Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer

Huihui Li; Li Wang; Wei Zhang; Youting Dong; Yefeng Cai; Xiaoli Huang; Xubin Dong

doi:10.3389/fonc.2022.1002186

Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer

Front Oncol. 2023 Jan 30:12:1002186. doi: 10.3389/fonc.2022.1002186. eCollection 2022.

Authors

Huihui Li¹, Li Wang², Wei Zhang¹, Youting Dong³, Yefeng Cai^{1

4}, Xiaoli Huang^{1

4}, Xubin Dong¹

Affiliations

¹ Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Gastroenterology, Wenzhou Central Hospital, Wenzhou, China.
³ Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Breast cancer (BC) is one of the most common malignancies among women worldwide. It is necessary to search for improvement in diagnosis and treatment methods to improve the prognosis. Protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, has been studied in some tumors except BC. This study has explored that PKMYT1 functional role by bioinformatics methods combined with local clinical samples and experiments. Comprehensive analysis showed that PKMYT1 expression was higher in BC tissues, especially in advanced patients than that in normal breast tissues. The expression of PKMYT1 was an independent determinant for BC patients' prognosis when combined with the clinical features. In addition, based on multi-omics analysis, we found that the PKMYT1 expression was closely relevant to several oncogenic or tumor suppressor gene variants. The analysis of single-cell sequencing indicated that PKMYT1 expression was upregulated in triple-negative breast cancer (TNBC), consistent with the results of bulk RNA-sequencing. High PKMYT1 expression was correlated with a poor prognosis. Functional enrichment analysis revealed that PKMYT1 expression was associated with cell cycle-related, DNA replication-related, and cancer-related pathways. Further research revealed that PKMYT1 expression was linked to immune cell infiltration in the tumor microenvironment. Additionally, loss-of-function experiments in vitro were performed to investigate the role of PKMYT1. TNBC cell lines' proliferation, migration, and invasion were inhibited when PKMYT1 expression was knock-down. Besides, the down-regulation of PKMYT1 induced apoptosis in vitro. As a result, PKMYT1 might be a biomarker for prognosis and a therapeutic target for TNBC.

Keywords: PKMYT1; TNBC subtypes; immune infiltration; multi-omics; prognosis.

Grants and funding

This study was supported by The Natural Science Foundation of Zhejiang Province (No. Q23H160067), Wenzhou Science and Technology Plan Project (Y20220180 and Y20190388), and Scientific Research Incubator Project of The First Affiliated Hospital of Wenzhou Medical University (FHY2019003).