Research Paper Volume 12, Issue 20 pp 20254—20267
Development and validation of an immune and stromal prognostic signature in uveal melanoma to guide clinical therapy
- 1 School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
- 2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
Received: March 17, 2020 Accepted: July 14, 2020 Published: October 26, 2020
https://doi.org/10.18632/aging.103779How to Cite
Copyright: © 2020 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The tumor microenvironment is known to play an important role in uveal melanoma. Reliable prognostic signatures are needed to aid high risk patients and improve prognosis. Uveal melanoma tissues from three public datasets were analyzed. RNA sequence data of uveal melanoma and corresponding clinical features were obtained from The Cancer Genome Atlas database. Immune and stromal scores were calculated by applying the “ESTIMATE” algorithm. The samples were divided into high and low immune or stromal score groups. We constructed prognostic models by using the ‘lasso’ package and tested them for 500 iterations. The cell signature was validated in another GSE44295 and GSE84976 datasets. We found that the median survival time of the low immune/stromal score group is longer than that of the high-score group. Thirteen immune cells and one stromal cell were concerned significant in predicting poor overall survival rate. Finally, a four-cell model was identified. Further validation revealed that the low-risk group has a significantly better survival than the high-risk group in another two datasets (P < 0.05). Moreover, the high-risk group is more sensitive to immunotherapy and chemotherapy. Summarizing, the proposed immune cells signature is a promising biomarker for estimating overall survival in uveal melanoma.
Abbreviations
AUC: area under the curve; BAP1: BRCA1-associated protein-1; CI: confidence interval; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; EMC: epithelial-to-mesenchymal transition; ESTIMATE: Estimation of STromal and Immune cells in MAlignant Tumor tissue using Expression data; FGF: fibroblast growth factor; GDSC: Genomics of Drug Sensitivity in Cancer; GSVA: gene set variation analysis; HR: hazard ratio; IC50: half maximal inhibitory concentration; OR: odds ratio; PD-L1: programmed death-ligand 1; RNA: ribonucleic acid; TCGA: The Cancer Genome Atlas.