# Project 3: Prognostic and Functional Role of a Gene Expression Signature in Melanoma Patients

> **NIH NIH P01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $342,005

## Abstract

PROJECT SUMMARY 
 Despite recent therapeutic advances, metastatic melanoma remains a disease with poor prognosis. 
Patients with primary melanomas that are clinically and histologically similar at the time of initial diagnosis often 
have vastly different outcomes, from patients who are cured after initial surgical resection to those that develop 
recurrence(s), metastatic progression, and eventually die. Such highly variable outcomes suggest underlying 
biological differences in patient tumors (cell-intrinsic) or the patients themselves (cell-extrinsic, e.g. immune 
response). Recent studies suggest that early tumorigenic events can reflect a melanoma's potential to spread. 
Conceptually, if such molecular alterations can be robustly measured at the time of melanoma diagnosis, they 
may be useful prognostic markers. Moreover, some of these markers may also be functional drivers of disease 
progression, thus their study may yield novel insights into melanoma biology and new therapeutic targets. 
 We hypothesize that altered gene expression can predict patient outcome and, moreover, that some 
prognostic biomarkers are functional drivers of melanoma progression. Our group and others have observed 
that expression of various mRNA and microRNA (miRNA) may have prognostic value for patients with primary 
melanoma. We propose to examine the expression of a panel of ~230 mRNA/miRNA previously associated to 
poor outcomes in melanoma in a multi-institutional cohort of primary melanoma patients (n = 1000, stages IIA- 
IIIB at diagnosis) with extensive clinical follow-up. Using this expression data, we propose to develop and 
validate a refined tissue-based, molecular prognostic mRNA/miRNA signature for stages IIA to IIIB melanomas 
(Aims 1 and 2). In addition, we will investigate if candidate prognostic genes (as defined by each of the P01 
projects) can be functional mediators of the aggressive phenotype. We propose to perform in vivo pooled 
library-based functional screens to examine the effects of modulation of candidate prognostic genes on tumor 
growth and metastatic potential of melanoma cells (Aim 3.1). Moreover, we will investigate cellular properties 
underlying the effects of functionally relevant candidate genes identified in in vivo screens (Aim 3.2). 
 A molecular signature that, at initial diagnosis, can reliably predict outcomes for primary melanoma patients 
could transform clinical management of these individuals, informing selection of higher-risk patients for 
increased surveillance and/or adjuvant therapy. The hope is that better melanoma patient management will 
lead to improved outcomes, such as prolonging patient survival or reducing morbidity and mortality. In addition, 
the described functional studies will reveal candidate genes (from all projects of the P01) that contribute to 
melanoma progression and metastasis, which might open new therapeutic avenues against this devastating 
disease. 
!

## Key facts

- **NIH application ID:** 10188451
- **Project number:** 5P01CA206980-05
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Eva Hernando
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $342,005
- **Award type:** 5
- **Project period:** 2017-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188451

## Citation

> US National Institutes of Health, RePORTER application 10188451, Project 3: Prognostic and Functional Role of a Gene Expression Signature in Melanoma Patients (5P01CA206980-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10188451. Licensed CC0.

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