Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy

Ruth Louise Vinall, Clifford G Tepper, Alexandra A.Z. Ripoll, Regina F Gandour-Edwards, Blythe P. Durbin-Johnson, Stanley Yap, Paramita M Ghosh, Ralph W deVere White

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo-responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)). Microarray and qPCR identified let-7c as being differentially expressed in chemo-responder versus non-responder patients. Patients with higher let-7c expression levels had significantly higher odds of responding to chemotherapy (p = 0.023, OR 2.493, 95% CI 1.121, 5.546), and assessment of let-7c levels allowed for prediction of patient response (AUC 0.72, positive predictive value 59%). Decreased let-7c was associated with MIBC incidence (p < 0.001), and significantly correlated with other related miRNA including those that were not differentially expressed between responders and non-responders. The combined data indicate let-7c plays a role in mediating chemoresistance to neoadjuvant chemotherapy in MIBC patients, and is a modest, yet clinically meaningful, predictor of patient response.

Original languageEnglish (US)
Pages (from-to)86-97
Number of pages12
JournalGenes and Cancer
Volume7
Issue number3-4
DOIs
StatePublished - Mar 1 2016

Fingerprint

Urinary Bladder Neoplasms
Drug Therapy
Muscles
MicroRNAs
Survival Rate
Area Under Curve
Biomarkers
RNA
Biopsy
Polymerase Chain Reaction
Incidence

Keywords

  • Chemoresistance
  • Let-7c
  • MiRNA
  • Muscle invasive bladder cancer
  • Neoadjuvant chemotherapy

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy. / Vinall, Ruth Louise; Tepper, Clifford G; Ripoll, Alexandra A.Z.; Gandour-Edwards, Regina F; Durbin-Johnson, Blythe P.; Yap, Stanley; Ghosh, Paramita M; deVere White, Ralph W.

In: Genes and Cancer, Vol. 7, No. 3-4, 01.03.2016, p. 86-97.

Research output: Contribution to journalArticle

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