Let-7 miRNA's Expression Profile and Its Potential Prognostic Role in Uterine Leiomyosarcoma

Author(s)

de Almeida, Bruna Cristine ^[1] ; dos Anjos, Laura Gonzalez ^[1] ; Uno, Miyuki ^[2] ; da Cunha, Isabela Werneck ^{[3, 4, 5]} ; Soares, Fernando Augusto ^{[3, 4, 5]} ; Baiocchi, Glauco ^[6] ; Baracat, Edmund Chada ^[1] ; Carvalho, Katia Candido ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Obstet & Ginecol, Lab Ginecol Estrutural & Mol LIM 58, Disciplina Ginecol, Hosp Clin, Fac Med, BR Av Dr Arnaldo 455, Sala 4121, BR-05403010 Sao Paulo, SP - Brazil

^[2] Inst Canc Estado Sao Paulo CTO ICESP, Ctr Invest Translac Oncol LIM 24, Av Dr Arnaldo 251 Sala 23 8 Andar, BR-01246000 Sao Paulo, SP - Brazil

^[3] Rede DOR Sao Luiz, Dept Pathol, Rua Perobas, 344 Jabaquara, BR-04321120 Sao Paulo, SP - Brazil

^[4] Hosp AC Camargo Canc Ctr, BR R Tamandare 753, BR-05403010 Sao Paulo, SP - Brazil

^[5] Natl Inst Sci & Technol Oncogen & Therapeut Innov, BR R Tamandare 753, BR-05403010 Sao Paulo, SP - Brazil

^[6] AC Camargo Canc Ctr, Dept Gynecol Oncol, Rua Prof Antonio Prudente 211, BR-01509001 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 8, n. 11 NOV 2019.
• Web of Science Citations: 0

Abstract

The lethal-7 (let-7) family is an important microRNA (miRNA) group that usually exerts functions as a tumor suppressor. We aimed to evaluate the expression profile of let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i and to assess their value as prognostic markers in uterine leiomyosarcoma (LMS) patients. The miRNAs expression profile was assessed in 34 LMS and 13 normal myometrium (MM) paraffin-embedded samples. All let-7 family members showed downregulation in LMS. Our findings showed that patients with let-7e downregulation had worse overall survival (OS) and is an independent prognostic factor (hazard ratio {[}HR] = 2.24). In addition, almost half the patients had distant metastasis. LMS patients with downregulated let-7b and let-7d had worse disease-free survival (DFS); they are not independent prognostic factors (HR = 2.65). Patients' ages were associated with let-7d, let-7e and let-7f (p = 0.0160) downregulation. In conclusion, all the let-7 family members were downregulated in LMS patients, and the greater the loss of expression of these molecules, the greater their relationship with worse prognosis of patients. Let-7e expression might influence the OS, while let-7b and le-7d might influence the DFS. The lowest expression levels of let-7d, let-7e, and let-7f were associated with the oldest patients. Our findings indicate strong evidence of let-7's role as a potential prognostic biomarker in LMS. (AU)

• FAPESP's process: 12/23652-0 - Molecular analysis of the mechanisms involved in the regulation of EGF, VEGF, HER2 and of the transcriptional factor Foxo3 expression in uterine sarcoma
• Grantee: Kátia Cândido Carvalho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/01109-2 - Genetic and epigenetic features of the uterine smooth muscle tumors: identification of molecular markers
• Grantee: Kátia Cândido Carvalho
• Support Opportunities: Regular Research Grants