miR‐125b‐1 and miR‐378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer

Abstract

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse‐transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR‐125b‐1 in cancer cells (P = 0.040), and miR‐378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR‐378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027–7.585; P = 0.044). In conclusion, miR‐125b‐1 and miR‐378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.

Plasma exosomal microRNA‑125b as a monitoring biomarker of resistance to mFOLFOX6‑based chemotherapy in advanced and recurrent colorectal cancer patients

“…D'Angelo et al reported that high miR-125b expression in tissue and serum was associated with a poor treatment response in locally advanced rectal cancer (30). Interestingly, Tanaka et al identified miR-125b-1 expression in cancer tissues as a predictive biomarker for the efficacy of peptide vaccine treatment against CRC (31). However, our study is the first to demonstrate the potential of plasma ex-miR-125b as a biomarker for the early detection of resistance to mFOLFOX6-based chemotherapy in advanced/recurrent CRC.…”

Trial watch: Peptide-based vaccines in anticancer therapy

“…118 The field is therefore moving along three non-mutually exclusive directions: (1) combining peptide-based vaccination with additional forms of (immuno)therapy, with the specific aim of reverting immunosuppression and enabling therapeutically relevant immune responses, 270-272 (2) targeting private antigenic epitopes that originate from mutations affecting only malignant cells (or sub-populations thereof), with PPV, 167,272-275 and (3) identifying specific patient populations that may obtain clinical benefit from the use of peptide-based vaccination. 174,254 Although the feasibility of PPV on a large scale remains unclear, we surmise combining some variants of peptide-based vaccination with potent immunostimulatory agents including immune checkpoint blockers and oncolytic viruses may be the key to unlock the true potential of this hitherto unrealized therapeutic modality.…”

Anticancer effect of HOTTIP regulates human pancreatic cancer via the metabotropic glutamate receptor 1 pathway

“…The specific function of them determines whether or not cells undergo apoptosis. To a certain extent, apoptosis or apoptosis inhibition is determined by gene regulation (20).…”