Abstract 115P
Background
MicroRNAs (miRNAs) are small noncoding RNAs primarily involved in RNA silencing and post-transcriptional regulation of gene expression. Although miRNAs regulate angiogenesis during normal physiological processes, their aberrant expression may promote angiogenesis during tumor progression. This prospective study aimed to investigate the role of miRNAs 27a,27b, 107 and 622 in colorectal cancer (CRC).
Methods
Patients with early-stage or de novo metastatic CRC (mCRC) eligible for oxaliplatin/capecitabine chemotherapy +/- bevacizumab were included in the study. Blood samples were collected on day 1, at 3 and 6 months and following RNA extraction, miRNAs analysis was performed by RT-PCR (Agilent Technologies, Santa Clara, USA, miRCURY LNA SYBR Green PCR kit Qiagen, Maryland, USA). MiRNA levels were analysed in relation to clinicopathologic characteristics [age, stage, histologic grade, molecular profile (KRAS, NRAS, BRAF, MSI), sideness and site of metastasis], therapies, and outcomes. Statistical analysis was conducted using Fisher’s exact, Mann-Whitney and Kaplan-Meier tests (STATA/MP 16.0 for Windows).
Results
Of 101 patients, 58 were males, 22 were treated with adjuvant and 79 with first-line therapy. The median follow-up time was 35 months (10.9-38.7). The mPFS and the mOS were 9.1 (6.4-11.8) and 28.2 (16.0-40.4) months respectively. The baseline levels of miRNAs 27a,27b, 107 and 622 were statistically significantly lower in patients with mCRC than those with resected tumors. Of patients with mCRC, those with mucinous adenocarcinoma had a trend for increased miRNA107 levels (p=0.062) and those with BRAFV600 mutation exhibited significantly higher levels of all miRNAs [miRNAs 27a (p=0.001),27b (p=0.003), 107 (p=0.003) and 622 (p=0.011)]. Higher levels of miRNA 27a, 27b, 107 and 622 before treatment in mCRC were associated with worse prognosis (p=0.118. p=0.118, p=0.013; p=0.042). Although levels of all miRNAs dropped during chemotherapy treatment, high levels of miRNA 622 at 6 months of treatment in mCRC were associated with an increased risk of death (p=0.007).
Conclusions
Our findings affirm the presence of a distinct and evolving miRNA signature throughout the progression and treatment of CRC.
Legal entity responsible for the study
The authors.
Funding
Hellenic Society of Medical Oncology.
Disclosure
A. Koumarianou: Financial Interests, Institutional, Research Grant: Merck. All other authors have declared no conflicts of interest.