title: MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients.
abstract: BACKGROUND
  Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy with fluoropyrimidines (capecitabine or 5-fluorouracil) followed by radical surgical resection. Unfortunately, a significant proportion of tumors do not respond enough to the neoadjuvant treatment and these patients are at risk of relapse. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers for rectal cancer patients.
  
  
  METHODS
  We selected 20 patients who underwent neoadjuvant chemoradiotherapy for advanced rectal cancer and whose tumors were classified as most sensitive or resistant to the treatment. These two groups were compared using large-scale miRNA expression profiling.
  
  
  RESULTS
  Expression levels of 8 miRNAs significantly differed between two groups. MiR-215, miR-190b and miR-29b-2* have been overexpressed in non-responders, and let-7e, miR-196b, miR-450a, miR-450b-5p and miR-99a* have shown higher expression levels in responders. Using these miRNAs 9 of 10 responders and 9 of 10 non-responders (p < 0.05) have been correctly classified.
  
  
  CONCLUSIONS
  Our pilot study suggests that miRNAs are part of the mechanisms that are involved in response of rectal cancer to the chemoradiotherapy and that miRNAs may be promising predictive biomarkers for such patients. In most miRNAs we identified (miR-215, miR-99a*, miR-196b, miR-450b-5p and let-7e), the connection between their expression and radioresistance or chemoresistance to inhibitors of thymidylate synthetase was already established.
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 656 53, Czech Republic. msvoboda@mou.cz
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.forename: Jiri
authors.initials: J
authors.lastname: Sana
authors.forename: Pavel
authors.initials: P
authors.lastname: Fabian
authors.forename: Ilona
authors.initials: I
authors.lastname: Kocakova
authors.forename: Jana
authors.initials: J
authors.lastname: Gombosova
authors.forename: Jana
authors.initials: J
authors.lastname: Nekvindova
authors.forename: Lenka
authors.initials: L
authors.lastname: Radova
authors.forename: Rostislav
authors.initials: R
authors.lastname: Vyzula
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D000069287:Capecitabine; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D010865:Pilot Projects; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D003841:Deoxycytidine; D000069287:Capecitabine; D013940:Thymidylate Synthase; D005472:Fluorouracil