-229
Fan L.,Strasser-Weippl K.,Li J.J.,St Louis J.,Finkelstein D.M.Yu K.D.,Chen W.Q.,Shao Z.M.,and Goss P.E.,2014,Breas cancer in China,Lancet Oncol.,15(7):279-289
Katsuya Y.,Horinouchi H.,Asao T.,Kitahara S.,Goto Y.,Kand S.,Fujiwara Y.,Nokihara H.,Yamamoto N.,Watanabe S.-i.Tsuta K.,and Ohe Y.,2016,Expression of programmed death1(PD-1)and its ligand(PD-L1)in thymic epithelial tumors Impact on treatment efficacy and alteration in expression af ter chemotherapy,Lung Cancer,99:4-10
Lawicki S.,Zajkowska M.,Glazewska E.K.,Bedkowska G.E.,and Szmitkowski M.,2016,Plasma levels and diagnostic utility o VEGF,MMP-9,and TIMP-1 in the diagnosis of patient with breast cancer,Onco.Targets Ther.,9:911-919
Mishra S.,Srivastava A.K.,Suman S.,Kumar V.,and Shukla Y.2015,Circulating mi RNAs revealed as surrogate molecula signatures for the early detection of breast cancer,Cance Lett.,369(1):67-75
Shao J.Y.,and Sun G.P.,2015,Research update on PD-1 and its ligand PD-L1in malignant tumor,J.Int.Oncol.,42(5)358-360
Sun S.,Fei X.,Mao Y.,Wang X.,Garfield D.H.,Huang O.,Wang J.,Yuan F.,Sun L.,Yu Q.,Jin X.,Wang J.,and Shen K.,2014PD-1(+)immune cell infiltration inversely correlates with survival of operable breast cancer patients,Cancer Immuno Immunother,63(4):395-406
Uehiro N.,Sato F.,Pu F.,Tanaka S.,Kawashima M.,Kawaguch K.,Sugimoto M.,Saji S.,and Toi M.,2016,Circulating cell-free DNA-based epigenetic assay can detect early breas cancer,Breast Cancer Res.,18(1):129
Waki K.,Yamada T.,Yoshiyama K.,Terazaki Y.,Sakamoto S.Matsueda S.,Komatsu N.,Sugawara S.,Takamori S.,Itoh K.and Yamada A.,2014,PD-1 expression on peripheral blood T-cell subsets correlates with prognosis in non-small cell lung cancer,Cancer Sci.,105(10):1229-1235
Wu X.M.,Lei Y.,and Duan X.Y.,2017,Research progress o PD-1/PDL1 in ovarian cancer,Yixue Yanjiusheng Xuebao(J.Med.Postgra.),30(1):108-111(伍筱玫,雷月,段晓义2017,程序性死亡受体-1/配体-1在卵巢癌中的研究紧张,医学研究生学报,30(1):108-111)
Xiao X.,Jiang Q.,Wu H.,Guan X.,Qin W.,and Luo B.,2017,Di agnosis of sub-centimetre breast lesions:combining BI-RADS-US with strain elastography and contrast-enhanced ultrasound-a preliminary study in China,Eur.Radiol.,27(6)2443-2450
Ye M.,Huang T.,Ying Y.,Li J.,Yang P.,Ni C.,Zhou C.,and Chen S.,2017,Detection of 14-3-3 sigma(sigma)promoter methy lation as a noninvasive biomarker using blood samples fo breast cancer diagnosis,Oncotarget,8(6):9230-9242
Zhang K.J.,Zhang Y.,Luo Z.L.,Liu L.,Yang J.,Wu L.C.,Yu S.S.and Liu J.B.,2016,Long no n-coding RNA HOTAIR in plasma as a potential biomarker for breast cancer diagnosis Nangfang Yike Daxue Xuebao(Journal of Southern Medi cal University),36(4):488-492(张开炯,张毅,罗正莲,刘恋,杨洁,吴立春,张莉,余思思,刘靳波,2016,血浆长链非编码RNA HOTAIR是乳腺癌诊断的潜在生物标志物南方医科大学学报,36(4):488-492)
Zhang L.,Xu Y.,Jin X.,Wang Z.,Wu Y.,Zhao D.,Chen G.,Li D.Wang X.,Cao H.,Xie Y.,and Lian g Z.,2015,A circulating mi RNA signature as a diagnostic biomarker for non-invasiv early detection of breast cancer,Breast Cancer Res.Treat,154(2):423-434
Zuo X.,Chen L.,Liu L.,Zhang Z.,Zhang X.,Yu Q.,Feng L.,Zhao X.,and Qin T.,2016,Identification of a panel of complex autoantigens(LGALS3,PHB2,MUC1,and GK2)in combination with CA15-3 for the diagnosis of early-stage breast cancer,Tumour Biol.,37(1):1309-1317