Diagnostic Aqueous Humor Proteome Predicts Metastatic Potential in Uveal Melanoma.

Diagnostic Aqueous Humor Proteome Predicts Metastatic Potential in Uveal Melanoma.
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DOI:
10.3390/ijms24076825
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发表时间:
2023-04-06
影响因子:
5.6
通讯作者:
Berry, Jesse L.
Berry, Jesse L.
中科院分区:
生物学2区
文献类型:
--
作者:
Peng, Chen-Ching;Sirivolu, Shreya;Pike, Sarah;Kim, Mary E.;Reiser, Bibiana;Li, Hong-Tao;Liang, Gangning;Xu, Liya;Berry, Jesse L.

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基因表达谱 (GEP) 经过临床验证,可将葡萄膜黑色素瘤 (UM) 患者分为两个高度预后的分子类别:1 类(低转移风险)和 2 类(高转移风险),从而对转移风险进行分层。但GEP需要眼内肿瘤活检,受到肿瘤体积小和肿瘤异质性的限制;此外,视网膜出血、出血或肿瘤扩散的风险也很小。因此,眼部液体活检已成为一种侵入性较小的替代方案。在这项研究中,我们试图使用诊断性 AH 液体活检标本来确定与高级 GEP 2 类相关的房水 (AH) 蛋白质组。从 UM 患者中收集了 20 个 AH 样本,并按 GEP 类别分组。分析了 1472 个目标的蛋白质表达水平,在 GEP 类别之间进行比较,并与临床特征相关。对显着差异表达蛋白(DEP)进行细胞通路分析和上游调节因子鉴定。结果表明,AH 中检测到的 45 个 DEP 可以在诊断时区分 GEP 1 类和 2 类。 IL1R 和 SPRY2 是 8/45 DEP 的潜在上游调节因子,有助于转移相关途径。 AH 液体活检提供了在没有肿瘤活检的情况下确定患者转移潜力的新机会。
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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