QS20. The melanocytic transcriptomic state is independently associated with poor overall survival in long term follow up of patients with metastatic melanoma

Thursday, March 5, 2026

3:37 PM - 3:41 PM MST

Location: Immuno-Oncology HUB Zone

Co-Author(s)

ZH

Ziyin Huang, BS

Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan
Ann Arbor, Michigan, United States
Kristen E. Rhodin, MD, MHS

General Surgery Resident
Department of Surgery, Duke University, Durham, NC
Durham, North Carolina, United States
RA

Ranu Al-Rohil, MD, PhD

Department of Dermatology, University North Carolina, Chapel Hill, NC
Chapel Hill, North Carolina, United States
AC

Arul Chinnaiyan, MD, PhD

Department of Computational Medicine and Bioinformatics; Department of Urology, University of Michigan, Ann Arbor, Michigan
Ann Arbor, Michigan, United States
MO

Margaret O'Connor, MD, PhD

General Surgery Resident
Duke University
Durham, North Carolina, United States
Christina V. Angeles, MD, FACS (she/her/hers)

Surgical Oncologist
University of Michigan
Ann Arbor, Michigan, United States
SN

Smita Nair, PhD

Professor of Surgery
Department of Surgery, Duke University, Durham, NC
Durham, North Carolina, United States
GB

Georgia M. Beasley, MD, MHSc, FACS (she/her/hers)

Associate Professor of Surgery with tenure
Duke University
Durham, North Carolina, United States
MI

Matthew Iyer, MD, PhD

Assistant Professor
Department of Surgery, University of Michigan, Ann Arbor, MI.
Ann Arbor, Michigan, United States

Primary Presenter(s)

Isabel DeLaura, MD (she/her/hers)

Resident
Duke University Hospital
Durham, North Carolina, United States

Slides

Introduction: Melanomas display distinct transcriptomic states, but it remains unclear how they associate with clinical outcomes. We performed digital spatial RNA profiling (DSP-RNA) of metastatic tumors from patients to investigate how transcriptomic states correlate with OS and acral melanoma (AM) status.

Methods: We performed DSP-RNA across a tissue microarray constructed from 111 patients with in-transit metastatic melanoma (ITM) diagnosed from 1990-2020. Data quality control, noise correction, and normalization yielded high quality profiles from 105 patients, including 30 (36%) who received immune checkpoint inhibitors, and 20 (24%) with AM.

Results: We performed principal component analysis (PCA) and correlated the results with published gene signatures: the PC1 axis differentiated transitory from undifferentiated melanoma, PC2 reflected immune cell infiltration, PC3 corresponded to stromal cells and neural crest-like melanoma, and PC4 associated with melanocytic melanoma. Across a cohort of treatment-naïve ITM, high expression of the melanocytic state conferred a median overall survival difference of 7.59 years (melanocytic ‘high’=5.16 years vs ‘low’=12.75 years, log-rank p=0.0024) and independently associated with poor survival in multivariate analysis. AMs showed higher melanocytic state gene expression compared to non-acral cases. These findings were validated in external datasets, supporting that the melanocytic state predicts poor prognosis.

Conclusions: The melanocytic state is associated with poor prognosis and may be enriched in AM, implying that identifying patients with melanocytic melanoma may be important for therapeutic decisions. Unlike other gene expression predictors proposed for prognostic stratification, the melanocytic state characterizes a biological subtype, suggesting that it may have specific therapeutic vulnerabilities.

Learning Objectives:

Melanocytic state may be enriched in acral melanoma and is associated with poor prognosis.
The melanocytic state characterizes a biological subtype and therefore may have important implications for therapeutic decision making.