Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer
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, ha...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1002186/full |
| _version_ | 1811175331422273536 |
|---|---|
| author | Huihui Li Li Wang Wei Zhang Youting Dong Yefeng Cai Yefeng Cai Xiaoli Huang Xiaoli Huang Xubin Dong |
| author_facet | Huihui Li Li Wang Wei Zhang Youting Dong Yefeng Cai Yefeng Cai Xiaoli Huang Xiaoli Huang Xubin Dong |
| author_sort | Huihui Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T19:35:23Z |
| format | Article |
| id | doaj.art-3f93f922093045288f0342e2ad4660c4 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T19:35:23Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3f93f922093045288f0342e2ad4660c42023-01-30T07:28:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-01-011210.3389/fonc.2022.10021861002186Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancerHuihui Li0Li Wang1Wei Zhang2Youting Dong3Yefeng Cai4Yefeng Cai5Xiaoli Huang6Xiaoli Huang7Xubin Dong8Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastroenterology, Wenzhou Central Hospital, Wenzhou, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaShanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaBreast 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.1002186/fullPKMYT1prognosismulti-omicsTNBC subtypesimmune infiltration |
| spellingShingle | Huihui Li Li Wang Wei Zhang Youting Dong Yefeng Cai Yefeng Cai Xiaoli Huang Xiaoli Huang Xubin Dong Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer Frontiers in Oncology PKMYT1 prognosis multi-omics TNBC subtypes immune infiltration |
| title | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
| title_full | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
| title_fullStr | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
| title_full_unstemmed | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
| title_short | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
| title_sort | overexpression of pkmyt1 associated with poor prognosis and immune infiltration may serve as a target in triple negative breast cancer |
| topic | PKMYT1 prognosis multi-omics TNBC subtypes immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1002186/full |
| work_keys_str_mv | AT huihuili overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT liwang overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT weizhang overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT youtingdong overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT yefengcai overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT yefengcai overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT xiaolihuang overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT xiaolihuang overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT xubindong overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer |