Changes in circulating microRNA-126 during treatment with chemotherapy and bevacizumab predicts treatment response in patients with metastatic colorectal cancer

• Published in: British journal of cancer Vol. 112; no. 4; pp. 624 - 629
• Main Authors: Hansen, T F, Carlsen, A L, Heegaard, N H H, Sørensen, F B, Jakobsen, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17-02-2015; Nature Publishing Group
• Subjects: 631/337/384/331; 692/699/67/1059/2325; 692/699/67/1059/99; 692/699/67/1504/1885; Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Cancer Research; Clinical Study; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug Resistance; Epidemiology; Female; Fluorouracil - analogs & derivatives; Fluorouracil - therapeutic use; Humans; Male; MicroRNAs - blood; Middle Aged; Molecular Medicine; Neoadjuvant Therapy; Neoplasm Metastasis; Oncology; Predictive Value of Tests; Treatment Outcome; colorectal cancer; microvesicles; microRNA-126; chemotherapy; angiogenesis; predictive markers
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.652

Background:
This study investigated the predictive value of circulating microRNA-126 (cir-miRNA-126) in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy combined with bevacizumab.
Methods:
The study included 68 patients. Blood samples (plasma) were collected before the treatment initiation, at the first clinical evaluation after 3 weeks and at progression. Levels of cir-miRNA-126 were determined by qRT–PCR after purification of total RNA from plasma. Primary clinical end points were response rates evaluated according to the Response Evaluation Criteria In Solid Tumours (RECIST) and progression-free survival (PFS).
Results:
Changes in circulating miRNA-126 during treatment were predictive of tumour response. Non-responding patients had a median increase in cir-miRNA-126 of 0.244 (95% confidence interval (CI), 0.050–0.565) compared with a median decrease of −0.374 (95% CI, −0.472 to −0.111) in the responding patients,
P
=0.002. A significant positive correlation was demonstrated by comparing the changes in tumour size with the changes in cir-miRNA-126,
r
=0.48,
P
=0.0001. Grouping the patients according to the changes in cir-miRNA-126 disclosed a borderline significant separation of the groups in the PFS analysis favouring patients with decreasing miRNA-126 levels, hazard ratio (HR) 0.60 (95% CI, 0.33–1.09),
P
=0.07.
Conclusions:
The present results indicate that changes in cir-miRNA-126 during treatment are related to the response to chemotherapy and bevacizumab in patients with mCRC, thus representing a possible biomarker for the resistance to anti-angiogenic containing treatments.