Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers

Boukerroucha, Meriem; Josse, Claire; ElGuendi, Sonia; Boujemla, Bouchra; Freres, Pierre; Marée, Raphaël; Wenric, Stéphane; Segers, Karin; Collignon, Joëlle; Jérusalem, Guy

doi:10.1186/s12885-015-1740-9

Cited by 22 publications

(14 citation statements)

References 40 publications

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“…miRNAs are small non-coding RNAs that bind to the 3' untranslated (3'UTR) region of target messenger RNAs (mRNAs); they are known to regulate gene expression and are frequently deregulated in BC. Different miRNAs, such as miR-146, 218, 335, 342, 498, 548, or 638, regulate BRCA1 mRNA expression, and could contribute to the population of IHC BRCA1-negative tumors [63,[67][68][69][70]. A critical comprehensive appraisal of these additional factors influencing BRCA1 expression is necessary, in order to better define the tumor population sensitive to CT. Additional efforts are necessary to determine the potential impact of additional events, such as loss of heterozygosity, on the population exhibiting BRCA1 promoter hypermethylation [32].…”

Section: Discussionmentioning

confidence: 99%

BRCA1 Promoter Hypermethylation is Associated with Good Prognosis and Chemosensitivity in Triple-Negative Breast Cancer

Jacot

Lopez-Crapez

Mollévi

et al. 2020

Cancers

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The aberrant hypermethylation of BRCA1 promoter CpG islands induces the decreased expression of BRCA1 (Breast Cancer 1) protein. It can be detected in sporadic breast cancer without BRCA1 pathogenic variants, particularly in triple-negative breast cancers (TNBC). We investigated BRCA1 hypermethylation status (by methylation-specific polymerase chain reaction (MS-PCR) and MassARRAY® assays), and BRCA1 protein expression using immunohistochemistry (IHC), and their clinicopathological significance in 248 chemotherapy-naïve TNBC samples. Fifty-five tumors (22%) exhibited BRCA1 promoter hypermethylation, with a high concordance rate between MS-PCR and MassARRAY® results. Promoter hypermethylation was associated with reduced IHC BRCA1 protein expression (p = 0.005), and expression of Programmed death-ligand 1 protein (PD-L1) by tumor and immune cells (p = 0.03 and 0.011, respectively). A trend was found between promoter hypermethylation and basal marker staining (p = 0.058), and between BRCA1 expression and a basal-like phenotype. In multivariate analysis, relapse-free survival was significantly associated with N stage, adjuvant chemotherapy, and histological subtype. Overall survival was significantly associated with T and N stage, histology, and adjuvant chemotherapy. In addition, patients with tumors harboring BRCA1 promoter hypermethylation derived the most benefit from adjuvant chemotherapy. In conclusion, BRCA1 promoter hypermethylation is associated with TNBC sensitivity to adjuvant chemotherapy, basal-like features and PD-L1 expression. BRCA1 IHC expression is not a good surrogate marker for promoter hypermethylation and is not independently associated with prognosis. Association between promoter hypermethylation and sensitivity to Poly(ADP-ribose) polymerase PARP inhibitors needs to be evaluated in a specific series of patients.

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Section: Discussionmentioning

confidence: 99%

BRCA1 Promoter Hypermethylation is Associated with Good Prognosis and Chemosensitivity in Triple-Negative Breast Cancer

Jacot

Lopez-Crapez

Mollévi

et al. 2020

Cancers

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“…MiR-548c was reported to be an independent prognostic factor for breast cancer. Patients with a good prognosis presented higher intratumoral expression of miR-548c [ 41 ]. Consistently, our meta-analysis suggested that high expression of miR-548c in EC and OC appears to correlate with better survival in patients with EC and OC, implying that miR-548c may be a new promising prognostic factor in these cancers.…”

Section: Discussionmentioning

confidence: 99%

MiR-548c impairs migration and invasion of endometrial and ovarian cancer cells via downregulation of Twist

Sun

Cui

Zhang

et al. 2016

J Exp Clin Cancer Res

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BackgroundMicroRNAs (miRNAs) are a class of small non-coding RNAs, which post-transcriptionally repress the expression of genes involved in cancer initiation and progression. Although some miRNAs that target many signaling pathways (also called universe miRNAs) are supposed to play a global role in diverse human tumors, their regulatory functions in gynecological cancers remain largely unknown. We investigated the biological role and underlying mechanism of miR-548c (one universe miRNA) in endometrial and ovarian cancer.MethodsThe effects of miR-548c overexpression on cell proliferation, migration and invasion were studied in endometrial and ovarian cancer cells. TWIST1 (Twist) was identified as a direct miR-548c target by western blot analysis and luciferase activity assay. The expression of miR-548c and Twist were examined by qRT-PCR in endometrial and ovarian cancer tissues.ResultsHere, we report that miR-548c is down-regulated in endometrial and ovarian cancer tissues when compared to normal tissues, and our meta-analysis reveal that decreased miR-548c expression correlates with poor prognosis in endometrial cancer patients. We show that in endometrial and ovarian cancer cells, ectopic expression of miR-548c significantly inhibits whereas knockdown of miR-548c dramatically induces cancer cell proliferation, migration and invasion. By using luciferase reporter assay, we demonstrate that Twist, a known oncogene in endometrial and ovarian cancers, is a direct target of miR-548c. Furthermore, the expression of Twist partially abrogates the tumor suppressive effects of miR-548c on cell migration and invasion.ConclusionThese findings suggest that miR-548c directly downregulates Twist, and provide a novel mechanism for Twist upregulation in both endometrial and ovarian cancers. The use of miR-548c may hold therapeutic potential for the treatment of Twist-overexpressing tumors.

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“…27 Previous studies have indicated that MiR-548c-5p served as a prognostic biomarker for triplenegative breast cancers. 28 MiR-548c-5p also served as a suppressor for primary liver cancer by regulating the proliferation, migration, and invasion of liver cancer cells. 29 In our study, miR-548c-5p is the most significantly downregulated DEmiRNA covering the most DEGs in COAD which supported previous studies.…”

Section: Discussionmentioning

confidence: 99%

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing

Liu

et al. 2017

Tumour Biol.

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Colon adenocarcinoma is the third leading cause of cancer-related deaths across the world, developing novel and non-invasive diagnostic and prognostic biomarkers for the early-stage colon adenocarcinoma at molecular level is essential. In our study, RNA-sequencing was performed to identify the differentially expressed genes and miRNAs (DEmiRNAs) in early-stage colon adenocarcinoma compared to tissues of precancerous lesions, colonic intraepithelial neoplasia. The DEmiRNA-target interaction network was constructed and functional annotation of targets of DEmiRNAs was performed. The Cancer Genome Atlas was used to verify the expression of selected differentially expressed genes. The receiver operating characteristic analyses of selected differentially expressed genes was performed. In total, 865 differentially expressed genes, 26 DEmiRNAs, and 329 DEmiRNA-target pairs were obtained. Based on the early-stage colon adenocarcinoma network, miR-548c-5p, miR-548i, and miR-548am-5p were the top three DEmiRNAs that covered most differentially expressed genes. NTRK2, DTNA, and BTG2 were the top three differentially expressed genes regulated by most DEmiRNAs. Cancer and colorectal cancer pathways were two significantly enriched pathways in early-stage colon adenocarcinoma. The common differentially expressed genes in both the pathways were AXIN2, Smad2, Smad4, PIK3R1, and BCL2. The expression levels of eight differentially expressed genes (NTRK2, DTNA, BTG2, COL11A1, Smad2, Smad4, PIK3R1, and BCL2) in The Cancer Genome Atlas database were compatible with our RNA-sequencing. All these eight differentially expressed genes and AXIN2 had the potential diagnosis value for Colon adenocarcinoma. In conclusion, a total of ten differentially expressed genes (NTRK2, DTNA, BTG2, COLCA1, COL11A1, AXIN2, Smad2, Smad4, PIK3R1, and BCL2) and four DEmiRNAs (miR-548c-5p, miR-548i, mir-424-5p, and miR-548am-5p) may be involved in the pathogenesis of early-stage colon adenocarcinoma which may make a contribution for developing new diagnostic and therapeutic strategies for early-stage colon adenocarcinoma.

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Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers

Cited by 22 publications

References 40 publications

BRCA1 Promoter Hypermethylation is Associated with Good Prognosis and Chemosensitivity in Triple-Negative Breast Cancer

BRCA1 Promoter Hypermethylation is Associated with Good Prognosis and Chemosensitivity in Triple-Negative Breast Cancer

MiR-548c impairs migration and invasion of endometrial and ovarian cancer cells via downregulation of Twist

Screening key genes and miRNAs in early-stage colon adenocarcinoma by RNA-sequencing

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