Clinical impact of serum transforming growth factor-alpha mRNA as a predictive biomarker for the prognosis of fulminant hepatitis

Clinical impact of serum transforming growth factor-alpha mRNA as a predictive biomarker for the prognosis of fulminant hepatitis
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DOI:
10.1007/s12072-008-9053-6
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发表时间:
2008-06-01
影响因子:
6.6
通讯作者:
Shiota, Goshi
Shiota, Goshi
中科院分区:
医学2区
文献类型:
--
作者:
Miura, Norimasa;Kabashima, Hiroko;Shiota, Goshi

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目的 我们之前报道过,使用定量、一步、实时 RT-PCR 测量血清端粒酶逆转录酶 (hTERT) mRNA 优于肝细胞癌和肺癌的传统肿瘤标志物。在这里,我们检查了血清再生相关mRNA检测作为暴发性肝炎(FH)的生物标志物。方法在53名患者中,包括17名急性肝炎(AH)、7名重型肝炎(SH)、4名迟发性肝衰竭(LOHF)和25名FH患者,我们测量了hTERT、肝细胞生长因子(HGF)、肝细胞生长因子受体(c-met)、表皮生长因子受体的血清mRNA水平EGFR)和转化生长因子-α(TGF-α)。我们检查了该技术在 FH 诊断中的敏感性和特异性,以及与其他临床和预后测试相比的临床和预后意义。结果 FH 入院时血清 TGF-α mRNA 拷贝数显着低于 AH 和 SH。在 FH 中,幸存者的 TGF-α mRNA 水平比死亡或接受肝移植的患者高 10(6) 倍 (P = 0.034),尽管这些患者没有受到其他临床参数的歧视。 TGF-α mRNA 对 FH 预后的敏感性/特异性为 74.3/65.5%。在四种预后评分系统中,只有 logit-lambda 可用于预后评估。结论 TGF-α mRNA 是 FH 结果的早期预测因子,也是肝脏再生能力较低的敏感生物标志物。该测定可以帮助促进早期治疗选择,例如肝移植。
Purpose We previously reported that measuring serum telomerase reverse transcriptase (hTERT) mRNA with a quantitative, one-step, real-time RT-PCR was superior to conventional tumor markers for hepatocellular carcinoma and lung cancer. Here, we examined serum regenerationrelated mRNA detection as a biomarker for fulminant hepatitis (FH).Methods In 53 patients, including 17 patients with acute hepatitis (AH), seven with severe hepatitis (SH), four with late-onset hepatic failure (LOHF), and 25 with FH, we measured serum mRNA levels of hTERT, hepatocyte growth factor (HGF), hepatocyte growth factor receptor (c-met), epidermal growth factor receptor EGFR), and transforming growth factor-alpha (TGF-alpha). We examined the sensitivity and specificity of the technique in FH diagnosis as well as its clinical and prognostic significance compared with other clinical and prognostic tests.Results Serum copy number of TGF-alpha mRNA in FH on admission was significantly smaller than in AH and SH. In FH, TGF-alpha mRNA level was 10(6)-fold higher in survivors than in patients who died or received liver transplants (P = 0.034), although these patients were not discriminated by other clinical parameters. The sensitivity/specificity for prognosis in FH was 74.3/65.5% for TGF-alpha mRNA. Of four prognostic scoring systems, only logit-lambda was useful for prognosis assessment.Conclusions TGF-alpha mRNA is an early predictor of FH outcome and a sensitive biomarker of lower regenerative liver capacity. This assay could help facilitate early therapy choice, such as liver transplantation.