Systematic expression analysis of WEE family kinases reveals the importance of PKMYT1 in breast carcinogenesis
Systematic expression analysis of WEE family kinases reveals the importance of PKMYT1 in breast carcinogenesis
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WEE 家族激酶的系统表达分析揭示了 PKMYT1 在乳腺癌发生中的重要性。
DOI：
10.1111/cpr.12741
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发表时间：
2019-12-14
影响因子：
8.5
通讯作者：
Yang, Wulin
中科院分区：
文献类型：
--
作者：
Liu, Yu;Qi, Jian;Yang, Wulin
目的许多癌细胞依赖于由WEE家族激酶调控的G2检查点机制来维持基因组完整性。PKMYT1基因，作为WEE家族激酶的一员，参与G2检查点监视并可能与肿瘤发生有关，但其在乳腺癌中的作用仍不清楚。材料与方法在本研究中，我们采用一套生物信息学工具，联合分析WEE家族激酶的表达，探讨PKMYT1在乳腺癌中的预后价值。结果PKMYT1是乳腺癌中唯一经常过表达的WEE家族激酶成员。KM绘图数据表明，PKMYT1异常高表达预示着不良预后，特别是对于一些亚型，如luminal A/B和三阴性（TNBC）型。此外，PKMYT1的上调与HER2阳性（HER2+）、基底样（basal-like）、TNBC状态和Scarff， Bloom和Richardson （SBR）分类增加有关。共表达分析显示，PKMYT1与polo样激酶1 （PLK1）有很强的正相关，这意味着它们可能通过同步快速的细胞周期和高质量的基因组维持来协同调节癌细胞增殖。总之，本研究表明PKMYT1在乳腺癌中经常发现过表达，并预示着不良预后，这意味着它是一种有吸引力的乳腺癌治疗靶点。
Objectives Many cancer cells depend on G2 checkpoint mechanism regulated by WEE family kinases to maintain genomic integrity. The PKMYT1 gene, as a member of WEE family kinases, participates in G2 checkpoint surveillance and probably links with tumorigenesis, but its role in breast cancer remains largely unclear. Materials and Methods In this study, we used a set of bioinformatic tools to jointly analyse the expression of WEE family kinases and investigate the prognostic value of PKMYT1 in breast cancer. Results The results indicated that PKMYT1 is the only frequently overexpressed member of WEE family kinases in breast cancer. KM plotter data suggests that abnormally high expression of PKMYT1 predicts poor prognosis, especially for some subtypes, such as luminal A/B and triple-negative (TNBC) types. Moreover, the up-regulation of PKMYT1 was associated with HER2-positive (HER2+), basal-like (Basal-like), TNBC statuses and increased classifications of Scarff, Bloom and Richardson (SBR). Co-expression analysis showed PKMYT1 has a strong positive correlation with Polo-like kinase 1 (PLK1), implying they may cooperate in regulating cancer cell proliferation by synchronizing rapid cell cycle with high quality of genome maintenance. Conclusions Collectively, this study demonstrates that overexpression of PKMYT1 is always found in breast cancer and predicts unfavourable prognosis, implicating it as an appealing therapeutic target for breast carcinoma.