A Tumor and Immune-Related Micro-RNA Signature Predicts Relapse-Free Survival of Melanoma Patients Treated with Ipilimumab

Abstract

Despite the unprecedented advances in the treatment of melanoma with immunotherapy, there continues to be a major need for biomarkers of clinical benefits and immune resistance associated with immune checkpoint inhibitors; microRNA could play a vital role in these efforts. This study planned to identify differentially expressed miRNA molecules that may have prognostic value for clinical benefits. Patients with surgically operable regionally advanced melanoma were treated with neoadjuvant ipilimumab (10 mg/kg intravenously every 3 weeks × two doses) bracketing surgery. Tumor biospecimens were obtained at baseline and surgery, and microRNA (miRNA) expression profiling was performed on the tumor biopsies. We found that an expression profile consisting of a 4-miRNA signature was significantly associated with improved relapse-free survival (RFS). The signature consisted of biologically relevant molecules previously reported to have prognostic value in melanoma and other malignancies, including miR-34c, miR-711, miR-641, and miR-22. Functional annotation analysis of target genes for the 4-miRNA signature was significantly enriched for various cancer-related pathways, including cell proliferation regulation, apoptosis, the MAPK signaling pathway, and the positive regulation of T cell activation. Our results presented miRNAs as potential biomarkers that can guide the treatment of melanoma with immune checkpoint inhibitors. These findings warrant further investigation in relation to CTLA4 blockade and other immune checkpoint inhibitors. ClinicalTrials.gov NCT00972933.

Treatment of Stage III Resectable Melanoma—Adjuvant and Neoadjuvant Approaches

“…With regard to gene expression profiling, a recent study reported a 4-miRNA signature, the baseline expression levels of which were significantly associated with the therapeutic benefits of neoadjuvant ipilimumab. 105 Biomarkers that have been explored in clinical trials of neoadjuvant therapy are summarized in Table 3 per each treatment strategy.…”

miRNA-Based Technologies in Cancer Therapy

“…Other biotechnological companies, like OPKO Health, Inc., Miami, FL, USA, Alnylam Pharmaceuticals, Cambridge, MA, USA, Interna Technologies, Utrecht, The Netherlands and Mello Biotech, Santa Fe Springs, CA, USA are in the screening phase [235]. Additionally, Rosetta Genomics, Princeton, NJ, USA [239], RXi Pharmaceuticals, Marlborough, MA, USA [240], Phio Pharmaceuticals, Marlborough, MA, USA [241], Asuragen, Inc., Austin, TX, USA [242], Sirnaomics, Inc., Germantown, TN, USA [243], Bristol-Myers Squibb, New York, NY, USA [244], and Dicerna Pharmaceuticals, Lexington, KY, USA [245] have developed miRNA-based biomarkers. A snapshot of the progress in the biopharmaceutical pipeline that could increase the number of miRNA therapeutics is shown in Table 2.…”

miR-22 negatively regulating NOD-like receptor protein 3 gene in the proliferation, invasion, and migration of malignant melanoma cells

“…As against the physiological state of normal tissues, the expression profile of miRNA in cancer cells shows abnormal changes. Based on the effect of miRNA on its target genes, it has been confirmed that miRNA can inhibit or promote tumour growth [ 8 ]. The increase of oncogenic miRNA is caused by the abnormal amplification and ectopic of miRNA genes.…”