High expression of PALB2 predicts poor prognosis in patients with advanced breast cancer

Li, Jingquan; Li, Mian; Chen, Peizhan; Ba, Qian

doi:10.1002/2211-5463.12356

Cited by 18 publications

(12 citation statements)

References 19 publications

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“…PALB2 acts as a tumor suppressor protein by mediating DNA repair and thereby suppressing genome instability [51]. In addition, its overexpression in tissue has recently been linked to a worse outcome in patients with MBC [52]. We found similar results on CTCs concerning patients' outcomes and found higher expression after one cycle of therapy, which might be induced to promote DNA repair.…”

Section: Discussionsupporting

confidence: 69%

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Pereira-Veiga¹,

Martínez‐Fernández

Abuín³

et al. 2019

Cancers

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The study of circulating tumor cells (CTCs) has a huge clinical interest in advance and metastatic breast cancer patients. However, many approaches are biased by the use of epithelial markers, which underestimate non-epithelial CTCs phenotypes. CTCs enumeration provides valuable prognostic information; however, molecular characterization could be the best option to monitor patients throughout the disease since it may provide more relevant clinical information to the physicians. In this work, we aimed at enumerating and performing a molecular characterization of CTCs from a cohort of 20 patients with metastatic breast cancer (MBC), monitoring the disease at different time points of the therapy, and at progression when it occurred. To this end, we used a CTC negative enrichment protocol that allowed us to recover a higher variety of CTCs phenotypes. With this strategy, we were able to obtain gene expression data from CTCs from all the patients. In addition, we found that high expression levels of PALB2 and MYC were associated with a worse outcome. Interestingly, we identified that CTCs with an EpCAMhighVIMlowALDH1A1high signature showed both shorter overall survival (OS) and progression-free survival (PFS), suggesting that CTCs with epithelial-stem features had the most aggressive phenotype.

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Section: Discussionsupporting

confidence: 69%

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Pereira-Veiga¹,

Martínez‐Fernández

Abuín³

et al. 2019

Cancers

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“…As EMT was the most prominent signaling pathway associated with decreased OS, the expression levels of certain EMT genes in PDAC cells were assessed. Consistent with the GSEA results, PALB2-knockdown affected the expression levels of Slug, Zeb1 and vimentin, which was also consistent with a previous study ( 29 ). However, the extent to which the other significantly associated signaling pathways contribute to the decreased OS of patients with high PALB2 expression requires further investigation.…”

Section: Discussionsupporting

confidence: 92%

“…Upregulated BRCA2 expression predicts a poor prognosis in patients with breast carcinoma ( 28 ). Similarly, elevated PALB2 expression is associated with poor clinical outcomes in patients with advanced breast carcinoma ( 29 ). However, independent research has indicated no association between PALB2 expression and breast cancer prognosis ( 30 ), and therefore additional studies are required to clarify this interaction.…”

Section: Discussionmentioning

confidence: 99%

PALB2 upregulation is associated with a poor prognosis in pancreatic ductal adenocarcinoma

Huang

Wang

et al. 2021

Oncol Lett

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During DNA repair, BRCA1 and BRCA2 interact with the tumor suppressor partner and localizer of BRCA2 (PALB2). PALB2 mutations are associated with an increased risk of breast and ovarian carcinoma, and upregulated PALB2 expression is associated with poor clinical outcomes. The present study investigated the role and prognostic value of PALB2 in pancreatic ductal adenocarcinoma (PDAC). PALB2 expression was inhibited using a small interfering RNA in PDAC cell lines, and the subsequent effects on cell proliferation and migration were investigated. Tissue microarrays from 157 patients undergoing a pancreaticoduodenectomy for PDAC were analyzed via immunohistochemistry, and PALB2 expression was compared with patient outcomes using Kaplan-Meier curves and the multivariate Cox regression model. PALB2-knockdown in PDAC cells had little effect on cell proliferation, but significantly decreased cell migration. Relatively high PALB2 expression was observed in PDAC tissues compared with in peritumoral tissues. Overall survival (OS) was negatively associated with PALB2 expression. TNM stage and PALB2 expression were identified as independent prognostic factors associated with OS via multivariate analysis. Overall, the present study demonstrated that PDAC cell migration was dependent on PALB2, which was further supported by the finding that elevated PALB2 expression in PDAC tissues was associated with poor survival in patients with PDAC. Therefore, PALB2 may serve as a novel prognostic marker in PDAC, which may aid with the development of therapeutic strategies for the disease.

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“…Literature study shows that the following proteins are in close association with BC, like FGFR2 [20], CTLA4 [10], MREII [18], BRAD1 [15], PALB2 [22], p53R2 [23], CDK 8 [6], CDK 4/6 [32], AKT1 [35], BRD4 [42], MDM2 [12], BRCA 1 and 2 [9], and RAD51 [24]. The 3D structure proteins and their respective protein data bank (PDB) Ids are given in Table 1.…”

Section: Selection Of Proteins For Dockingmentioning

confidence: 99%

In silico molecular docking studies and MM/GBSA analysis of coumarin-carbonodithioate hybrid derivatives divulge the anticancer potential against breast cancer

Pattar

Adhoni

Kamanavalli

et al. 2020

Beni-Suef Univ J Basic Appl Sci

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Background: There are many biomarkers associated with breast cancer. Higher expression of PIK3CA (Phosphoinositide 3-kinase Cα), in its upregulated form, is associated with Hr + and Her2 − breast cancer; therefore, many drugs were synthesized against this protein to treat breast cancer patients. FDA recently approved that the drug alpelisib also inhibits PI3KCα (PDB ID-5DXT) in BC patients with Hr + and Her2 −. In present study, we have exploited fourteen coumarin-carbonodithioate derivatives and alpelisib against this protein along with eighteen others which are responsible for causing BC through computational analysis. We have used Schrödinger Maestro 11.2 version for our in silico docking study, and to calculate relative binding energies of ligands, we used prime MM-GBSA module. Result: Docking study revealed that among all fourteen compounds, 2f, 2a, 2d, and 2e showed the highest G score than the alpelisib and coumarin against PI3KCα with − 9.3, − 9.0, − 9.0 and − 9.1 kcal/mol respectively, along with individual G score of alpelisib (− 8.9) and coumarin (− 7.9). Prime MM-GBSA analysis gave the relative binding energies of alpelisib, 2f, and 2e with − 19.94864535, − 18.63076296 and − 13.07341286 kcal/mol sequentially. Conclusion: This study provides an insight into the coumarin-carbonodithioate derivatives that could act as inhibitors of PI3KCα like alpelisib. Further prime MM-GBSA study revealed ligand binding energies and ligands strain energies.

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High expression of PALB2 predicts poor prognosis in patients with advanced breast cancer

Cited by 18 publications

References 19 publications

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

PALB2 upregulation is associated with a poor prognosis in pancreatic ductal adenocarcinoma

In silico molecular docking studies and MM/GBSA analysis of coumarin-carbonodithioate hybrid derivatives divulge the anticancer potential against breast cancer

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