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. 2020 Sep-Oct;17(5):605-613.
doi: 10.21873/cgp.20217.

Association of miR-125b, miR-17 and let-7c Dysregulations With Response to Anti-epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With Metastatic Colorectal Cancer

Ondrej Fiala  1   2 , Ondrej Sorejs  3   2 , Petr Hosek  2 , Vaclav Liska  2   4 , Ondrej Vycital  4 , Jan Bruha  4 , Radek Kucera  5 , Ondrej Topolcan  5 , Jindrich Finek  3 , Diana Maceckova  2 , Pavel Pitule  2
Affiliations

Association of miR-125b, miR-17 and let-7c Dysregulations With Response to Anti-epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With Metastatic Colorectal Cancer

Ondrej Fiala et al. Cancer Genomics Proteomics. 2020 Sep-Oct.

Abstract

Background/aim: MicroRNAs (miRs) play an important role in the regulation of cancer-related processes and are promising candidates for cancer biomarkers. The aim of the study was to evaluate the association of response to anti-EGFR monoclonal antibodies (mAbs) with selected miR expression profiles, including miR-125b, let-7c, miR-99a, miR-17, miR-143 and miR-145 in metastatic colorectal cancer (mCRC) patients.

Patients and methods: This retrospective study included 46 patients with mCRC harbouring wild-type RAS gene treated with cetuximab or panitumumab combined with chemotherapy in first- or second-line therapy. The miR expression was assessed using qRT-PCR.

Results: Down-regulation of miR-125b and let-7c and up-regulation of miR-17 were found in the tumour tissue (p=0.0226, p=0.0040, p<0.0001). Objective response rate (ORR) was associated with up-regulation of miR-125b (p=0.0005). Disease control rate (DCR) was associated with up-regulation of miR-125b and let-7c (p=0.0383 and p=0.0255) and down-regulation of miR-17 (p=0.0464). MiR-125b showed correlation with progression-free and overall survival (p=0.055 and p=0.006).

Conclusion: The results show that up-regulation of miR-125b is associated with higher ORR and DCR and longer survival; let-7c up-regulation and miR-17 down-regulation are associated with higher DCR in mCRC patients treated with anti-EGFR mAbs.

Keywords: Colorectal cancer; cetuximab; chemotherapy; let-7c; miR-125b; miR-17; microRNA; panitumumab.

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Conflict of interest statement

OF received honoraria from Roche, GSK and Pfizer for consultations and lectures unrelated to this project. JF has received honoraria from Astra Zeneca, Roche and Novartis for consultations and lectures unrelated to this project. OS, PH, VL, OV, JB, RK, OT, DM and PP declare that they have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence this work.

Figures

Figure 1
Figure 1. The differential expression levels of assessed miRs between tumour and adjacent non-tumour tissues.
Figure 2
Figure 2. The association of differential expression levels of miR-125b with objective response (A), miR-125b with disease control (B), miR-17 with disease control (C) and let-7c with disease control (D).
Figure 3
Figure 3. Progression-free survival (PFS) (A) and overall survival (OS) (B) according to miR-125b differential expression levels using automated optimization of stratification threshold value of 4.5-fold decrease of miR-125b levels in tumour tissue.
See this image and copyright information in PMC

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