Identification of a novel immune-related gene signature for prognosis and the tumor microenvironment in patients with uveal melanoma combining single-cell and bulk sequencing data

Wanpeng Wang; Han Zhao; Sha Wang

doi:10.3389/fimmu.2023.1099071

Identification of a novel immune-related gene signature for prognosis and the tumor microenvironment in patients with uveal melanoma combining single-cell and bulk sequencing data

Front Immunol. 2023 Jan 30:14:1099071. doi: 10.3389/fimmu.2023.1099071. eCollection 2023.

Authors

Wanpeng Wang^{1

2

3}, Han Zhao⁴, Sha Wang^{1

2

3}

Affiliations

¹ Eye Center of Xiangya Hospital, Central South University, Changsha, China.
² Hunan Key Laboratory of Ophthalmology, Hunan, Changsha, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
⁴ Department of Ophthalmology, Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.

Abstract

Introduction: Uveal melanoma (UVM) is the most invasive intraocular malignancy in adults with a poor prognosis. Growing evidence revealed that immune-related gene is related to tumorigenesis and prognosis. This study aimed to construct an immune-related prognostic signature for UVM and clarify the molecular and immune classification.

Methods: Based on The Cancer Genome Atlas (TCGA) database, single-sample gene set enrichment (ssGSEA) and hierarchical clustering analysis were performed to identify the immune infiltration pattern of UVM and classify patients into two immunity clusters. Then, we proposed univariate and multivariate Cox regression analysis to identify immune-related genes that related to overall survival (OS) and validated in the Gene Expression Omnibus (GEO) external validation cohort. The molecular and immune classification in the immune-related gene prognostic signature defined subgroups were analyzed.

Results: The immune-related gene prognostic signature was constructed based on S100A13, MMP9, and SEMA3B genes. The prognostic value of this risk model was validated in three bulk RNA sequencing datasets and one single-cell sequencing dataset. Patients in the low-risk group had better OS than those in the high-risk group. The receiver-operating characteristic (ROC) analysis revealed its strong predictive ability for UVM patients. Lower expression of immune checkpoint genes was presented in the low-risk group. Functional studies showed that S100A13 knockdown via siRNA inhibited UVM cell proliferation, migration, and invasion in vitro, with the increased expression of reactive oxygen species (ROS) related markers in UVM cell lines.

Discussion: The immune-related gene prognostic signature is an independent predictive factor for the survival of patients with UVM and provides new information about cancer immunotherapy in UVM.

Keywords: immune checkpoint; immune-related gene; prognostic signature; tumor microenvironment; uveal melanoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Humans
Melanoma* / genetics
Prognosis
Tumor Microenvironment / genetics
Uveal Neoplasms* / genetics

Supplementary concepts

Uveal melanoma

Grants and funding

This research was funded by grants from Natural Science Foundation of Hunan Provincial (2020JJ4912, 2022JJ30964).