Five microRNAs in Serum Are Able to Differentiate Breast Cancer Patients From Healthy Individuals

Feliciano, Andrea; Gonzalez, Lucila; García-Mayea, Yoelsis; Mir, Cristina; Artola, Mireia; Barragán, Nieves; Martín, Remedios; Altés, Anna; Castellví, Josep; Benavente, Sergio; Cajal, Santiago Ramón y; Espinosa-Bravo, Martín; Cortés, Javier; Rubio, Isabel T.; Lleonart, Matilde E.

doi:10.3389/fonc.2020.586268

Cited by 19 publications

(13 citation statements)

References 42 publications

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“…These findings underscore the link between miR-200 and metastatic spread and indicate them as markers for early detection of metastatic disease and prognosis. However, this assertion is tempered by results of recent investigation of serum markers of breast cancer that included miR-200 members in its list of interrogated miRNAs, which indicated an association between high serum levels of miR-141 and better survival [ 135 ]. This study also proposed a 5-miRNA panel for serum-based detection of breast cancer which however did not include miR-141 or other miR-200 members [ 135 ].…”

Section: Circulating Mir-200 As Biomarkersmentioning

confidence: 99%

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cavallari

Ciccarese

Sharova

et al. 2021

Cancers

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The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.

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Section: Circulating Mir-200 As Biomarkersmentioning

confidence: 99%

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cavallari

Ciccarese

Sharova

et al. 2021

Cancers

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“…It was upregulated and associated with poor survival in metastatic breast cancer patients particularly in those with TNBC (29), but, on the other hand, it is among the most potent miRNAs repressing cell growth and counteracting estradiol-dependent cell proliferation (30). In our study a greater expression of miR-181a was positively associated with long-term fulvestrant bene t. Also on miR-16-5p literature data are somehow inconsistent since preclinical data support tumor suppressive properties but an increased expression in TNBC as compared to normal tissues has been found as well as either a down-or upregulation in the serum of breast cancer patients as compared to healthy controls (33,(35)(36)(37). In our study miR-16-5p was associated with a decreased probability of being progression-free at 18 months.…”

Section: Discussionmentioning

confidence: 59%

“…In our study we identi ed 9 miRNAs which were signi cantly and differently associated with 18-month PFS. Literature data provide evidence about 3 of these miRNAs (let-7c, miR-520d-3p, miR-181a) to be involved in HR+ABC (30)(31)(32)(33)(34)(35). In particular miR-520d-3p was among miRNAs which were downregulated upon estradiol stimulation in BCCL (30).…”

Section: Discussionmentioning

confidence: 96%

Clinical, pathological and molecular predictors of Fulvestrant long-term benefit in Hormone Receptor-positive / HER2 negative advanced breast cancer

Torrisi

Vaira

Giordano

et al. 2022

Preprint

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Purpose: The identification of factors predicting the benefit of treatments is a major goal for medical oncologists. Methods We retrospectively investigated in metastatic tumor tissues of women treated with fulvestrant for HR+/HER2 negative advanced breast cancer clinical, pathological and molecular features associated with long-term benefit from treatment defined as being progression-free at 18 months. Specifically, we analyzed ESR1 and PI3KCA mutations and miRNA profiles.Results: Fifty-nine patients were evaluable (median age 67 yrs, range 32-92). Overall mPFS was 10.7 months (range 2.2-14) while 18-month PFS rate was 27%; only the lack of visceral metastases significantly predicted the likelihood of being progression-free at 18 months (OR=0.25 95%CI 0.07-0.9 p=.035). PI3KCA mutations were found in 36% of patients and were associated with a numerically shorter mPFS but not with a lower likelihood of being progression-free at 18 months. As of miRNAs, miR-549a, miR-644a, miR-16-5p were negatively associated with 18-month PFS while let-7c-5p was positively associated with outcome. In addition, miR-520d-3p and miR-548g-3p values were significantly lower while miR-603, miR-181a and miR-199a-miR-199b-3p values were significantly higher in patients achieving 18-month PFS. In silico analysis of predicted targets suggested that miR-520d-3p and miR-548g-3p decrease might induce Hippo and Wnt signaling, while high levels of miR-603, mir-181a-5p,miR-199a-miR-199b-3p might repress endocrine resistance thus potentially promoting the response to treatment. Conclusions: Our clinical findings are consistent with literature data, while the mutation and miRNA results provide some clues on the molecular mechanisms involved in fulvestrant activity and resistance to be confirmed in larger cohorts of breast cancer patients.

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“…In our study we identified 9 miRNAs which were significantly and differently associated with 18-month PFS. Literature data provide evidence about 3 of these miRNAs (let-7c, miR-520d-3p, miR-181a) to be involved in HR+ ABC [30][31][32][33][34][35] . In particular miR-520d-3p was among miRNAs which were downregulated upon estradiol stimulation in BCCL 30 .…”

Section: Discussionmentioning

confidence: 99%

“…In our study a greater expression of miR-181a was positively associated with long-term fulvestrant benefit. Also on miR-16-5p literature data are somehow inconsistent since preclinical data support tumor suppressive properties but an increased expression in triple negative breast cancer (TNBC) as compared to normal tissues has been found as well as either a down-or upregulation in the serum of breast cancer patients as compared to healthy controls 33,[35][36][37] . In our study miR-16-5p was associated with a decreased probability of being progressionfree at 18 months.…”

Section: Discussionmentioning

confidence: 99%

Predictors of fulvestrant long-term benefit in hormone receptor-positive/HER2 negative advanced breast cancer

Torrisi

Vaira

Giordano

et al. 2022

Sci Rep

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We retrospectively investigated in women treated with fulvestrant for HR+/HER2 negative advanced breast cancer clinical, pathological and molecular features associated with long-term benefit from treatment defined as being progression-free at 18 months. Specifically, we analyzed on formalin-fixed paraffin-embedded tumor samples ESR1 and PI3KCA mutations and miRNAs profiles. 59 patients were evaluable (median age of 67 years, range 32–92). 18-month PFS rate was 27%; the lack of visceral metastases significantly predicted the likelihood of being progression-free at 18 months, while PI3KCA mutations, found in 36% of patients, were not associated with 18-month PFS. As of miRNAs, miR-549a, miR-644a, miR-16-5p were negatively while let-7c-5p was positively associated with 18-month PFS. In addition, miR-520d-3p and miR-548g-3p values were significantly lower while miR-603, miR-181a-5p and miR-199a-miR-199b-3p values were significantly higher in patients achieving 18-month PFS. In silico analysis of targets modulated by these two latter groups of miRNAs show that in patients achieving 18-month PFS the Hippo and Wnt signaling pathways were predicted to be upregulated while endocrine resistance was potentially repressed by miR-603, miR-181a-5p and miR-199a-miR-199b-3p. Our results provide additional clues on the molecular mechanisms involved in fulvestrant activity and resistance. Underlying pathways should be further elucidated and confirmed in larger cohorts.

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Five microRNAs in Serum Are Able to Differentiate Breast Cancer Patients From Healthy Individuals

Cited by 19 publications

References 42 publications

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Clinical, pathological and molecular predictors of Fulvestrant long-term benefit in Hormone Receptor-positive / HER2 negative advanced breast cancer

Predictors of fulvestrant long-term benefit in hormone receptor-positive/HER2 negative advanced breast cancer

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