Department of Computational Biomedicine, Vingroup Big Data Institute, Hanoi, Vietnam.
Department of Computer Vision, Vingroup Big Data Institute, Hanoi, Vietnam.
PLoS One. 2020 Jun 15;15(6):e0229276. doi: 10.1371/journal.pone.0229276. eCollection 2020.
Tyrosine is mainly degraded in the liver by a series of enzymatic reactions. Abnormal expression of the tyrosine catabolic enzyme tyrosine aminotransferase (TAT) has been reported in patients with hepatocellular carcinoma (HCC). Despite this, aberration in tyrosine metabolism has not been investigated in cancer development. In this work, we conduct comprehensive cross-platform study to obtain foundation for discoveries of potential therapeutics and preventative biomarkers of HCC. We explore data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Kaplan Meier plotter (KM plotter) and performed integrated analyses to evaluate the clinical significance and prognostic values of the tyrosine catabolic genes in HCC. We find that five tyrosine catabolic enzymes are downregulated in HCC compared to normal liver at mRNA and protein level. Moreover, low expression of these enzymes correlates with poorer survival in patients with HCC. Notably, we identify pathways and upstream regulators that might involve in tyrosine catabolic reprogramming and further drive HCC development. In total, our results underscore tyrosine metabolism alteration in HCC and lay foundation for incorporating these pathway components in therapeutics and preventative strategies.
酪氨酸主要在肝脏中通过一系列酶促反应降解。已有报道称，肝癌（HCC）患者的酪氨酸分解酶酪氨酸氨基转移酶（TAT）表达异常。尽管如此，酪氨酸代谢的异常在癌症发展中尚未得到研究。在这项工作中，我们进行了全面的跨平台研究，为 HCC 的潜在治疗和预防生物标志物的发现提供了基础。我们探索了来自癌症基因组图谱（TCGA）、基因表达综合组（GEO）、基因表达谱交互分析（GEPIA）、Oncomine 和 Kaplan Meier plotter（KM plotter）的数据，并进行了综合分析，以评估酪氨酸分解基因在 HCC 中的临床意义和预后价值。我们发现与正常肝脏相比，HCC 中五种酪氨酸分解酶在 mRNA 和蛋白质水平上均下调。此外，这些酶的低表达与 HCC 患者的生存预后较差相关。值得注意的是，我们确定了可能涉及酪氨酸分解重编程并进一步驱动 HCC 发展的途径和上游调节剂。总的来说，我们的研究结果强调了 HCC 中酪氨酸代谢的改变，并为将这些途径成分纳入治疗和预防策略奠定了基础。
