Inflammation‐related MiRNAs are associated with Monosomy 3 in Uveal Melanoma

Abstract

PurposeInflammation is a bad prognostic sign in Uveal Melanoma (UM), but it is as yet unclear how it is regulated. We set out to investigate the relation between microRNA’s and inflammation in UM and their potential regulation by chromosome 3 and 8.MethodsThe expression of 125 microRNA’s was determined using an Illumina HT12V4 array in 64 primary UM. Similarly, the mRNA expression of HLA‐A, HLA‐B and markers of tumor‐infiltrating lymphocytes (TIL) such as CD3E, CD4, CD8, and tumor‐associated macrophages (TAM), such as CD68 and CD163, was obtained from the array.ResultsWhen looking at all 64 UM tumors, expression levels of seven of the 125 miRNA’s that were analysed correlated with the presence of tumor‐infiltrating lymphocytes (TIL), tumor‐associated macrophages (TAM) and HLA Class I expression. Increased levels of miRNA 22 and 155 were associated with increased HLA expression and high numbers of TIL and TAM, while expression of miRNAs 7, 98, 125, 302 and 599 was associated with less infiltrate and a lower HLA expression. MiRNAs 22 (p ≤ 0.001) and 155 (p = 0.005) were upregulated in monosomy 3 tumors and expression of miRNAs 7 (p = 0.35), 98 (p = 0.26), 125 (p = 0.91) and 599 (p = 0.80) was not related to monosomy 3, while miR‐302 (p = 0.02) was slightly higher in D3 tumors. MiR‐22 was positively associated to chromosome 8q gain (p = 0.01) but miRNA’s 7 (p = 0.004), 98 (p = 0.002), 125 (p = 0.005), 302 (p = 0.02), and 599 (p ≤ 0.001) were all decreased in tumours with 8q gain.ConclusionsWe identified a set of microRNA’s associated with inflammatory markers (HLA Class I, TIL’s and TAM’s) in UM. The microRNA’s that are positively associated with inflammation are highly expressed in tumors with one copy of chromosome 3 and 8q gain while this is the opposite for microRNA’s negatively associated with inflammation. We propose a regulatory role for chromosome 3 and 8q abnormality in the control of inflammation‐related microRNA’s and suggest a potential involvement of these microRNA’s in the development of inflammation in UM.