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

被引:3
|
作者
Kobeissi, Iyad [1 ]
Eljilany, Islam [1 ]
Achkar, Tala [2 ]
LaFramboise, William A. [3 ]
Santana-Santos, Lucas [4 ]
Tarhini, Ahmad A. [1 ,5 ]
机构
[1] H Lee Moffitt Canc Ctr & Res Inst, Cutaneous Oncol & Immunol Dept, Tampa, FL 33612 USA
[2] Univ Pittsburgh, Med Ctr, Hematol Dept, Pittsburgh, PA 15213 USA
[3] Allegheny Hlth Network, Allegheny Canc Inst, Pathol & Lab Med Dept, Pittsburgh, PA 15524 USA
[4] Northwestern Univ, Feinberg Sch Med, Pathol Dept, Chicago, IL 60611 USA
[5] Univ S Florida, Morsani Coll Med, Oncol Sci Dept, Tampa, FL 33602 USA
基金
美国国家卫生研究院;
关键词
biomarkers; immunotherapy; melanoma; miRNA; microRNA; CANCER; PROGRESSION; METASTASIS; INTERGROUP; INVASION; CELLS; TRIAL;
D O I
10.3390/ijms24098167
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x 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.
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页数:11
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