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【Gut】科学家找到肝癌早诊和术后评估新方法
WHO发布的“伤残调整生命年”（DALY）报告显示，肝癌是中国癌症患者的主要死因之一；在各种疾病中，肝癌给中国带来的经济和社会负担排名第一。在中国，肝炎病毒携带者有9300万人，占总人口的7.18%，由乙肝经过肝硬化最终发展为肝癌是中国肝癌患者的经典路径，全球每新增2例肝癌就有1例发生在中国。而早期诊断和治疗肝癌、防治乙肝后肝硬化是我国医学界面临的重要任务。
研究组通过测定肝癌高危人群GP73和AFP的敏感度和特异度，发现GP73对肝癌的敏感度为74.6%、特异度为97.4%；而同一组患者，AFP对肝癌的敏感度和特异度分别为58.2%和85.3%，这提示GP73在肝癌检测的敏感度和特异度上均远高于AFP。
通过肝癌组与健康组的对照，研究组还在国际上首先确立了GP73的正常值为1.2（0.9～1.7）相对单位，肝癌组血清GP73平均值为14.7（8.9～29.4）相对单位，远高于健康对照组，且与肿瘤个体的大小无关。研究组在对肝癌患者术前、术后及随访等的连续观察表明，患者GP73水平随着肿瘤切除而下降，术后14天，该指标跌到谷底。但当肿瘤复发后，GP73也开始反弹。
研究组专家表示，这项研究支持了乙肝病毒感染是肝癌的重要致病原因。大样本数据显示：乙肝病毒携带者和肝硬化患者的GP73值均有一定程度的升高，但一般均小于5相对单位，明显低于肝癌患者。这暗示了GP73在监测患者从携带乙肝病毒发展到肝硬化，最终发展为肝癌的整个疾病进程中的重要意义。
研究组还首次检测了与肝硬化、肝癌无关的胃癌、食道癌、结直肠癌、胰腺癌等14种临床常见癌症的GP73值。结果证实，GP73在其他良性、恶性肿瘤中尽管有轻度升高，但增高值远远低于原发性肝细胞肝癌患者，证实GP73为肝癌的单一肿瘤标记物。
这项研究是北京协和医院肝脏外科联合中国医科院肿瘤医院、江苏启东肝癌研究所和美国芝加哥大学医学中心等单位共同完成的。研究组收集的4217例血清样本涵盖了黄种人、白种人和黑种人等3个种族的各类肝病患者，获得了迄今国际上关于GP73研究的样本量最大、检测项目最全面和最有说服力的数据。此外，协和肝外科还联合中国医科院基础医学研究所成功合成了GP73单克隆抗体，为今后临床推广打下了良好基础。
毛一雷指出，GP73的出现要归因于近年来蛋白组学和分子生物学的进步，而GP73和AFP联合检测可提高肝癌的早期诊断、早期治疗水平。（来源：科学时报 段文利 祝魏玮） Abstract
Background and aims Golgi protein 73 (GP73) as a potential serum marker for hepatocellular carcinoma (HCC) has not been validated in large cohort studies. Furthermore, its significance in the assessment of tumour recurrence after HCC resection remains unknown. The aim of this study was to determine the value of serum GP73 in the diagnosis of HCC.
Methods Serum GP73 and alpha-fetoprotein (AFP) were compared in a total of 4217 human subjects in this multicentre study, including 1690 healthy adults, 337 hepatitis B virus (HBV) carriers, 512 patients with cirrhosis, 789 patients with HCC, 61 patients with other malignant liver lesions, 206 patients with benign liver lesions and 622 patients with 14 different kinds of non-liver cancers. The main outcome measures were the specificity and sensitivity of GP73 in patients at risk for the development of HCC.
Results Using 8.5 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 74.6% (95% CI 71.5% to 77.6%) and 97.4% (95% CI 96.8 to 98.3%), compared with 58.2% (95% CI 55.2% to 62.1%) and 85.3% (95% CI 83.4% to 88.1%) for AFP (p<0.001) using 35 ng/ml as a cut-off value. The GP73 level was significantly increased in patients with HCC compared with healthy controls (14.7 vs 1.2, p<0.001). Although GP73 levels in HBV carriers (2.9) and patients with cirrhosis (4.7) were somewhat elevated, they were much lower than that in patients with HCC (p<0.001). GP73 decreased following surgical resection of HCC lesions and increased with tumour recurrence. Fourteen types of non-liver cancers were analysed; all the benign and other malignant liver lesions had moderate elevations of GP73, albeit at a much lower level than in HCC.
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作者:admin@医学,生命科学 2011-01-28 08:47
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