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ArticleInvestigative ophthalmology & visual science2026

Comparative Proteomic Profiling of Microdissected Spindle and Epithelioid Uveal Melanoma Subtypes.

Yu Luan, Jieling Tang, Tianyu Zhu, Xiang Gu, Yihang Chen, Pengsen Wu, Xianting Ding, Ludi Yang, Lin Ye, Wenyue Zhang and 4 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

14 authors.

Yu LuanState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jieling TangState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tianyu ZhuState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiang GuState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yihang ChenState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Pengsen WuShenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, China.
Xianting DingDepartment of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Ludi YangState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Lin YeShenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, Shenzhen, China.
Wenyue ZhangState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ai ZhuangState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Renbing JiaState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peiwei ChaiState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xianqun FanState Key Laboratory of Eye Health, Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Uveal melanoma (UM), the most prevalent primary intraocular cancer in adults, is defined by salient histopathological diversity. Spindle and epithelioid cells constitute its two dominant pathological lineages, yet the latter foreshadows aggressive behavior and shortened survival. This study aimed to explore the molecular and metabolic underpinnings of UM pathology using regionally resolved proteomics. Methods: Formalin-fixed, paraffin-embedded tumors from four patients-two spindle cell and two epithelioid-were histologically stratified via hematoxylin and eosin staining and subsequently interrogated by regionally resolved proteomics across eight precisely mapped regions. Immunofluorescence corroborated the shifts in melanocyte lineage markers. To translate these tissue-level signatures into functional biology, spindle-like 92.1 and epithelioid Mel290 cell lines were subjected to quantitative RT-PCR and Seahorse metabolic profiling, quantifying oxidative-phosphorylation (OXPHOS) gene expression and mitochondrial respiration. Results: Proteomic profiling of microdissected tissue uncovered a selective collapse of the melanocytic differentiation program within epithelioid foci. Endothelin receptor type B, the receptor required for melanocyte stem cell fate, and the lineage-defining calcium-binding protein S100B were both sharply repressed in epithelioid samples, with S100B registering the single largest drop across the entire dataset. Immunofluorescence corroborated this signature, revealing concomitant loss of microphthalmia-associated transcription factor and premelanosome protein, further attesting to the dedifferentiated state of epithelioid cells. Simultaneously, the same regions exhibited a striking surge in OXPHOS machinery. Concordantly, Mel290 epithelioid cells displayed elevated transcription of OXPHOS genes and a markedly higher basal and maximal oxygen consumption rate compared with the spindle-like 92.1 line, aligning tissue-level proteomic shifts with cell-autonomous metabolic rewiring. Conclusions: Our findings reveal a distinct proteomic signature in epithelioid UM characterized by dedifferentiation and enhanced mitochondrial respiration. This study provides the first regionally resolved proteomic landscape of UM pathology and suggests that the epithelioid transformation may reflect a shift toward a dedifferentiated, metabolically active tumor state.

Indexed as

Epithelioid CellsMelanomaProteomicsUveal NeoplasmsBiomarkers, TumorCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMicrodissectionOxidative PhosphorylationUveal MelanomaBiomarkers, Tumor

Identifiers

PMID41983767
PMCPMC13094782

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.