期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms24076825
关键词
uveal melanoma; proteomics; aqueous humor; biomarkers; ocular liquid biopsy; ocular cancer
Gene expression profiling (GEP) has been clinically validated to stratify uveal melanoma (UM) patients based on metastatic risk. However, it requires invasive intraocular tumor biopsy. This study explores the use of ocular liquid biopsy, specifically aqueous humor (AH), to determine the metastatic potential of UM patients based on protein expression analysis. Significant differentially expressed proteins (DEPs) in AH were identified, which can differentiate GEP class 1 and 2 and provide insights into metastasis-related pathways. AH liquid biopsy offers a non-invasive alternative for assessing metastatic risk in UM patients.
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.
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