Identification of HGD and GSTZ1 as Biomarkers Involved Metabolic Reprogramming in Kidney Renal Clear Cell Carcinoma.
Identification of HGD and GSTZ1 as Biomarkers Involved Metabolic Reprogramming in Kidney Renal Clear Cell Carcinoma.
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鉴定 HGD 和 GSTZ1 作为肾透明细胞癌代谢重编程生物标志物
DOI：
10.3390/ijms23094583
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发表时间：
2022-04-21
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肾透明细胞癌(KIRC)是肾细胞癌的主要组织学亚型，占患者的80%以上，预后差。由于早期无症状，大多数患者被诊断为晚期。晚期KIRC由于其对放疗和化疗的固有抵抗力，其预后极差。因此，迫切需要全面了解KIRC的分子机制，开发有效的早期诊断和治疗策略。在这项研究中，我们的目标是识别与预后相关的生物标志物，并分析其与肿瘤进展的关系。代谢变化是肾癌的一个重要特征，富马酸的减少使我们能够靶向酪氨酸代谢途径。以肿瘤基因组图谱为基础，通过生物信息学分析鉴定了与KIRC预后相关的同源1，2-双加氧酶和谷胱甘肽S转移酶Zeta1。从机制上讲，我们发现HGD和GSTZ1的减少促进了KIRC的有氧糖酵解，协调了肿瘤细胞内氨基酸代谢和能量代谢的平衡，最终激活了肿瘤细胞周期和肿瘤进展。综上所述，我们确定酪氨酸代谢酶HGD和GSTZ1为KIRC的生物标志物，这将加深对肿瘤代谢谱的了解，为KIRC的诊断和治疗提供新的策略和理论支持，并为未来的临床研究提供参考。
Kidney renal clear cell carcinoma (KIRC) with poor prognosis is the main histological subtype of renal cell carcinoma, accounting for more than 80% of patients. Most patients are diagnosed at an advanced stage due to being asymptomatic early on. Advanced KIRC has an extremely poor prognosis due to its inherent resistance to radiotherapy and chemotherapy. Therefore, a comprehensive understanding of the molecular mechanisms of KIRC and the development of effective early diagnostic and therapeutic strategies is urgently needed. In this study, we aimed to identify the prognosis-related biomarker and analyzed its relationship with tumor progression. Metabolic changes are an important feature of kidney cancer, where the reduction of fumarate allows us to target the tyrosine metabolic pathway. The homogentisate 1,2-dioxygenase (HGD) and glutathione S-transferase zeta 1 (GSTZ1) related with prognosis of KIRC was identified through bioinformatics analysis based on The Cancer Genome Atlas (TCGA) databases. Mechanistically, we found that decreased HGD and GSTZ1 promote aerobic glycolysis in KIRC, coordinate the balance of amino acid metabolism and energy metabolism in tumor cells, and ultimately activate the tumor cell cycle and tumor progression. In summary, we identified the tyrosine metabolizing enzymes HGD and GSTZ1 as biomarkers of KIRC, which will further the understanding of the tumor metabolism profile, provide novel strategies and theoretical support for diagnosing and treating KIRC and as referential for future clinical research.
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