Article
Biochemistry & Molecular Biology
Chen-Ching Peng, Shreya Sirivolu, Sarah Pike, Mary E. Kim, Bibiana Reiser, Hong-Tao Li, Gangning Liang, Liya Xu, Jesse L. Berry
Summary: 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.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Prisca Bustamante, Leo Piquet, Solange Landreville, Julia Burnier
Summary: Uveal melanoma is an intraocular tumor that tends to metastasize to the liver. Despite identifying early driver mutations, the process of UM metastasis remains incompletely understood. A better understanding of genetic, molecular, and environmental factors could lead to new approaches for UM treatment.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Oncology
Patrick Demkowicz, Renelle Pointdujour-Lim, Sofia Miguez, Yesung Lee, Bailey S. C. L. Jones, Christopher A. Barker, Marcus Bosenberg, David H. Abramson, Alexander N. Shoushtari, Harriet Kluger, Jasmine H. Francis, Mario Sznol, Mathieu F. Bakhoum
Summary: This study retrospectively analyzed clinical data of patients with metastatic uveal melanoma and found that female sex, treatment with immune checkpoint inhibitors, and the absence of liver metastasis were associated with better survival outcomes. These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma.
Article
Multidisciplinary Sciences
Zhe Zhang, Chen Li, Qian Li, Xiaoming Su, Jiayi Li, Lili Zhu, Xinhua (James) Lin, Jianfeng Shen
Summary: Alternative splicing is an important mechanism for protein diversity, but our understanding of protein structures has been limited. However, the release of AlphaFold has allowed for the prediction of protein structures, enabling the exploration of abnormal isoforms in uveal melanoma patients. This dataset provides valuable structural information for studying potential therapeutic targets and cancer neoantigens at an atomic level.
Article
Oncology
Han Yue, Binbin Xu, Jian Gao, Yingwen Bi, Kang Xue, Jie Guo, Rui Zhang, Hui Ren, Yifei Yuan, Jiang Qian
Summary: A simple and widely applicable prognostic prediction model for uveal melanoma (UM) in a Chinese population was established. The model, based on five relevant variables, showed superior prediction compared to traditional staging systems. The model also demonstrated good accuracy and stability in external validation cohorts.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Shirly Grynberg, Ronen Stoff, Nethanel Asher, Ronnie Shapira-Frommer, Jacob Schachter, Ory Haisraely, Yaacov Lawrence, Guy Ben-Betzalel
Summary: The study suggests that the combination therapy of radiotherapy and immunotherapy may significantly improve overall response rate and survival time in patients with metastatic uveal melanoma. Further prospective studies with larger sample sizes are warranted.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2022)
Article
Cell Biology
Bo Liu, Xueting Yao, Chaoyang Zhang, Yufen Liu, Li Wei, Qinying Huang, Mengting Wang, Yanchen Zhang, Danning Hu, Wencan Wu
Summary: Autophagy dysfunction is a common cause of tumor formation and plays a crucial role in uveal melanoma (UM). This study reveals that PTK6 inhibits autophagy to promote the proliferation, migration, and invasion of UM cells. In contrast, SOCS3 inhibits the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 partially reverses the PTK6-induced promotion of UM cell proliferation, migration, and invasion.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Alexej Ballhausen, Elizabeth Urias, Stephen K. Gruschkus, Michelle Williams, Maura S. Glover, Yong Qin, Dan S. Gombos, Sapna P. Patel
Summary: The study found that in uveal melanoma Class 1A patients, those with stage III disease and/or large COMS size are at elevated risk for metastasis. Combined clinical decision-making using AJCC stage and COMS size can have a significant impact on improving risk stratification and adapting follow-up intervals for Class 1A UM patients.
Article
Biochemistry & Molecular Biology
Daniel P. de Bruyn, Michiel Bongaerts, Ramon Bonte, Jolanda Vaarwater, Magda A. Meester-Smoor, Robert M. Verdijk, Dion Paridaens, Nicole C. Naus, Annelies de Klein, George J. G. Ruijter, Emine Kilic, Erwin Brosens
Summary: Using untargeted metabolomics, we identified differential metabolite patterns in UM patients compared to controls. The random forest classifier and leave-one-out cross-validation confirmed the discriminatory ability of these metabolite patterns in distinguishing UM patients from controls, but not in differentiating high-risk and low-risk UM patients. Dysregulation of metabolite patterns may be associated with processes related to malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Alexander Z. Wei, Matan Uriel, Agata Porcu, Michael P. Manos, Ann C. Mercurio, Michael M. Caplan, Liam Hulse, Rino S. Seedor, Marta Holovatska, Jasmine Francis, Shaheer A. Khan, Diana E. McDonnell, Dmitry Bogomolny, Takami Sato, Brian P. Marr, Rizwan Haq, Marlana Orloff, Alexander Shoushtari, Richard D. Carvajal
Summary: This study retrospectively analyzed data from 1,845 mUM patients and found that the incidence of brain metastases (BM) was 6.3%. BM was associated with high disease burden and a median survival of under 8 months. Routine brain imaging is suggested for early detection of BM in mUM patients at risk.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Han, Timothy J. Purwin, Nelisa Bechtel, Connie Liao, Vivian Chua, Erin Seifert, Takami Sato, Zachary T. Schug, David W. Speicher, J. William Harbour, Andrew E. Aplin
Summary: Cancer cell metabolism in BAP1 mutant uveal melanoma shows heterogeneity with distinct usage of metabolic pathways. Targeting cancer metabolism could be a promising therapeutic option, but tailored approaches are needed due to metabolic heterogeneities in BAP1 mutant UM. Overall, understanding metabolic diversity is crucial for developing effective treatment strategies.
Article
Pharmacology & Pharmacy
Bei Jin, Luo Yang, Qianyun Ye, Jingxuan Pan
Summary: Hepatic metastasis is a common and poorly treated cause of death in uveal melanoma (UM) patients. The mechanism underlying liver metastasis remains unknown. This study suggests that decapping scavenger enzymes (DCPS) impact ferroptosis by regulating mRNA decay during the metastatic colonization of UM cells to liver. Inhibition of DCPS induces gene transcript alteration and ferroptosis by reducing the mRNA turnover of GLRX. Inhibition of DCPS also eliminates cancer stem-like cells in UM and hampers the growth and proliferation of UM cells both in vitro and in vivo. Additionally, targeting DCPS diminishes hepatic metastasis of UM cells, providing a potential target for metastatic colonization in UM.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Viera Horvathova Kajabova, Andrea Soltysova, Lucia Demkova, Paulina Plesnikova, Darina Lyskova, Alena Furdova, Pavel Babal, Bozena Smolkova
Summary: Our study found that KIT positivity was associated with a more than 17-fold increase in the risk of poor prognosis in uveal melanoma, and a strong negative correlation was identified between mRNA expression and DNA methylation values for 12 of 20 analyzed positions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Mathilde Saint-Ghislain, Anne-Celine Derrien, Lionnel Geoffrois, Lauris Gastaud, Thierry Lesimple, Sylvie Negrier, Nicolas Penel, Jean-Emmanuel Kurtz, Yannick Le Corre, Caroline Dutriaux, Sophie Gardrat, Raymond Barnhill, Alexandre Matet, Nathalie Cassoux, Alexandre Houy, Toulsie Ramtohul, Vincent Servois, Pascale Mariani, Sophie Piperno-Neumann, Marc-Henri Stern, Manuel Rodrigues
Summary: In patients with metastatic uveal melanomas, MBD4 mutations are associated with response to immune checkpoint inhibitors, progression-free survival, and overall survival benefits. MBD4 could serve as a predictive biomarker for the efficacy of ICI treatment.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Ophthalmology
Deep Sarode, Tara McClay, Fiona Roberts, Julie Connolly, Paul Cauchi, Vikas Chadha
Summary: This study investigated the outcomes of patients with uveal melanoma (UM) who underwent enucleation at a tertiary referral center in Scotland, and assessed the effect of extrascleral extension (ESE) on these outcomes. The presence of ESE was associated with a significantly shorter length of survival, particularly in cases with ESE > 5 mm or high-risk characteristics warranting adjuvant external beam radiotherapy (EBRT).
