CAJ | 학술논문

目的探讨巨噬细胞移动抑制因子(MIF)在肝癌诊断中的价值.方法试验分为测试研究和验证研究.回顾性分析2004年1月至5月复旦大学附属中山医院收治的269例肝癌患者(测试肝癌组)和390例对照人群(测试对照组)；8月至12月收治的173例肝癌患者(验证肝癌组)和257例对照人群(验证对照组)；2005年1月收治的80例行根治性肝切除的肝癌患者的临床资料.收集测试研究和验证研究受试者术前体格检查的血浆标本和行根治性肝切除的肝癌患者术前、术后3、7、30 d的血浆标本,同时收集测试肝癌组患者术后的肝癌组织和癌旁(距肿瘤1cm)组织标本.采用ELISA法检测血浆中MIF水平,免疫组织化学法检测组织中MIF表达情况.非正态分布数据用中位数(四分位数间距)[M(QR)]表示,组间比较采用Mann-Whitney U检验,血浆和组织中MIF的关系采用Spearman相关分析,ROC曲线分析MIF的诊断价值.结果在测试研究中,测试肝癌组和测试对照组受试者血浆MIF中位值分别为85.7 μg/L(58.8 μg/L)和15.5 μg/L(31.6 μg/L).其中测试对照组中的肝硬化患者、良性肝病患者和健康体检者血浆MIF中位值分别为24.9 μg/L( 12.6 μg/L)、12.5 μg/L(7.3μg/L)、13.2 μg/L(7.7 μg/L),两组各受试者血浆MIF比较,差异有统计学意义(F=54.235,P＜0.05).ROC曲线结果表明,当血浆MIF为35.3 μg/L时,可获得最大的曲线下面积.验证肝癌组与验证对照组比较,AUC值、灵敏度、特异度分别为92.1％、90.7％、93.4％.肝癌患者术前和术后3、7、30 d血浆MIF中位值分别为81.0μg/L(54.0μg/L)、76.1 μg/L(47.5 μg/L)、50.9 μg/L(40.7 μg/L)、18.7μg/L(15.1 μg/L),呈时间依赖性降低,术后30 d基本恢复到正常范围内.肝癌组织和癌旁组织MIF的中位表达强度分别为0.083和0.007,两者比较,差异有统计学意义(U=3.975,P＜0.05).肝癌患者血浆中MIF和相应的肝癌组织内MIF表达呈正相关(r=0.759,P＜0.05).结论 MIF与肝癌发生、发展密切相关,MIF可作为肝癌诊断的潜在分子标志物. 目的探討巨噬細胞移動抑製因子(MIF)在肝癌診斷中的價值.方法試驗分為測試研究和驗證研究.迴顧性分析2004年1月至5月複旦大學附屬中山醫院收治的269例肝癌患者(測試肝癌組)和390例對照人群(測試對照組)；8月至12月收治的173例肝癌患者(驗證肝癌組)和257例對照人群(驗證對照組)；2005年1月收治的80例行根治性肝切除的肝癌患者的臨床資料.收集測試研究和驗證研究受試者術前體格檢查的血漿標本和行根治性肝切除的肝癌患者術前、術後3、7、30 d的血漿標本,同時收集測試肝癌組患者術後的肝癌組織和癌徬(距腫瘤1cm)組織標本.採用ELISA法檢測血漿中MIF水平,免疫組織化學法檢測組織中MIF錶達情況.非正態分佈數據用中位數(四分位數間距)[M(QR)]錶示,組間比較採用Mann-Whitney U檢驗,血漿和組織中MIF的關繫採用Spearman相關分析,ROC麯線分析MIF的診斷價值.結果在測試研究中,測試肝癌組和測試對照組受試者血漿MIF中位值分彆為85.7 μg/L(58.8 μg/L)和15.5 μg/L(31.6 μg/L).其中測試對照組中的肝硬化患者、良性肝病患者和健康體檢者血漿MIF中位值分彆為24.9 μg/L( 12.6 μg/L)、12.5 μg/L(7.3μg/L)、13.2 μg/L(7.7 μg/L),兩組各受試者血漿MIF比較,差異有統計學意義(F=54.235,P＜0.05).ROC麯線結果錶明,噹血漿MIF為35.3 μg/L時,可穫得最大的麯線下麵積.驗證肝癌組與驗證對照組比較,AUC值、靈敏度、特異度分彆為92.1％、90.7％、93.4％.肝癌患者術前和術後3、7、30 d血漿MIF中位值分彆為81.0μg/L(54.0μg/L)、76.1 μg/L(47.5 μg/L)、50.9 μg/L(40.7 μg/L)、18.7μg/L(15.1 μg/L),呈時間依賴性降低,術後30 d基本恢複到正常範圍內.肝癌組織和癌徬組織MIF的中位錶達彊度分彆為0.083和0.007,兩者比較,差異有統計學意義(U=3.975,P＜0.05).肝癌患者血漿中MIF和相應的肝癌組織內MIF錶達呈正相關(r=0.759,P＜0.05).結論 MIF與肝癌髮生、髮展密切相關,MIF可作為肝癌診斷的潛在分子標誌物.
목적 탐토거서세포이동억제인자(MIF)재간암진단중적개치.방법 시험분위측시연구화험증연구.회고성분석2004년1월지5월복단대학부속중산의원수치적269례간암환자(측시간암조)화390례대조인군(측시대조조)；8월지12월수치적173례간암환자(험증간암조)화257례대조인군(험증대조조)；2005년1월수치적80례행근치성간절제적간암환자적림상자료.수집측시연구화험증연구수시자술전체격검사적혈장표본화행근치성간절제적간암환자술전、술후3、7、30 d적혈장표본,동시수집측시간암조환자술후적간암조직화암방(거종류1cm)조직표본.채용ELISA법검측혈장중MIF수평,면역조직화학법검측조직중MIF표체정황.비정태분포수거용중위수(사분위수간거)[M(QR)]표시,조간비교채용Mann-Whitney U검험,혈장화조직중MIF적관계채용Spearman상관분석,ROC곡선분석MIF적진단개치.결과 재측시연구중,측시간암조화측시대조조수시자혈장MIF중위치분별위85.7 μg/L(58.8 μg/L)화15.5 μg/L(31.6 μg/L).기중측시대조조중적간경화환자、량성간병환자화건강체검자혈장MIF중위치분별위24.9 μg/L( 12.6 μg/L)、12.5 μg/L(7.3μg/L)、13.2 μg/L(7.7 μg/L),량조각수시자혈장MIF비교,차이유통계학의의(F=54.235,P＜0.05).ROC곡선결과표명,당혈장MIF위35.3 μg/L시,가획득최대적곡선하면적.험증간암조여험증대조조비교,AUC치、령민도、특이도분별위92.1％、90.7％、93.4％.간암환자술전화술후3、7、30 d혈장MIF중위치분별위81.0μg/L(54.0μg/L)、76.1 μg/L(47.5 μg/L)、50.9 μg/L(40.7 μg/L)、18.7μg/L(15.1 μg/L),정시간의뢰성강저,술후30 d기본회복도정상범위내.간암조직화암방조직MIF적중위표체강도분별위0.083화0.007,량자비교,차이유통계학의의(U=3.975,P＜0.05).간암환자혈장중MIF화상응적간암조직내MIF표체정정상관(r=0.759,P＜0.05).결론 MIF여간암발생、발전밀절상관,MIF가작위간암진단적잠재분자표지물.
Objective To investigate the diagnostic value of macrophage migration inhibitory factor (MIF) for hepatocellular carcinoma (HCC).Methods The research was divided into 2 parts,including testing research and confirmatory research.The clinical data of 269 patients with HCC ( group A) and 390 individuals (including 135 patients with hepatic cirrhosis,106 with benign hepatic diseases and 149 healthy individuals,control group A) who were admitted to the Zhongshan Hospital of Fudan University from January to May,2004,and 173 patients with hepatic cancer (group B) and 257 individuals (including 86 patients with hepatic cirrhosis,79 with benign hepatic diseases and 92 healthy individuals,control group B ) who were admitted from August to December,2004,and 80 patients with HCC who received radical hepatic resection in January 2005 were retrospectively analyzed.Samples of plasma of patients in the group A and individuals in the control group A were collected before operation.Samples of plasma of patients received radical hepatic resection were collected preoperatively and at postoperative day 3,7 and 30.HCC and adjacent issues of patients in the group A were collected.The levels of MIF in the plasma and tissues were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry,respectively.Non-normal distribution data were described as M( QR).Differences between the groups were analyzed by using the Mann-Whitney U test,and the relationship between the levels of MIF in the plasma and tissues was detected by the Spearman correlation coefficient.The diagnostic value of MIF was analyzed by the ROC curve.Results The levels of MIF in the plasma of patients in the group A and individuals in the control group A were 85.7 μg/L (58.8 μg/L) and 15.5 μg/L(31.6 μg/L),respectively.The levels of MIF in the plasma of the patients with hepatic cirrhosis,benign hepatic diseases and healthy individuals were 24.9 μg/L (12.6 μg/L),12.5 μg/L(7.3 μg/L) and 13.2 μg/L (7.7 μg/L),respectively.There was a significant difference in the level of MIF between the group A and the control group A (F =54.235,P ＜ 0.05 ).The area under the ROC curve reached peak when the level of MIF in the plasma was 35.3μg/L.Compared with the control group B,the vdues of AUC,sensitivity and specificity were 92.1％,90.7％ and 93.4％ in the group B.The levels of MIF of the patients with HCC before operation and at 3,7,and 30 days after operation were 81.0 μg/L(54.0 μg/L),76.1 μg/L(47.5 μg/L),50.9 μg/L (40.7 μg/L) and 18.7 μg/L ( 15.1 μg/L),respectively.The levels of MIF decreased with time passed by,and were back to normal at 30 days after the operation.The median expressions of MIF in the HCC and adjacent issues were 0.083 and 0.007,respectively,with a significant difference ( U =3.975,P ＜ 0.05).The expression of MIF in the plasma was positively correlated with its expression in the HCC tissue ( r =0.759,P ＜ 0.05 ).Conclusion MIF plays an important role in the genesis and development of HCC and has potential to be one of the molecular markers for the diagnosis of HCC.