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葡萄膜黑色素瘤中表达升高预示患者预后不良。

Elevated Expression in Uveal Melanoma Predicts Poor Patient Prognosis.

作者信息

Yamashita Shin-Nosuke, Tanaka Yoshiatsu, Islam Shajedul, Kotake Honoka, Tanaka Maki, Kitagawa Takao, Tokuda Kazuhiro, Paudel Durga, Giri Sarita, Ohta Tohru, Harada Fumiya, Nagayasu Hiroki, Kuramitsu Yasuhiro

机构信息

Advanced Research Promotion Centre, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, U.S.A.

出版信息

Cancer Genomics Proteomics. 2025 Jun 26;22(4):624-631. doi: 10.21873/cgp.20526.

Abstract

BACKGROUND/AIM: Uveal melanoma (UVM) is the most prevalent primary intraocular malignancy, accounting for 3-5% of all melanomas. Despite its rarity, particularly in Japan (~2 cases per 100,000 individuals annually), UVM exhibits highly aggressive behavior, with nearly 50% of patients developing distant metastases. Once metastasized, the prognosis remains dismal, with a median survival of only 4-5 months. Identifying prognostic biomarkers and potential therapeutic targets is imperative to improve clinical outcomes. Stanniocalcin-1 (STC-1) is a glycoprotein hormone implicated in calcium and phosphate homeostasis. Recent studies have linked overexpression to tumor progression, poor prognosis, and increased metastatic potential in various malignancies. However, the prognostic significance and mechanistic role of STC-1 in UVM remain unexplored.

MATERIALS AND METHODS

To elucidate the clinical relevance of in UVM, we analyzed publicly available transcriptomic datasets using GEPIA2 and UALCAN, assessing mRNA expression across disease stages and its correlation with patient survival. In parallel, single-cell RNA sequencing (scRNA-seq) datasets were utilized to identify the cellular sources of within the UVM tumor microenvironment and to investigate its association with specific functional cellular states.

RESULTS

expression was significantly up-regulated in stage IV UVM tumors compared to stage III (=4 and 36, respectively). Moreover, elevated expression was inversely correlated with overall survival, suggesting its potential role in disease progression. scRNA-seq analysis revealed that is expressed by both tumor cells and fibroblasts, indicating a possible cooperative mechanism that may drive tumor progression.

CONCLUSION

These findings suggest that serves as a potential prognostic biomarker in UVM, providing novel insights into its role in tumor biology. Further investigation is warranted to explore its therapeutic implications and mechanistic contributions to UVM progression.

摘要

背景/目的:葡萄膜黑色素瘤(UVM)是最常见的原发性眼内恶性肿瘤,占所有黑色素瘤的3%至5%。尽管其发病率较低,尤其是在日本(每年每10万人中约有2例),但UVM具有高度侵袭性,近50%的患者会发生远处转移。一旦发生转移,预后仍然很差,中位生存期仅为4至5个月。确定预后生物标志物和潜在治疗靶点对于改善临床结果至关重要。骨钙素-1(STC-1)是一种糖蛋白激素,与钙和磷的体内平衡有关。最近的研究表明,在各种恶性肿瘤中,其过表达与肿瘤进展、预后不良和转移潜能增加有关。然而,STC-1在UVM中的预后意义和机制作用仍未得到探索。

材料与方法

为了阐明STC-1在UVM中的临床相关性,我们使用GEPIA2和UALCAN分析了公开可用的转录组数据集,评估了疾病各阶段的STC-1 mRNA表达及其与患者生存的相关性。同时,利用单细胞RNA测序(scRNA-seq)数据集确定UVM肿瘤微环境中STC-1的细胞来源,并研究其与特定功能细胞状态的关联。

结果

与III期(分别为4例和36例)相比,IV期UVM肿瘤中STC-1的表达显著上调。此外,STC-1表达升高与总生存期呈负相关,表明其在疾病进展中可能发挥作用。scRNA-seq分析显示,肿瘤细胞和成纤维细胞均表达STC-1,这表明可能存在一种协同机制驱动肿瘤进展。

结论

这些发现表明,STC-1可作为UVM的潜在预后生物标志物,为其在肿瘤生物学中的作用提供了新的见解。有必要进一步研究以探索其治疗意义及其对UVM进展的机制贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f26f/12216570/e05e24e72207/cgp-22-627-g0001.jpg

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