Plasma protein biomarkers of hepatocellular carcinoma in HCV-infected alcoholic patients with cirrhosis.
Plasma protein biomarkers of hepatocellular carcinoma in HCV-infected alcoholic patients with cirrhosis.
复制标题
DOI：
10.1371/journal.pone.0118527
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
de la Mata M
中科院分区：
文献类型：
--
作者：
Ferrín G;Rodríguez-Perálvarez M;Aguilar-Melero P;Ranchal I;Llamoza C;Linares CI;González-Rubio S;Muntané J;Briceño J;López-Cillero P;Montero-Álvarez JL;de la Mata M
肝细胞癌（HCC）是世界上最常见和最致命的癌症之一，除非及时诊断，否则治疗选择有限。慢性丙型肝炎病毒（HCV）感染和持续大量饮酒是HCC发展的独立危险因素，这可能会诱导不同于单独引起的特异性蛋白表达模式。该研究的目的是确定蛋白质生物标志物，用于检测HCV感染的酒精性肝硬化患者的HCC，以提高生存率。我们使用2-D DIGE结合MALDI-TOF/TOF质谱法，比较了52例HCV感染的酒精性肝癌患者和非肝癌患者血浆样本的蛋白质表达谱。用Decyder软件对二维DIGE结果进行统计学分析，并用Western-blot和ELISA进行验证。在HCV感染的酒精患者的血浆样本中，我们发现羧肽酶-N、血浆铜蓝蛋白（CP）、补体成分4a（C4 a）、纤维蛋白原-α（FGA）、免疫球蛋白μ链C区、血清白蛋白和血清对氧磷酶/芳基酯酶1（PON 1）的表达谱存在显著差异。所鉴定蛋白质的血浆/血清水平的失调与HCV、乙醇消耗和/或HCC进展相关。在通过ELISA进行的验证中，HCC患者中C4 a血清浓度增加（2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029），是多变量分析中HCC的唯一独立预测因子（OR = 2.15; p = 0.015），AUROC = 0.70。C4 a、FGA、CP和PON 1的组合略微改善了单独C4 a的预测能力（AUROC 0.81）。总之，我们鉴定了与急性期反应、氧化应激或免疫反应相关的蛋白质，其在血浆中的差异表达可能归因于HCC的存在。其中，C4 a及其与CP、FGA和PON 1的组合可以被认为是检测HCV感染的酒精患者中的HCC的潜在可靠的生物标志物。
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers in the world, with limited options for treatment unless timely diagnosed. Chronic hepatitis C virus (HCV) infection and persistent heavy alcohol consumption are independent risk factors for HCC development, which may induce a specific protein expression pattern different from those caused separately. The aim of the study was to identify protein biomarkers for the detection of HCC in HCV-infected alcoholic patients with cirrhosis in order to improve survival. We compared protein expression profiles of plasma samples from 52 HCV-infected alcoholic patients with and without HCC, using 2-D DIGE coupled with MALDI-TOF/TOF mass spectrometry. The 2-D DIGE results were analyzed statistically using Decyder software, and verified by western-blot and ELISA. In plasma samples from HCV-infected alcoholic patients, we found significantly differential expression profiles of carboxypeptidase-N, ceruloplasmin (CP), complement component 4a (C4a), fibrinogen-alpha (FGA), immunoglobulin mu chain C region, serum albumin, and serum paraoxonase/arylesterase 1 (PON1). Deregulation of plasma/serum levels of the identified proteins was associated to HCV, ethanol consumption, and/or HCC progression. In the validation through ELISA, C4a serum concentration was increased in HCC patients (2.4±1 ng/mg vs 1.8±0.6 ng/mg; p = 0.029), being the only independent predictor of HCC in the multivariate analysis (OR = 2.15; p = 0.015), with an AUROC = 0.70. The combination of C4a, FGA, CP and PON1 improved slightly the predictive ability of C4a alone (AUROC 0.81). In conclusion, we identified proteins related to acute-phase response, oxidative stress, or immune response, whose differential expression in plasma may be attributed to the presence of HCC. Among them, C4a, and its combination with CP, FGA and PON1, could be considered as potentially reliable biomarkers for the detection of HCC in HCV-infected alcoholic patients.
登录
查看更多内容
影响因子：
3.4
作者：
Feng, JT;Liu, YK;Tang, ZY
通讯作者：
Tang, ZY
影响因子：
3.7
作者：
Fye HK;Wright-Drakesmith C;Kramer HB;Camey S;Nogueira da Costa A;Jeng A;Bah A;Kirk GD;Sharif MI;Ladep NG;Okeke E;Hainaut P;Taylor-Robinson SD;Kessler BM;Mendy ME
通讯作者：
Mendy ME
影响因子：
2.9
作者：
ENTWISTLE, RA;FURCHT, LT
通讯作者：
FURCHT, LT
影响因子：
5.4
作者：
Banerjee, Arup;Mazumdar, Budhaditya;Ray, Ranjit
通讯作者：
Ray, Ranjit
影响因子：
5
作者：
ERDOS, EG;WOHLER, IM;WESTERMAN, MP
通讯作者：
WESTERMAN, MP