Diagnostic Aqueous Humor Proteome Predicts Metastatic Potential in Uveal Melanoma

Gene expression profiling (GEP) is clinically validated to stratify the risk of metastasis by assigning uveal melanoma (UM) patients to two highly prognostic molecular classes: class 1 (low metastatic risk) and class 2 (high metastatic risk). However, GEP requires intraocular tumor biopsy, which is...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-04, Vol.24 (7), p.6825
Main Authors: Peng, Chen-Ching, Sirivolu, Shreya, Pike, Sarah, Kim, Mary E, Reiser, Bibiana, Li, Hong-Tao, Liang, Gangning, Xu, Liya, Berry, Jesse L
Format: Article
Language:English
Subjects:
Analysis
Aqueous Humor - metabolism
Aqueous humour
Biomarkers
Biopsy
Biopsy, Fine-Needle
Diagnosis
Diagnostic systems
Gene expression
Hemorrhage
Heterogeneity
Humans
Interleukin 1 receptors
Intracellular Signaling Peptides and Proteins
Medical prognosis
Melanoma
Membrane Proteins
Metastases
Metastasis
Mutation
Patients
Protein expression
Proteins
Proteome
Proteomes
Proteomics
Risk
Surveillance
Tumors
Uveal Neoplasms - genetics
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Summary:Gene expression profiling (GEP) is clinically validated to stratify the risk of metastasis by assigning uveal melanoma (UM) patients to two highly prognostic molecular classes: class 1 (low metastatic risk) and class 2 (high metastatic risk). However, GEP requires intraocular tumor biopsy, which is limited by small tumor size and tumor heterogeneity; furthermore, there are small risks of retinal hemorrhage, bleeding, or tumor dissemination. Thus, ocular liquid biopsy has emerged as a less-invasive alternative. In this study, we seek to determine the aqueous humor (AH) proteome related to the advanced GEP class 2 using diagnostic AH liquid biopsy specimens. Twenty AH samples were collected from patients with UM, grouped by GEP classes. Protein expression levels of 1472 targets were analyzed, compared between GEP classes, and correlated with clinical features. Significant differentially expressed proteins (DEPs) were subjected to analysis for cellular pathway and upstream regulator identification. The results showed that 45 DEPs detected in the AH could differentiate GEP class 1 and 2 at diagnosis. IL1R and SPRY2 are potential upstream regulators for the 8/45 DEPs that contribute to metastasis-related pathways. AH liquid biopsy offers a new opportunity to determine metastatic potential for patients in the absence of tumor biopsy.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24076825