Elevated VEGF-A &amp; PLGF concentration in aqueous humor of patients with uveal melanoma following Iodine-125 plaque radiotherapy

Chen, Mengxi; Liu, Yueming; Li, Yang; Yang, Xuan; Wei, Wenbin

doi:10.18240/ijo.2020.04.11

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…This observation is supported by the finding that cytokine expression patterns in the AH discriminated between high- and low-risk UM patients [ 48 ]. During plaque brachytherapy implantation in UM patients, an anterior chamber paracentesis is a feasible and safe procedure that can be performed [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating tumor DNA tracking through driver mutations as a liquid biopsy-based biomarker for uveal melanoma

Bustamante

Tsering

Coblentz

et al. 2021

J Exp Clin Cancer Res

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Background Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite good primary tumor control, up to 50% of patients develop metastasis, which is lethal. UM often presents asymptomatically and is usually diagnosed by clinical examination and imaging, making it one of the few cancer types diagnosed without a biopsy. Hence, alternative diagnostic tools are needed. Circulating tumor DNA (ctDNA) has shown potential as a liquid biopsy target for cancer screening and monitoring. The aim of this study was to evaluate the feasibility and clinical utility of ctDNA detection in UM using specific UM gene mutations. Methods We used the highly sensitive digital droplet PCR (ddPCR) assay to quantify UM driver mutations (GNAQ, GNA11, PLCβ4 and CYSTLR2) in cell-free DNA (cfDNA). cfDNA was analyzed in six well established human UM cell lines with known mutational status. cfDNA was analyzed in the blood and aqueous humor of an UM rabbit model and in the blood of patients. Rabbits were inoculated with human UM cells into the suprachoroidal space, and mutated ctDNA was quantified from longitudinal peripheral blood and aqueous humor draws. Blood clinical specimens were obtained from primary UM patients (n = 14), patients presenting with choroidal nevi (n = 16) and healthy individuals (n = 15). Results The in vitro model validated the specificity and accuracy of ddPCR to detect mutated cfDNA from UM cell supernatant. In the rabbit model, plasma and aqueous humor levels of ctDNA correlated with tumor growth. Notably, the detection of ctDNA preceded clinical detection of the intraocular tumor. In human specimens, while we did not detect any trace of ctDNA in healthy controls, we detected ctDNA in all UM patients. We observed that UM patients had significantly higher levels of ctDNA than patients with nevi, with a strong correlation between ctDNA levels and malignancy. Noteworthy, in patients with nevi, the levels of ctDNA highly correlated with the presence of clinical risk factors. Conclusions We report, for the first time, compelling evidence from in vitro assays, and in vivo animal model and clinical specimens for the potential of mutated ctDNA as a biomarker of UM progression. These findings pave the way towards the implementation of a liquid biopsy to detect and monitor UM tumors.

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Section: Discussionmentioning

confidence: 99%

Circulating tumor DNA tracking through driver mutations as a liquid biopsy-based biomarker for uveal melanoma

Bustamante

Tsering

Coblentz

et al. 2021

J Exp Clin Cancer Res

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“…The elevated vitreous levels of VEGF may play an important role in UM genesis and radiotherapy reactions. 26 The breakdown of the blood–retinal barrier and vascular hyperpermeability could result in vascular endothelial damage in response to retinal hypoxia and chronic ischemic condition, which may lead to radiation maculopathy. 27 In our study, the SVD remained stable and even slightly increased after conbercept injections until 6 months after plaque radiotherapy, indicating that retinal vascular damage in response to radiation therapy could be partly relieved by conbercept treatment.…”

Section: Discussionmentioning

confidence: 99%

Retinal Microvascular Changes in Uveal Melanoma Following Conbercept Injection After Plaque Radiotherapy as Detected by Optical Coherence Tomography Angiography

Yang

Wang²,

Chen³

et al. 2021

Retina

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Purpose: To investigate macular microvascular characteristics imaged by optical coherence tomography angiography in patients with uveal melanoma following conbercept injections after plaque radiotherapy. Methods: Prospective comparative analysis comprising 15 patients with uveal melanoma with conbercept injections and 30 patients without conbercept injections after plaque radiotherapy by optical coherence tomography angiography. The conbercept group received intravitreal conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal conbercept injection. Results: After initiation of conbercept injections, superficial retinal vascular density in the whole image and parafoveal region were significantly higher at 6 months, whereas there was no significant difference at 9 months and 12 months. In analysis of variance analysis, superficial retinal vascular density in the whole image remained stable after conbercept injections (P = 0.069), whereas the superficial retinal vascular density decreased significantly after plaque radiotherapy in the control group (P = 0.011). In multivariable linear regression, a higher superficial retinal vascular density in the whole image region at 6 months was significantly associated with intravitreal conbercept injection (P = 0.018), wider tumor base (P = 0.026), and thinner tumor thickness (P = 0.04). Conclusion: Optical coherence tomography angiography can provide a quantitative evaluation of early retinal microvascular changes after radiotherapy. Intravitreal conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma; however, it may not be able to provide long-term positive functional outcomes.

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“…A study involving 18 Chinese patients who underwent iodine-125 plaque therapy showed a significantly strong positive correlation of aqueous humor VEGF-A and PLGF levels with tumor thickness, and the correlation remained the same after radiation therapy [ 128 ]. Additionally, the expression of both growth factors increased after the surgery.…”

Section: Uveal Melanoma Biomarkers In Body Fluidsmentioning

confidence: 99%

Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications

Pašalić

Nikuševa-Martić

Sekovanić

et al. 2023

IJMS

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Uveal melanoma (UM) is rare, but it is the most common primary intraocular malignancy among adults. This review represents the molecular, genetic, and immunobiological mechanisms involved in UM carcinogenesis and progression, as well as data about the association of chromosomal changes, genetic mutations, selective proteins, and biochemical biomarkers with the clinical implications of UM. Genetic analysis has the potential to identify patients with a high risk of UM metastasis, enabling management that is more effective and allowing for the follow-up of patients. Advancements in molecular characterization of UM offer opportunities to develop targeted therapeutic strategies by focusing on relevant signaling pathways. Changes in miRNA expression could be useful in the diagnosis and prognosis of UM, due to unique miRNA profiles in melanoma cells or tissue and its association with metastasis. Although liver function tests do not provide enough data on the prognosis of UM, due to the high frequency of liver metastasis, liver function tests (LFTs) might be useful indicators; however, the absence of rising LFT values cannot lead to the exclusion of liver metastases. Molecular analysis of tumor tissue will allow us to identify patients with the added benefit of new therapeutic agents and provide a better insight into melanoma pathogenesis and its biological behavior.

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Elevated VEGF-A & PLGF concentration in aqueous humor of patients with uveal melanoma following Iodine-125 plaque radiotherapy

Cited by 8 publications

References 38 publications

Circulating tumor DNA tracking through driver mutations as a liquid biopsy-based biomarker for uveal melanoma

Circulating tumor DNA tracking through driver mutations as a liquid biopsy-based biomarker for uveal melanoma

Retinal Microvascular Changes in Uveal Melanoma Following Conbercept Injection After Plaque Radiotherapy as Detected by Optical Coherence Tomography Angiography

Genetic and Epigenetic Features of Uveal Melanoma—An Overview and Clinical Implications

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