妊娠合并宫颈癌中唾液内源性磷酸化肽段的诊断价值

Diagnostic value of salivary endogenous phosphopeptides in cervical cancer in pregnancy

目的研究唾液内源性磷酸化肽段在妊娠合并宫颈癌中的诊断价值,筛选出可能的诊断标志物。方法选择2016年至2018年在武警福建省总队医院、上海第一妇婴和福建省人民医院接受妊娠合并宫颈癌检查的36例患者,按临床分期分为Ⅰ期组12例、Ⅱ期组13例、Ⅲ期组11例,同期在武警福建总队医院妇产科生产的健康孕妇38例作为健康孕妇组。使用唾液采集管分别采集每位健康孕妇和患者的唾液。使用磷酸化肽段富集试剂盒处理唾液样品,得到含内源性磷酸化肽段的洗脱液。使用质谱仪分析洗脱液样品中内源性磷酸化肽段的种类及丰度。结果在全部74例受试者的唾液样品中,共鉴定到25条内源性磷酸化肽段。其中,健康孕妇唾液中鉴定到22条(88%,22/25),Ⅰ期妊娠合并宫颈癌患者唾液中鉴定到20条(80%,20/25),Ⅱ期患者唾液中鉴定到21条(84%,21/25),Ⅲ期患者唾液中鉴定到19条(76%,19/25)。15条(60%,15/25)唾液磷酸化肽段的丰度在健康孕妇和妊娠合并宫颈癌患者之间差异有统计学意义(P<0.05)。共有11条唾液内源性磷酸肽段(44%,11/25)是潜在的妊娠合并宫颈癌诊断标志物,其质荷比(m/z)分别为1076.4、1230.3、1270.3、1461.4、1589.4、1784.6、2004.7、2119.7、2323.7、2541.8、2722.8。其中,质荷比为2119.7的唾液内源性磷酸化肽段对Ⅰ期妊娠合并宫颈癌患者的诊断准确率最高,可达66%。结论根据特定唾液内源性磷酸化肽段的丰度可以在一定程度上区分健康和Ⅰ~Ⅲ期妊娠合并宫颈癌患者,唾液内源性磷酸化肽段具有早期诊断妊娠合并宫颈癌的价值。

Objective To study the diagnostic value of salivary endogenous phosphopeptides among cervical cancer in pregnancy,and to screen out possible diagnostic markers.Methods A total of 36 women cases who had cervical cancer in pregnancy(12 cases assigned to stage Ⅰ,13 cases to stage Ⅱ and 11 cases to stage Ⅲ) during 2016 and 2018 from Shanghai First Maternity and Infant Hospital and Fujian Provincial People’s Hospital was enrolled.And 38 healthy pregnant women who gave birth in the department of Obstetrics and Gynecology of Fujian Armed Police Hospital in the same years were taken as healthy cases.Saliva of each healthy pregnant woman and patients were collected by saliva collection tubes.Saliva samples were treated with phosphopeptide enrichment kits to obtain eluent containing salivary endogenous phosphopeptides.Elution samples were analyzed by MALDI-TOF/TOF mass spectrometry.Quantitative and qualitative results of phosphopeptides were obtained.Results A total of 25 endogenous phosphopeptides was identified in saliva samples from all 74 volunteers.Among them,22 phosphopeptides(88%,22/25) were identified from healthy pregnant women,20 phosphopeptides(80%,20/25) were identified from stage Ⅰ of cervical cancer in pregnancy, 21 phosphopeptides(84%,21/25) were identified from stage Ⅱ,and19 phosphopeptides(76%,19/25) were identified from stage Ⅲ.There were 15(60%,15/25) endogenous phosphopeptides that had significant difference(P<0.05) between healthy pregnant women and cervical cancer in pregnancy.There were 11 phosphopeptides(44%,11/25) are potential diagnostic markers of cervical cancer in pregnancy.Their m/z were 1076.4,1230.3,1270.3,1461.4,1589.4,1784.6,2004.7,2119.7,2323.7,2541.8 and 2722.8,respectively.Among those phosphopeptides,the phosphopeptide 2119.7 had the highest accuracy in differentiating cancer clinical stage Ⅰ(66%).Conclusion Based on the abundance of specific salivary endogenous phosphopeptides could to a certain extent,to distinguish among healthy and Ⅰ-Ⅲ stage cervical cancer in pregnancy.It demonstrated that the salivary endogenous phosphopeptides had the ability of early diagnosis of cervical cancer in pregnancy.