American Association for Cancer Research
10780432ccr142566-sup-138779_2_supp_2998731_np2x80.png (61.49 kB)

Supplementary Figure S1 from A miRNA-Based Signature Detected in Primary Melanoma Tissue Predicts Development of Brain Metastasis

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posted on 2023-03-31, 18:41 authored by Doug Hanniford, Judy Zhong, Lisa Koetz, Avital Gaziel-Sovran, Daniel J. Lackaye, Shulian Shang, Anna Pavlick, Richard Shapiro, Russell Berman, Farbod Darvishian, Yongzhao Shao, Iman Osman, Eva Hernando

Supplementary Figure S1. This figure depicts in waterfall plots the individual patient risk scores derived from the miRNA signature + stage prognostic model.



Purpose: Brain metastasis is the major cause of mortality among patients with melanoma. A molecular prognostic test that can reliably stratify patients at initial melanoma diagnosis by risk of developing brain metastasis may inform the clinical management of these patients.Experimental Design: We performed a retrospective, cohort-based study analyzing genome-wide and targeted microRNA expression profiling of primary melanoma tumors of three patient cohorts (n = 92, 119, and 45) with extensive clinical follow-up. We used Cox regression analysis to establish a microRNA-based signature that improves the ability of the current clinicopathologic staging system to predict the development of brain metastasis.Results: Our analyses identified a 4-microRNA (miR-150-5p, miR-15b-5p, miR-16-5p, and miR-374b-3p) prognostic signature that, in combination with stage, distinguished primary melanomas that metastasized to the brain from nonrecurrent and non–brain metastatic primary tumors (training cohort: C-index = 81.4%, validation cohort: C-index = 67.4%, independent cohort: C-index = 76.9%). Corresponding Kaplan–Meier curves of high- versus low-risk patients displayed a clear separation in brain metastasis-free and overall survival (training: P < 0.001; P < 0.001, validation: P = 0.033; P = 0.007, independent: P = 0.021; P = 0.022, respectively). Finally, of the microRNA in the prognostic model, we found that the expression of a key lymphocyte miRNA, miR-150-5p, which is less abundant in primary melanomas metastatic to brain, correlated with presence of CD45+ tumor-infiltrating lymphocytes.Conclusions: A prognostic assay based on the described miRNA expression signature combined with the currently used staging criteria may improve accuracy of primary melanoma patient prognoses and aid clinical management of patients, including selection for adjuvant treatment or clinical trials of adjuvant therapies. Clin Cancer Res; 21(21); 4903–12. ©2015 AACR.