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High expression levels of pyrimidine metabolic rate-limiting enzymes are adverse prognostic factors in lung adenocarcinoma: a study based on The Cancer Genome Atlas and Gene Expression Omnibus datasets.
Purinergic Signalling ( IF 3.5 ) Pub Date : 2020-07-08 , DOI: 10.1007/s11302-020-09711-4
Haiwei Wang 1, 2 , Xinrui Wang 1, 2 , Liangpu Xu 1, 2 , Ji Zhang 3 , Hua Cao 1, 2
Affiliation  

Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.



中文翻译:

嘧啶代谢限速酶的高表达水平是肺腺癌的不良预后因素:一项基于癌症基因组图谱和基因表达综合数据集的研究。

代谢重编程在许多类型的癌症中都有描述,并且与临床结果相关。然而,嘧啶代谢信号通路在肺腺癌(LUAD)中的预后意义尚不清楚。使用基因表达综合 (GEO) 和癌症基因组图谱 (TCGA) 数据集,我们发现嘧啶代谢信号通路在 LUAD 中显着富集。与正常肺组织相比,嘧啶代谢率限制酶在肺肿瘤组织中高表达。嘧啶代谢速率限制酶的高表达水平与不良预后相关。然而,嘌呤能受体 P2RX1、P2RX7、P2RY12、P2RY13 和 P2RY14 在肺癌组织中相对下调,并与良好的预后相关。而且,我们发现低 DNA 甲基化、DNA 扩增和 TP53 突变有助于肺癌细胞中嘧啶代谢速率限制酶的高表达水平。此外,联合嘧啶代谢限速酶对 LUAD 具有显着的预后影响。综上所述,嘧啶代谢限速酶在膀胱癌、乳腺癌、结肠癌、肝癌和胃癌中高表达。嘧啶代谢率限制酶的高表达水平与肝癌的不良预后相关。总体而言,我们的结果表明嘧啶代谢率限制酶 CAD、DTYMK、RRM1、RRM2、TK1、TYMS、UCK2、NR5C2 和 TK2 的 mRNA 水平可预测肺癌以及其他癌症。和 TP53 突变有助于肺癌细胞中嘧啶代谢率限制酶的高表达水平。此外,联合嘧啶代谢限速酶对 LUAD 具有显着的预后影响。综上所述,嘧啶代谢限速酶在膀胱癌、乳腺癌、结肠癌、肝癌和胃癌中高表达。嘧啶代谢率限制酶的高表达水平与肝癌的不良预后相关。总体而言,我们的结果表明嘧啶代谢率限制酶 CAD、DTYMK、RRM1、RRM2、TK1、TYMS、UCK2、NR5C2 和 TK2 的 mRNA 水平可预测肺癌以及其他癌症。和 TP53 突变导致肺癌细胞中嘧啶代谢率限制酶的高表达水平。此外,联合嘧啶代谢限速酶对 LUAD 具有显着的预后影响。综上所述,嘧啶代谢限速酶在膀胱癌、乳腺癌、结肠癌、肝癌和胃癌中高表达。嘧啶代谢率限制酶的高表达水平与肝癌的不良预后相关。总体而言,我们的结果表明嘧啶代谢率限制酶 CAD、DTYMK、RRM1、RRM2、TK1、TYMS、UCK2、NR5C2 和 TK2 的 mRNA 水平可预测肺癌以及其他癌症。

更新日期:2020-07-08
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