Vitreous microRNA levels as diagnostic biomarkers for vitreoretinal lymphoma

Kakkassery, Vinodh; Schroers, Roland; Coupland, Sarah E.; Wunderlich, M. I.; Schargus, Marc; Heinz, Carsten; Wasmuth, Susanne; Heiligenhaus, Arnd; Ahle, Guido; Lenoble, P.; Schlegel, Uwe; Schmiegel, Wolff; Dick, H. Burkhard; Baraniskin, Alexander

doi:10.1182/blood-2017-01-765180

Cited by 33 publications

(24 citation statements)

References 19 publications

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“…; Kakkassery et al. ). Further validation of the combined cellular and cytokine signature is required in vitreous specimens of a new cohort of patients with chronic uveitis.…”

Section: Discussionmentioning

confidence: 98%

Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma

Hoog

Dik

Heezen

et al. 2019

Acta Ophthalmologica

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Purpose Primary vitreoretinal lymphoma [(P)VRL]) is a rare malignancy of the eye localized in the retina, vitreous or choroid. Here, we aim to determine the value of the combination of innovative diagnostic methods for accurate differentiation between (P)VRL and non‐(P)VRL in patients with suspect uveitis or vitritis. Methods Multicolour flow cytometric immunophenotyping of cells in the vitreous samples was performed using the EuroFlow small sample tube. Additionally, cytokines/chemokines and growth factors were measured in the vitreous specimens using a multiplex immunoassay. Data were evaluated in predefined clinical subgroups using omniviz unsupervised Pearson's correlation visualization and unsupervised heatmap analysis. Results A total of 53 patients were prospectively included in the period 2012–2015. In the (P)VRL subgroup (n = 10), nine cases showed aberrant surface membrane immunoglobulin (SmIg) light chain expression. In the non‐(P)VRL group (n = 43) clearly skewed SmIg light chain expression was observed in two multiple sclerosis‐related uveitis cases, but not in other uveitis types. Soluble mediator measurement revealed high interleukin (IL)‐10/IL‐6 ratios, and high IL‐1RA levels in 9/10 (P)VRL cases, but not in any non‐(P)VRL case. Further correlation and heatmap analysis revealed a minimal signature of cellular parameters (CD19+ B cells, aberrant SmIg light chain expression) and cytokine parameters (IL‐10/IL‐6 ratio >1, high IL‐10, high IL‐1 RA, high monocyte chemotactic protein‐1, high macrophage inflammatory protein‐1β) to reliably distinguish (P)VRL from non‐(P)VRL. Conclusion Here, we show the power of a combined cellular and proteomics strategy for detecting (P)VRL in vitreous specimens, especially in cases with minor cellular (P)VRL infiltrates.

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“…; Kakkassery et al. ). Further validation of the combined cellular and cytokine signature is required in vitreous specimens of a new cohort of patients with chronic uveitis.…”

Section: Discussionmentioning

confidence: 98%

Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma

Hoog

Dik

Heezen

et al. 2019

Acta Ophthalmologica

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“…Accumulating evidence have shown that miRNA could function as important modulators in tumorigenesis 21 , 22 , emerged as oncogenes or tumor suppressors, via different target genes. Detection of specific miRNAs in urine, blood, or tissue samples could serve as novel biomarkers and contributed to tumor diagnosis and clinical outcome prediction 23 – 26 .…”

Section: Discussionmentioning

confidence: 99%

The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis

et al. 2018

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The abnormal expression of microRNAs (miRNAs) in colorectal cancer (CRC) progression has been widely investigated. It was reported that the same hairpin RNA structure could generate mature products from each strand, termed 5p and 3p, which binds different target mRNAs. Here, we explored the expression, functions, and mechanisms of miR-514b-3p and miR-514b-5p in CRC cells and tissues. We found that miR-514b-3p was significantly down-regulated in CRC samples, and the ratio of miR-514b-3p/miR-514b-5p increased from advanced CRC, early CRC to matched normal colorectal tissues. Follow-up functional experiments illustrated that miR-514b-3p and miR-514b-5p had distinct effects through interacting with different target genes: MiR-514b-3p reduced CRC cell migration, invasion and drug resistance through increasing epithelial marker and decreasing mesenchymal marker expressions, conversely, miR-514b-5p exerted its pro-metastatic properties in CRC by promoting EMT progression. MiR-514b-3p overexpressing CRC cells developed tumors more slowly in mice compared with control cells, however, miR-514b-5p accelerated tumor metastasis. Overall, our data indicated that though miR-514b-3p and miR-514b-5p were transcribed from the same RNA hairpin, each microRNA has distinct effect on CRC metastasis.

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“…Results identified only miR‐155 as differentially expressed, and in contrast to the setting of systemic diffuse large B‐cell lymphoma, the level was significantly lower in samples from patients with vitreoretinal lymphoma in comparison to uveitis controls. In 2017, Kakkassery et al . directed an investigation towards levels of three miRNA – miR‐19b, miR‐21 and miR‐92 – which they had previously measured at increased levels in cerebrospinal fluid from patients with primary CNS lymphoma.…”

Section: Micrornamentioning

confidence: 99%

“…65 Recently peer-reviewed studies from different groups have addressed the potential application of miRNA in the diagnosis of vitreoretinal lymphoma. In 2014, Tuo et al 66 67 directed an investigation towards levels of three miRNA -miR-19b, miR-21 and miR-92which they had previously measured at increased levels in cerebrospinal fluid from patients with primary CNS lymphoma. Vitreous supernatant samples from 10 patients with histopathologically diagnosed vitreoretinal lymphoma, 40 patients with uveitis and seven patients with macular epiretinal membrane were compared: levels of all three miRNA were significantly higher in tumour cases than noninflamed and uveitis control samples.…”

Section: Micrornamentioning

confidence: 99%

Emerging diagnostic tests for vitreoretinal lymphoma: a review

Dawson

Williams

Appukuttan

et al. 2018

Clinical Exper Ophthalmology

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Vitreoretinal lymphoma, which most commonly is diffuse large B-cell non-Hodgkin in type, is a rare cancer with high morbidity and high mortality. Making a tissue diagnosis of vitreoretinal lymphoma is a major challenge for clinicians due to biological and technical factors. Yet, the delay in start of treatment may have vision- and life-threatening consequences, and there is considerable interest in the application of molecular assays to improve the accuracy of the diagnostic process: detection of a clonal immunoglobulin heavy-chain rearrangements in lymphoma cells by polymerase chain reaction; measurement of vitreous or aqueous interleukin-10 protein levels in ocular fluids; and identification of mutations in the myeloid differentiation primary response gene 88 in tumour cells. In this article, we review the historical development and current application of each of these molecular methods. We also discuss future opportunities for the molecular diagnosis of vitreoretinal lymphoma through next-generation sequencing technologies.

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Vitreous microRNA levels as diagnostic biomarkers for vitreoretinal lymphoma

Cited by 33 publications

References 19 publications

Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma

Combined cellular and soluble mediator analysis for improved diagnosis of vitreoretinal lymphoma

The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis

Emerging diagnostic tests for vitreoretinal lymphoma: a review

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