Abstract 3603: Differential gene expression of metastatic and non-metastatic human uveal melanoma

Introduction: Uveal melanoma (UM) is the most common intraocular malignancy arises in uvea. Most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. UM has been attributed to diverse causes but the real mechanism underlying this cancer development remains obscure. Elucidation of such mechanism requires thorough knowledge of the genes involved and their regulation strategies. Gene expression is one such study that helps to uncover the interactions between the genes, and ultimately the impact on the pathology of the disease. Thus, the aim of this study is to identify the differentially expressed genes involved in the mechanism of tumorigenesis of uveal melanoma. Material and Methods: Tissue samples from patients with uveal melanoma (non-metastatic and metastatic) were collected as cases and normal uveal tissue from cadaver eyes served as control. Microarray analysis was performed by categorising the patients into two groups (non-metastatic uveal melanoma vs normal uvea and metastatic uveal melanoma vs non-metastatic uveal melanoma) by using human HT12-v4 expression beadchip. The semiquantitative RT-PCR was performed on uveal melanoma tissue samples and normal uveal to confirm the significantly expressed genes obtained in microarray analysis. Results: Gene expression analysis of non-metastatic human uveal melanoma and normal uveal tissues identified total 1512 differentially expressed genes out of which 1374 genes were upregulated while 138 genes were downregulated. Gene expression analysis of metastatic human uveal melanoma and non-metastatic human uveal melanoma tissues identified total 1272 differentially expressed genes out of which 130 genes were upregulated and 1142 genes were downregulated. The mRNA expression (semiquantitative RT-PCR) in non-metastatic human uveal melanoma and normal uvea showed that the mean mRNA expression levels of FRAP1 (fold change=11.49±0.33, p=0.0046), c-JUN (fold change=10.40±0.25, p=0.0053) and TIMP3 (fold change=-16.03±0.04, p=0.0043) were significantly altered. In metastatic and non-metastatic human uveal melanoma, mean mRNA expression levels of FRAP1 (fold change=4.56±0.34, p=0.0372), c-JUN (fold change=3.91±0.25, p=0.0052), TIMP3 (fold change=-7.66±0.56, p=0.0046) were also significantly altered. Conclusion: A comparative analysis of the microarray gene expression data revealed genes belonging to particular biological pathways viz. MAPK signaling pathway, PI3K/AKT/mTOR signaling pathway, Fas/FasL pathway, CDK regulation of DNA replication and p53 signaling pathway were dysregulated in uveal melanoma. The significant mRNA expression of FRAP1, c-JUN and TIMP3 may act as biomarkers which will help in the diagnosis/prognosis of this eye tumor. But further investigation needed in large cohort. Citation Format: Sooraj K, Sandeep Goswami, Sunil Kumar, Swati Shukla, Neelam Pushker, Jasbir Kaur. Differential gene expression of metastatic and non-metastatic human uveal melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3603.