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.
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.
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DOI：
10.1007/s11302-020-09711-4
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发表时间：
2020-09
影响因子：
3.5
通讯作者：
Cao H
中科院分区：
文献类型：
--
作者：
Wang H;Wang X;Xu L;Zhang J;Cao H
许多类型的癌症都描述了代谢重编程，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，嘧啶代谢限速酶在肺肿瘤组织中高表达。嘧啶代谢限速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，并且与良好的预后相关。此外，我们发现DNA低甲基化、DNA扩增和TP53突变导致肺癌细胞中嘧啶代谢限速酶的高表达水平。此外，联合嘧啶代谢限速酶对 LUAD 具有显着的预后作用。综合来看，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。嘧啶代谢限速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限速酶 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。本文的在线版本 (10.1007/s11302-020-09711-4) 包含补充材料，可供授权用户使用。
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. The online version of this article (10.1007/s11302-020-09711-4) contains supplementary material, which is available to authorized users.
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
3.5
作者：
Burnstock G;Knight GE
通讯作者：
Knight GE
影响因子：
51.1
作者：
Miller, Vincent A.;Hirsh, Vera;Yang, James Chih-Hsin
通讯作者：
Yang, James Chih-Hsin
影响因子：
8
作者：
Chitale, D.;Gong, Y.;Taylor, B. S.;Broderick, S.;Brennan, C.;Somwar, R.;Golas, B.;Wang, L.;Motoi, N.;Szoke, J.;Reinersman, J. M.;Major, J.;Sander, C.;Seshan, V. E.;Zakowski, M. F.;Rusch, V.;Pao, W.;Gerald, W.;Ladanyi, M.
通讯作者：
Ladanyi, M.
影响因子：
7.2
作者：
Gottlieb, Eyal;Vousden, Karen H.
通讯作者：
Vousden, Karen H.