肝细胞癌和肝硬化与全球的高死亡率相关。目前，甲胎蛋白被用来作为肝细胞癌检测的标准血清标志物，但其灵敏度和特异性并不能令人满意，肝硬化的最佳诊断标志物仍是缺乏的。我们曾经报道生长分化因子15在丙型肝炎病毒感染的肝细胞中被显著诱导。
本研究旨在探讨GDF15表达及其与肝炎病毒相关的肝脏疾病的相关性。研究纳入412例各种肝脏疾病的患者。健康者和结核杆菌感染者作为对照被纳入。研究对血清和组织GDF15水平进行了测定。肝癌患者组（6.66±0.67ng/ml，P <0.0001）和肝硬化组（6.51±1.47ng/ml，P <0.0001）血清GDF15水平较健康对照组（0.31±0.01ng/ml）显著升高，尽管其在HBV和HCV携带者中GDF15水平中度升高（分别为1.34±0.19 ng / mL和2.13±0.53ng/ml）。与乙型肝炎病毒或丙型肝炎病毒携带者相比，在肝硬化或肝细胞癌患者中GDF15临界值为2.463 ng / mL时的敏感性为63.1％、特异性为86.6％。在肝癌患者中，GDF15与AFP的ROC曲线下面积分别为0.84和0.76，但GDF15和AFP结合时为0.91。血清GDF15水平在高AFP和低AFP不同群体之间没有显著差异。
在肝细胞癌GDF15表达明显高于相应临近的癌旁组织和正常肝脏。利用GDF15和AFP组合会提高肝细胞癌诊断的敏感性和特异性。血清GDF15测量的进一步的研究和临床实践建议将其作为肝癌和肝硬化的生物标志物。
本文首次发表于[PLoS One，2015，10(5)：e0127518]
Association of Serum Level of Growth Differentiation Factor 15 with Liver Cirrhosis and Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) and liver cirrhosis are associated with high mortality worldwide. Currently, alpha-fetoprotein (AFP) is used as a standard serum marker for the detection of HCC, but its sensitivity and specificity are unsatisfactory, and optimal diagnostic markers for cirrhosis are lacking. We previously reported that growth differentiation factor 15 (GDF15) was significantly induced in HCV-infected hepatocytes. This study aimed to investigate GDF15 expression and its correlation with hepatitis virus-related liver diseases. A total of 412 patients with various liver diseases were studied. Healthy and Mycobacterium tuberculosis-infected subjects were included as controls. Serum and tissue GDF15 levels were measured.Serum GDF15 levels were significantly increased in patients with HCC (6.66±0.67 ng/mL, p<0.0001) and cirrhosis (6.51±1.47 ng/mL, p<0.0001) compared with healthy controls (0.31±0.01 ng/mL), though the GDF15 levels in HBV and HCV carriers were moderately elevated (1.34±0.19 ng/mL and 2.13±0.53 ng/mL, respectively). Compared with HBV or HCV carriers, GDF15 had a sensitivity of 63.1% and a specificity of 86.6% at the optimal cut-off point of 2.463 ng/mL in patients with liver cirrhosis or HCC. In HCC patients, the area under the receiver operating curve was 0.84 for GDF15 and 0.76 for AFP, but 0.91 for the combined GDF15 and AFP. Serum GDF15 levels did not significantly differ between the high-AFP and low-AFP groups. GDF15 protein expression in HCC was significantly higher than that in the corresponding adjacent paracarcinomatous tissue and normal liver. Using a combination of GDF15 and AFP will improve the sensitivity and specificity of HCC diagnosis. Further research and the clinical implementation of serum GDF15 measurement as a biomarker for HCC and cirrhosis are recommended.
