Significance of BRCA1 expression in breast and ovarian cancer patients with brain metastasis – A multicentre study

Szarszewska, Monika; Markowska, Anna; Jach, Robert; Marszałek, Andrzej; Filas, Violetta; Bednarek, Wiesława; Olejek, Anita; Tomczak, Piotr; Sajdak, Stefan; Nowak‐Markwitz, Ewa; Jaszczyńska-Nowinka, Karolina; Stanisławiak-Rudowicz, Joanna; Gryboś, Anna; Chudecka‐Głaz, Anita; Gryboś, Marian; Adamska, Krystyna; Markowska, Janina; Knapp, Paweł

doi:10.1016/j.advms.2018.12.007

Cited by 10 publications

(10 citation statements)

References 29 publications

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“…Breast cancer cells expressing the epidermal growth factor receptor oncogene possess neurotropic properties, and commonly metastasize to the central nervous system (12). A recent study demonstrated a significant correlation between the low expression level of breast cancer type 1 susceptibility protein in the tumor tissues of patients with breast cancer and brain metastasis, but the specific mechanism remains to be fully elucidated (13). In a previous study, investigation of circular RNA (circRNA) expression by high-throughput sequencing identified numerous circRNAs as potential molecular markers for brain metastasis in breast cancer (14).…”

Section: Introductionmentioning

confidence: 99%

Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

Xiong

Chen

2019

Int J Mol Med

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To verify whether amyloid precursor protein (APP) affects the migration and invasion of breast cancer cell lines, and to understand its underlying mechanisms, epithelial-mesenchymal transition (EMT), the mitogen-activated protein kinase (MAPK) signaling pathway and the matrix metalloproteinase (MMP) family were investigated in MDA-MB-231, MCF-7 and BT474 human breast cancer cells. Breast cancer cell lines were transfected with plasmids containing APP coding sequences (pEGFP-n1-APP) and APP short hairpin RNA (pENTR APP shRNA). APP overexpres-sion efficiency, knockout efficiency and the expression levels of related genes were tested using reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses. The effects of APP and mitogen-activated protein kinase kinase (MEK) inhibitor on cell migration and invasion were examined using Transwell assays. The results demonstrated that APP was significantly upregulated in the pEGFP-n1-APP group (P<0.05), and significantly downregulated in the pENTR APP shRNA group (P<0.05), compared with the control group. APP overexpression increased the migratory and invasive ability of human breast cancer cells (P<0.05), whereas APP silencing significantly inhibited cell migration and invasion (P<0.05). RT-qPCR and western blot analysis results suggested that APP overexpression significantly increased the expression of MMP-9, MMP-2, MMP-3, N-cadherin and vimentin (P<0.05). In addition, the enhanced expression of APP markedly affected the phosphorylation of mitogen-activated protein kinase kinase kinase 11 (MLK3), mitogen-activated protein kinase kinase 4 (MEK4) and mitogen-activated protein kinase 10 (JNK3; P<0.05). Additionally, APP overexpression had no effect on the total expression levels of MLK3, MEK4, and JNK3; however, APP overexpression significantly decreased the expression levels of E-cadherin and cytokeratin (P<0.05). Conversely, APP silencing had the opposite effects. When cells were treated with the MEK inhibitor PD0325901, the expression of APP was not altered, nor was the expression levels of MEK and its upstream signaling molecules. Taken together, the present findings suggested that APP could affect the migration and invasion of human breast cancer cells by mediating the activation of the MAPK signaling pathway, thereby promoting the EMT process.

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Section: Introductionmentioning

confidence: 99%

Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

Xiong

Chen

2019

Int J Mol Med

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“…In the literature, studies are investigating the relationship between BRCA mutation status and brain metastasis in patients with ovarian cancer [10,15,26]. The BRCA mutation was found to be more frequent in patients with ovarian cancer with brain metastasis [15,16]. In a recent study, Stasenko et al [10] remarked that patients with BRCA mutations had longer survival times compared with patients with wild-type BRCA.…”

Section: Discussionmentioning

confidence: 99%

“…The number of metastatic lesions and treatment modalities are the leading independent prognostic factors [7,14]. The BRCA mutation and androgen receptor status of the primary tumor are new emerging prognostic factors [10,13,15,16].…”

Section: Introductionmentioning

confidence: 99%

The clinical outcomes of ovarian cancer in patients with brain metastasis

2021

EJGO

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To present the clinical characteristics and treatment outcomes of patients with ovarian cancer with brain metastasis. Methods: This study was designed as a retrospective observational study. Patients' data were obtained from hospital records. Patients who were diagnosed with brain metastatic ovarian cancer in two tertiary referral centers between 2012 and 2020 were included in the study. Results: In total, there were 56 patients diagnosed as having brain metastatic ovarian cancer. The median age was 56 years, 91% of patients were at an advanced stage at initial diagnosis. The median time from the initial diagnosis to brain metastasis was 34.0 months. Sixty-seven percent of patients were determined as having multiple brain metastatic lesions. Whole brain radiotherapy (WBRT) , stereotactic radiosurgery (SRS) and combined approach were utilized as primary treatment. The 1 and 2-year survival rates were 38% and 17%, respectively. Patient age and tumor histology were found to be significant prognostic factors that impact the survival in univariate analyses. The 1-year survival of patients aged younger than 55 years was 49.2%, and 28.2% for patients aged over 55 years (p = 0.04). Patients with nonserous histology had significantly longer one year overall survival compared to serous histology (61.4% vs 29.8%) (p = 0.01). Conclusion: The brain is one of the rarest locations for ovarian cancer metastasis. Radiotherapeutic approaches are the mainstay of treatment but survival rates are low. Age and tumor histology were determined as significant parameters that affected survival rates.

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“…A next-generation sequencing-based genomic analysis of eight OC BMs exhibited BRCA1/2 mutations in 7/8 cases, and all samples showed mutations in at least one gene involved in DNA repair (BRCA1/2, ATM, CHEK2) [72]. Furthermore, two authors demonstrated a high prevalence of BRCA1 protein loss in patients with BMs from OC [73,74].…”

Section: Pathology and Molecular Profilingmentioning

confidence: 93%

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis

Borella

Bertero

Morrone

et al. 2020

Cancers

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With this review, we provide the state of the art concerning brain metastases (BMs) from ovarian cancer (OC), a rare condition. Clinical, pathological, and molecular features, treatment options, and future perspectives are comprehensively discussed. Overall, a diagnosis of high-grade serous OC and an advanced disease stage are common features among patients who develop brain metastases. BRCA1 and BRCA2 gene mutations, as well as the expression of androgen receptors in the primary tumor, are emerging risk and prognostic factors which could allow one to identify categories of patients at greater risk of BMs, who could benefit from a tailored follow-up. Based on present data, a multidisciplinary approach combining surgery, radiotherapy, and chemotherapy seem to be the best approach for patients with good performance status, although the median overall survival (<1 year) remains largely disappointing. Hopefully, novel therapeutic avenues are being explored, like PARP inhibitors and immunotherapy, based on our improved knowledge regarding tumor biology, but further investigation is warranted.

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Significance of BRCA1 expression in breast and ovarian cancer patients with brain metastasis – A multicentre study

Cited by 10 publications

References 29 publications

Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

The clinical outcomes of ovarian cancer in patients with brain metastasis

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis

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