肝細(xì)胞癌和肝硬化與全球的高死亡率相關(guān)。目前，甲胎蛋白被用來(lái)作為肝細(xì)胞癌檢測(cè)的標(biāo)準(zhǔn)血清標(biāo)志物，但其靈敏度和特異性并不能令人滿意，肝硬化的最佳診斷標(biāo)志物仍是缺乏的。我們?cè)?jīng)報(bào)道生長(zhǎng)分化因子15在丙型肝炎病毒感染的肝細(xì)胞中被顯著誘導(dǎo)。
本研究旨在探討GDF15表達(dá)及其與肝炎病毒相關(guān)的肝臟疾病的相關(guān)性。研究納入412例各種肝臟疾病的患者。健康者和結(jié)核桿菌感染者作為對(duì)照被納入。研究對(duì)血清和組織GDF15水平進(jìn)行了測(cè)定。肝癌患者組（6.66±0.67ng/ml，P <0.0001）和肝硬化組（6.51±1.47ng/ml，P <0.0001）血清GDF15水平較健康對(duì)照組（0.31±0.01ng/ml）顯著升高，盡管其在HBV和HCV攜帶者中GDF15水平中度升高（分別為1.34±0.19 ng / mL和2.13±0.53ng/ml）。與乙型肝炎病毒或丙型肝炎病毒攜帶者相比，在肝硬化或肝細(xì)胞癌患者中GDF15臨界值為2.463 ng / mL時(shí)的敏感性為63.1％、特異性為86.6％。在肝癌患者中，GDF15與AFP的ROC曲線下面積分別為0.84和0.76，但GDF15和AFP結(jié)合時(shí)為0.91。血清GDF15水平在高AFP和低AFP不同群體之間沒(méi)有顯著差異。
在肝細(xì)胞癌GDF15表達(dá)明顯高于相應(yīng)臨近的癌旁組織和正常肝臟。利用GDF15和AFP組合會(huì)提高肝細(xì)胞癌診斷的敏感性和特異性。血清GDF15測(cè)量的進(jìn)一步的研究和臨床實(shí)踐建議將其作為肝癌和肝硬化的生物標(biāo)志物。
本文首次發(fā)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.
