Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer.
BACKGROUND
Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients' prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options.


METHODS
Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage. Quantitative real-time polymerase chain reaction (qPCR) was performed on an independent set of 147 rectal cancer patients to validate relevant miRNAs.


RESULTS
In the microarray screen, 14 microRNAs were significantly correlated to overall survival. Five microRNAs were included from previous work. Finally, 19 miRNAs were evaluated by qPCR. miR-515-5p, miR-573, miR-579 and miR-802 demonstrated significant correlation with overall survival and cancer-specific survival (p < 0.05). miR-573 was also significantly correlated with the tumor regression grade after preoperative chemoradiotherapy. miR-133b showed a significant correlation with distant-metastasis-free survival. miR-146b expression levels showed a significant correlation with nodal stage.


CONCLUSIONS
Specific microRNAs can be used as biomarkers to predict prognosis of patients with rectal cancer and possibly stratify patients' therapy if validated in a prospective study.
Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. azadeh.azizian@med.uni-goettingen.de.
Azadeh
A
Azizian
Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. ingo-epping@web.de.
Ingo
I
Epping
Department of Medical Statistics, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. frank.kramer@med.uni-goettingen.de.
Frank
F
Kramer
Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. jo.peter@chirurgie-goettingen.de.
Peter
P
Jo
Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. markus.bernhardt@med.uni-goettingen.de.
Markus
M
Bernhardt
Department of Pathology, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. j.kitz@med.uni-goettingen.de.
Julia
J
Kitz
Department of Developmental Biochemistry, University of Göttingen, Göttingen 37075, Germany. gsalina@gwdg.de.
Gabriela
G
Salinas
Medical Practice Radiotherapy München, Burgstraße 7, München 80331, Germany. hendrik.wolff@med.uni-goettingen.de.
Hendrik A
HA
Wolff
Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. marian.grade@med.uni-goettingen.de.
Marian
M
Grade
Department of Medical Statistics, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. tim.beissbarth@med.uni-goettingen.de.
Tim
T
Beißbarth
Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. mghadim@uni-goettingen.de.
B Michael
BM
Ghadimi
Department of General, Visceral, and Pediatric Surgery, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany. jochen.gaedcke@med.uni-goettingen.de.
Jochen
J
Gaedcke
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D012007:Rectum / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D035683:MicroRNAs
biomarkers; chemoradiotherapy; miRNA; prognosis; rectal cancer; tumor regression grade