A specific miRNA signature correlates with complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1113-9. doi: 10.1016/j.ijrobp.2011.09.030. Epub 2011 Dec 13.

Abstract

Purpose: MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific "signature" correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy.

Methods and materials: A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study.

Results: Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909∗, miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases.

Conclusions: A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Capecitabine
  • Chemoradiotherapy, Adjuvant / methods*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Male
  • MicroRNAs / analysis*
  • Microarray Analysis / methods
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • RNA, Neoplasm / analysis*
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Rectum / chemistry
  • Rectum / pathology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sensitivity and Specificity

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • Organoplatinum Compounds
  • RNA, Neoplasm
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil