目的研究血清血管内皮生长因子(VEGF)、p53抗体和AFP联合检测对原发性肝细胞癌(HCC)的诊断价值。方法44例经病理确诊的HCC组患者和46例肝硬化组患者，50名正常对照组，采用ELISA检测血清VEGF和p53抗体，微粒子酶免疫分析法(MEIA)测定血清AFP。结果HCC组血清VEGF水平(444.82ng/L)明显高于肝硬化组(102.32ng/L)和正常对照组(98.13ng/L)(P＜0.05);HCC组血清p53抗体(1.32kU/L水平)明显高于肝硬化组(0.25kU/L)和正常对照组(0.16kU/L)(P＜0.05);HCC组血清VEGF阳性率(61.36%)和p53抗体阳性率(22.73%)高于肝硬化组(8.70%)和正常对照组(2.17%)(P＜0.05)。血清VEGF与HCC病灶大小、PVI浸润有关，而与AFP水平、HBV感染无相关;血清p53抗体与AFP、HCC病灶大小、PVI浸润和HBV感染均无相关。VEGF或p53抗体诊断HCC的敏感性(81.82%，77.27%)，AFP(65.91%);三项联合检测均优于单项AFP;无论VEGF和p53抗体水平都与AFP水平无相关，但在AFP阴性HCC病例中VEGF的阳性率为46.67%，p53抗体的阳性率为33.33%。结论VEGF和p53抗体可作新的肿瘤标志物，提高AFP对HCC的潜在诊断效能。
Objective To explore the clinical diagnostic values of combined detection of serum p53 Abs, VEGF and AFP in patients with HCC. Methods 44 patients with HCC, 46 patients with liver cirrhosis and 50 healthy controls were involved in this study. The serum p53 Abs and VEGF levels were examined for by ELISA and the serum AFP levels were detected by MEIA. Results The serum levels of VEGF and p53 Abs in HCC patients were significantly higher than that in cirrhotic patients and control group (P＜ 0.05). The positive rate of VEGF and p53 Abs (61.36%, 22.73%) in HCC patients were also higher than that in liver cirrhosis (8.70%,2.17%) and healthy controls (P＜ 0.05). The serum VEGF expression was related with the size of HCC, PVI, while was not related with AFP levels and the infection of HBV. The p53 Abs expression was independent of the size of HCC, PVI, and AFP levels and the infection of HBV. The sensitivity of combined measurement of VEGF or p53 Abs and AFP was better than that AFP alone. There was no correlation between either p53 Abs or VEGF and AFP levels. However, the positive rate of VEGF and p53 Abs were 46.67% and 33.33% respectively in AFP negative patients with HCC. Conclusion The serum VEGF and p53 Abs may be considered as additional tumor markers to increase the diagnostic values of AFP in patients with HCC.
[1] Wright L M, Kreikemeier J T, Fimmel C J. A concise review of serum markers for hepatocellular cancer[J]. Cancer Detect Prev, 2007, 31(1):35-44.
[2] Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma [J].World J Gastroenterol, 2006,12(8): 1175-1181.
[3] Ahmed O K, Amr H, Mattew C, et al. Vascular endothelial growth factor in the management of hepatocellular carcinoma[J]. Cancer, 2009, 11(1):4895-4906.
[4] Soresi M, Magliarisi C, Campagna P, et al. Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma [J]. Anticancer Res, 2003, 23(2C):1747-1753.
[5] Yang B H, Xia J L, Huang L W, et al. Changes of clinical aspect of primary liver cancer in China during the past 30 years--control study for 3,250 cases with primary liver cancer[J]. Zhonghua Yi Xue Za Zhi, 2003, 83(12):1053-1057.
[6] Huang G W, Yang L Y, Lu W Q. Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factorin hepatocellular carcinoma: Impact on neovascularization and survival[J]. World J Gastroenterol, 2005, 11: 1705-1708.
[7] Kim S J, Choi I K, Park K H, et al. Serum vascular endothelial growth factor per platelet count in hepatocellular carcinoma: correlations with clinical parameters and survival[J]. Jpn J Clin Oncol, 2004, 34: 184-190.
[8] Kamel L, Nessim I, Abd-el-Hady A, et al. Assessment of the clinical significance of serum vascular endothelial growth factor and matrix metalloproteinase-9 in patients with hepatocellular carcinoma[J]. J Egypt Soc Parasitol, 2005; 35:875-890.
[9] Chang S C, Lin J K, Lin T C, et al. Genetic alternation of p53, but not overexpression of intratumoral p53 protein, or p53 antibody is a prognostic factor in hepatocellular carcinoma[J]. Int J Clin Oncol, 2005, 26:65-75.
[10] Charuruks N, Tangkijvanich P, Voravud N, et al. Clinical significance of p53 antigen and anti-p53 antibodies in the sera of hepatocellular carcinoma patients[J]. J Gastroenterol, 2001, 36:830-836.
