CAJ | 학술논문

目的筛选与肝癌患者肝移植术后肿瘤复发相关的术前血清生物标记物,并建立肿瘤复发的预测模型.方法 76例受者被纳入本项研究,其中35例术后发生肿瘤复发和转移(复发组),其余41例均无瘤存活(无瘤存活组).移植前收集受者血清,采用表面加强激光解吸电离-飞行时间质谱(SELDI-TOF-MS)技术获取受者的蛋白质指纹图谱,利用"生物标记物向导"软件对两组受者间的蛋白峰进行比较.随机选择60例受者(复发组30例,无瘤存活组30例)的血清蛋白指纹图谱作为建模组,通过"生物标记物模型"软件(BPS)建立预测模型.取另外16例(复发组5例,无瘤存活组11例)受者的血清蛋白指纹图谱作为验证组,采用盲法验证该模型的灵敏性和特异性.结果复发组和无瘤存活组受者的临床资料及病理特征间仅术前肿瘤大小和血管侵犯程度的比较,差异有统计学意义(P＜0.05).建立血清蛋白质指纹图谱后,在质荷比(M/Z)2000～3000范围内,共检测出368个蛋白峰,两组间有显著差异的蛋白峰共有22个,其中9个在复发组中表达上调,13个表达下调.通过对原始图谱的初步判断及利用建模组受者上述22个有显著差异的蛋白质,建立决策树预测模型,该模型可以显著地将复发组和无瘤存活组受者区分开.将16例验证组受者的血清蛋白指纹图谱代入决策树预测模型,验证结果显示,5例复发组受者中肿瘤复发4例,无瘤存活1例;11例无瘤存活组受者中无瘤存活受者8例,肿瘤复发3例.该模型的灵敏性为80.0%(4/5),特异性为72.7%(8/11).结论由SELDI-TOF-MS筛选出的血清差异蛋白质可作为肝癌患者肝移植术后肿瘤复发相关的生物标记物,决策树预测模型对肝癌患者接受肝移植的适应证、有无肝外微小转外灶及制定肝移植诊疗计划具有一定临床指导意义.
목적 사선여간암환자간이식술후종류복발상관적술전혈청생물표기물,병건립종류복발적예측모형.방법 76례수자피납입본항연구,기중35례술후발생종류복발화전이(복발조),기여41례균무류존활(무류존활조).이식전수집수자혈청,채용표면가강격광해흡전리-비행시간질보(SELDI-TOF-MS)기술획취수자적단백질지문도보,이용"생물표기물향도"연건대량조수자간적단백봉진행비교.수궤선택60례수자(복발조30례,무류존활조30례)적혈청단백지문도보작위건모조,통과"생물표기물모형"연건(BPS)건립예측모형.취령외16례(복발조5례,무류존활조11례)수자적혈청단백지문도보작위험증조,채용맹법험증해모형적령민성화특이성.결과 복발조화무류존활조수자적림상자료급병리특정간부술전종류대소화혈관침범정도적비교,차이유통계학의의(P＜0.05).건립혈청단백질지문도보후,재질하비(M/Z)2000～3000범위내,공검측출368개단백봉,량조간유현저차이적단백봉공유22개,기중9개재복발조중표체상조,13개표체하조.통과대원시도보적초보판단급이용건모조수자상술22개유현저차이적단백질,건립결책수예측모형,해모형가이현저지장복발조화무류존활조수자구분개.장16례험증조수자적혈청단백지문도보대입결책수예측모형,험증결과현시,5례복발조수자중종류복발4례,무류존활1례;11례무류존활조수자중무류존활수자8례,종류복발3례.해모형적령민성위80.0%(4/5),특이성위72.7%(8/11).결론 유SELDI-TOF-MS사선출적혈청차이단백질가작위간암환자간이식술후종류복발상관적생물표기물,결책수예측모형대간암환자접수간이식적괄응증、유무간외미소전외조급제정간이식진료계화구유일정림상지도의의.
Objective To appraise and compare protein expression profiles in sera of patients without or with recurrence following liver transplantation for hepatocellular carcinoma (HCC) using SELDI-TOF-MS technique,and establish the diagnostic and predictive model. Methods A total of 76 sera (41 from disease free survival patients and 35 from recurrence individuals) were collected pretransplantation and differentially expressed proteins were identified by SELDI-TOF-MS. The intensity values for each peak were analyzed by Biomarker Wizard Software to screen serum proteome biomarkers related to the recurrence post-transplantation. By using Biomarker Patterns Software, the classification trees were generate. from randomly selected samples (30 fingerprints obtained from each group). The sensitivity and specificity of best decision tree were then chosen for blind test with 16 samples (5 from recurrence individuals and 11 from recurrence-free survival patients). Results There were significant differences only in tumor size and the presence of vascular invasion between recurrence group and recurrence-free survival group (P＜0.05). According to serum protein fingerprints, a total of 368 protein peaks were identified at the mass-to-charge ratio (M/Z) value ranging from 2000 to 300 00. There were 22 significant differential proteins between two groups. Among them, 9 proteins were up-regulated and 13 proteins were down-regulated -espectively in recurrence group. The intensity values of differential proteins were input into BPS for classification tree analysis and the best performing tree could distinguish two groups successfully. As a result of blind assessment for this model,a sensitivity of 80.0 % (4/5) and specificity of 72.7 % (8/11) were obtained. Conclusion Some of differential proteins screened by SELDI-TOF-MS technique in the serum may be correlated with the prognoses of liver transplantation patients with HCC. The decision tree may be useful for the clinical application of formulating the indication for liver transplantation, detecting extrahepatic micrometastasis and setting up the diagnostic and treatment strategies.