Abstract
ObjectivesMany 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 MethodsIn 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.ResultsThe 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.ConclusionsCollectively, 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.
Highlights
Malignant tumours are the most threatening human diseases around the world
Using the Kaplan-Meier (KM) plotter as an indicator of prognostic value of PKMYT1 expression, we found that increased expression of PKMYT1 mRNA was significantly associated with overall survival (OS), post-progression survival (PPS), relapse-free survival (RFS) and distant metastatic-free survival (DMFS) (Figure 3D-G)
Diagnosis and treatment of breast cancer remains an area of active investigation.[43]
Summary
Malignant tumours are the most threatening human diseases around the world. In 2018, there were about 18.1 million new cancer cases and 9.6 million cancer-related deaths.[1]. Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death among women The incidence of this aggressive disease remains alarmingly high with more than one million newly diagnosed cases each year.[1-3]. Because of the loss-of-function of tumour suppressor genes, such as mutations in p53 that leads to the inactivation of the G1 checkpoint, many cancerous cells heavily rely on G2/M checkpoint to ensure its genomic stability and survival advantage. Study has shown that WEE1 inhibitors are effective against TP53-mutant cancer cells, which account for over 80% of triple-negative breast cancer (TNBC) cases.[9]. TA B L E 1 PKMYT1 expressions are upregulated in different subtypes of breast carcinoma inhibitor renders apoptosis in TNBC cells, but its clinical application remains limited.[9,14,15]. We applied a wide range of integrated bioinformatics approach to assess the importance of PKMYT1 by analysing the expression, potential function and prognostic impact of PKMYT1 in human breast cancer
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