血清类胰岛素样生长因子结合蛋白-3在肝癌早期复发中的预测价值
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摘要
目的探讨血清类胰岛素样生长因子结合蛋白-3(IGFBP-3)在肝癌早期复发中的预测价值。方法以2013年1月1日至2013年7月2日在浙江大学附属第一医院进行外科切除术的肝癌患者144例为研究对象,术后至少随访12个月。招募体检健康者56例作为健康人对照组。收集研究对象临床资料并检测患者术前和健康人对照组血清IGFBP-3水平。通过ROC曲线分析血清IGFBP-3水平预测肝癌早期复发的效能。通过Kaplane-Meier生存曲线比较各亚组的累计复发率。结果患者随访中位数时间为17.9个月,早期(12个月内)肝癌复发患者50例。肝癌患者组血清IGFBP-3水平显著低于健康人对照组(t=19.70,P<0.01);微血管侵犯(OR=2.498,P<0.05)和术前低水平IGFBP-3(≤1.46 mg/L)(OR=0.454,P<0.05)是肝癌早期复发的独立风险因素。联合IGFBP-3和血管侵犯可以使ROC曲线下面积提高至0.785,敏感性和特异性分别提高至76.0%和75.5%。其诊断能力高于IGFBP-3(Z=3.175,P<0.05)和血管侵犯(Z=2.169,P<0.05)单独使用。此外,低水平的IGFBP-3(57.1%vs 19.8%,P<0.05)和微血管侵犯(48.4%vs 24.4%,P<0.05)与更高的累计复发率有关。结论手术前低水平的IGFBP-3是肝癌早期复发的独立风险因素,联合微血管侵犯这一病理指标,可以提高对肝癌早期复发的预测。
Objective To explore the predictive value of serum insulin-like growth factor binding protein-3( IGFBP-3) levels in early recurrence( ER) after resection for hepatocelluar cancer( HCC). Methods A total of 144 HCC patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine during January 1 and July 2,2013 were enrolled in our study. They were performed hepatectomy,and followed up at least 12 months. In the meanwhile,56 persons with matched age and gender and performed health examination were used as the control. Their clinical data were collected and serum IGFBP-3 levels were determined. Receiver operating characteristic( ROC) curve was used to analyze the predictive potential of serum IGFBP-3 levels on ER after hepatectomy.Kaplan-Meier survival curve was used to compare the cumulative recurrence rates in different subgroups. Results The median followup time for 144 HCC patients was 17. 9 months,and during the first 12 months,50 experienced ER. The serum IGFBP-3 levels in HCC patients were significantly lower than that in healthy controls( t = 19. 70,P < 0. 01). Univariate and multivariate analysis showed that microscopic vascular invasion( MVI)( OR = 2. 498,P < 0. 05) and preoperative low IGFBP-3 levels( ≤1. 46 mg/L)( OR =0. 454,P < 0. 05) were the independent risk factors for ER. When the two risk factors were combined,the AUCROCreached to 0. 785;and sensitivity and specificity increased to 76. 0% and 75. 5%,respectively,which were significantly higher than that in IGFBP-3( Z = 3. 175,P < 0. 05) or MVI( Z = 2. 169,P < 0. 05) alone. Moreover,low IGFBP-3 levels( 57. 1% vs 19. 8%,P < 0. 05) and MVI( 48. 4% vs 24. 4%,P < 0. 05) were significantly related to higher cumulative ER rates. Conclusion Preoperative low IGFBP-3level is an independent risk factor of ER in HCC patients,and may enhance the predictive potential of ER after hepatectomy when combining with MVI.
Objective To explore the predictive value of serum insulin-like growth factor binding protein-3( IGFBP-3) levels in early recurrence( ER) after resection for hepatocelluar cancer( HCC). Methods A total of 144 HCC patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine during January 1 and July 2,2013 were enrolled in our study. They were performed hepatectomy,and followed up at least 12 months. In the meanwhile,56 persons with matched age and gender and performed health examination were used as the control. Their clinical data were collected and serum IGFBP-3 levels were determined. Receiver operating characteristic( ROC) curve was used to analyze the predictive potential of serum IGFBP-3 levels on ER after hepatectomy.Kaplan-Meier survival curve was used to compare the cumulative recurrence rates in different subgroups. Results The median followup time for 144 HCC patients was 17. 9 months,and during the first 12 months,50 experienced ER. The serum IGFBP-3 levels in HCC patients were significantly lower than that in healthy controls( t = 19. 70,P < 0. 01). Univariate and multivariate analysis showed that microscopic vascular invasion( MVI)( OR = 2. 498,P < 0. 05) and preoperative low IGFBP-3 levels( ≤1. 46 mg/L)( OR =0. 454,P < 0. 05) were the independent risk factors for ER. When the two risk factors were combined,the AUCROCreached to 0. 785;and sensitivity and specificity increased to 76. 0% and 75. 5%,respectively,which were significantly higher than that in IGFBP-3( Z = 3. 175,P < 0. 05) or MVI( Z = 2. 169,P < 0. 05) alone. Moreover,low IGFBP-3 levels( 57. 1% vs 19. 8%,P < 0. 05) and MVI( 48. 4% vs 24. 4%,P < 0. 05) were significantly related to higher cumulative ER rates. Conclusion Preoperative low IGFBP-3level is an independent risk factor of ER in HCC patients,and may enhance the predictive potential of ER after hepatectomy when combining with MVI.
引文
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[2]Pivonello C,De Martino MC,Negri M,et al.The GH-IGF-SST system in hepatocellular carcinoma:biological and molecular pathogenetic mechanisms and therapeutic targets[J].Infect Agent Cancer,2014,9:27.
[3]Rehem RN,El-Shikh WM.Serum IGF-1,IGF-2 and IGFBP-3 as parameters in the assessment of liver dysfunction in patients with hepatic cirrhosis and in the diagnosis of hepatocellular carcinoma[J].Hepatogastroenterology,2011,58(107-108):949-954.
[4]Aishima S,Basaki Y,Oda Y,et al.High expression of insulin-like growth factor binding protein-3 is correlated with lower portal invasion and better prognosis in human hepatocellular carcinoma[J].Cancer Sci,2006,97(11):1182-1190.
[5]中华人民共和国卫生部.原发性肝癌诊疗规范(2011年版)[J].临床肿瘤学杂志,2011,16(10):929-946.
[6]Aleem E,Elshayeb A,Elhabachi N,et al.Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection[J].Oncol Lett,2012,3(3):704-712.
[7]Correa CG,Colombo Bda S,Ronsoni MF,et al.Circulating insulinlike growth factor-binding protein 3 as prognostic biomarker in liver cirrhosis[J].World J Hepatol,2016,8(17):739-748.
[8]Liu G,Wang K,Li J,et al.Changes in serum alpha fetoprotein in patients with recurrent hepatocellular carcinoma following hepatectomy[J].J Gastroenterol Hepatol,2015,30(9):1405-1411.
[9]Shah SA,Greig PD,Gallinger S,et al.Factors associated with early recurrence after resection for hepatocellular carcinoma and outcomes[J].J Am Coll Surg,2006,202(2):275-283.
[10]Imamura H,Matsuyama Y,Tanaka E,et al.Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy[J].J Hepatol,2003,38(2):200-207.
[11]Cheng Z,Yang P,Qu S,et al.Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection[J].HPB(Oxford),2015,17(5):422-427.
[12]Omata M,Lesmana LA,Tateishi R,et al.Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma[J].Hepatol Int,2010,4(2):439-474.