RNA expression signatures as predictors of prognosis in thin and thick primary cutaneous melanoma.
Abstract
e21602 Background: Risk stratification of primary cutaneous melanoma based on Breslow thickness remains clinically imperfect, particularly in thin tumors (≤1 mm), where a subset progresses unexpectedly. Previously, targeted RT-PCR analyses of established tissue RNA markers demonstrated prognostic utility mainly in thick melanoma, with no robust markers identified for thin tumors, prompting an unbiased RNA sequencing approach to address this gap.Objectives: Identify RNA expression signatures associated with prognosis in thin (≤1 mm) and thick (≥4 mm) primary cutaneous melanoma. Methods: RNA-seq was performed on primary tumor tissue from 51 thin and 65 thick melanomas after hybrid-capture library preparation and deep sequencing (NovaSeq 6000, S4). Expression was quantified for 18,146 genes, including full coding regions of 17,702 protein-coding genes (54,142 transcripts), using a standardized four-step pipeline with stringent filtering. Analyses were performed by clinical outcome (regional recurrence and/or distant metastases and/or death) and to build classifiers distinguishing thin vs thick melanoma. Results: In thin melanoma, 69 genes were differentially expressed by outcome; a 10-marker panel (BAIAP2L1, DMRT3, ENSG00000305404, HOXA11-AS, MGP, MIR1183, MUC6, NBPF17P, NANOS3, TMEM191C) showed the best prognostic performance (AUROC 0.835). In thick melanoma, 26 prognostic genes were identified; a 6-marker panel (EEF1A1P16, HSPA8P5, IBSP, MEX3B, MMP3, VAMP2) achieved AUROC 0.93. A shared 4-marker signature (MMP3, RGS1, SPP1, VAMP2) performed consistently across thin and thick tumors (AUROC 0.80). A 5-marker classifier (ALOX12, COL22A1, KRT10-AS1, S100B, SPP1) distinguished thin vs thick melanomas (AUROC 0.96), supporting distinct transcriptional programs linked to thickness and progression biology. Conclusions: RNA profiling reveals substantial prognostic heterogeneity within thin melanoma and identifies multigene signatures that may refine risk stratification beyond Breslow thickness. Divergent prognostic panels in thin vs thick tumors suggest distinct mechanisms of progression and support development of clinically deployable RNA-based assays for risk-adapted management.These signatures identify biologically aggressive subsets within thin melanoma that may warrant intensified surveillance or consideration of adjuvant strategies.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (15)
Igor V. Samoylenko
FSBI "National Medical Research Oncology Center named after N.N. Blokhin " of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
Andrew R. Zaretsky
Department of Molecular Technologies Research Institute of Translational Medicine N. I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
Kristina V. Orlova
FSBI "National Medical Research Oncology Center named after N.N. Blokhin " of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
Oleg V. Drozd
Department of Molecular Technologies Research Institute of Translational Medicine N. I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
Irina N. Mikhaylova
Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation
Nina Vand
Department of Molecular Technologies Research Institute of Translational Medicine N. I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
Viktoriya Prokopenko
Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation
Ilya A. Dyugay
Department of Molecular Technologies Research Institute of Translational Medicine N. I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
Yana V. Vishnevskaya
Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation
Alexandra M. Bershchanskaya
Department of Molecular Technologies Research Institute of Translational Medicine N. I. Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation
Sergey A. Yargunin
State Budgetary Healthcare Organisation “Clinical Oncology Dispensary No.1” under the Ministry of Healthcare of Krasnodar region (SBHI COD No. 1), Krasnodar, Russian Federation
Anna Artemyeva
Federal State Budget Institution "National Medical Research Center of Oncology named after N.N. Petrov" Ministry of Healthcare of Russian Federation, Saint Petersburg, Russian Federation
Kirill A. Baryshnikov
Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation
Galina Kharkevich
Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation
Lev V. Demidov
FSBI "National Medical Research Oncology Center named after N.N. Blokhin " of the Ministry of Health of the Russian Federation, Moscow, Russian Federation