Immune classification and identification of prognostic genes for uveal melanoma based on six immune cell signatures

Abstract

Cutaneous melanoma could be treated by immunotherapy, which only has limited efficacy on uveal melanoma (UM). UM immunotyping for predicting immunotherapeutic responses and guiding immunotherapy should be better understood. This study identified molecular subtypes and key genetic markers associated with immunotherapy through immunosignature analysis. We screened a 6-immune cell signature simultaneously correlated with UM prognosis. Three immune subtypes (IS) were determined based on the 6-immune cell signature. Overall survival (OS) of IS3 was the longest. Significant differences of linear discriminant analysis (LDA) score were detected among the three IS types. IS3 with the highest LDA score showed a low immunosuppression. IS1 with the lowest LDA score was more immunosuppressive. LDA score was significantly negatively correlated with most immune checkpoint-related genes, and could reflect UM patients’ response to anti-PD1 immunotherapy. Weighted correlation network analysis (WGCNA) identified that salmon, purple, yellow modules were related to IS and screened 6 prognostic genes. Patients with high-expressed NME1 and TMEM255A developed poor prognosis, while those with high-expressed BEX5 and ROPN1 had better prognosis. There was no notable difference in OS between patients with high-expressed LRRN1 and ST13 and those with low-expressed LRRN1 and ST13. NME1, TMEM255A, Bex5 and ROPN1 showed potential prognostic significance in UM.

Machine Learning Methods for Gene Selection in Uveal Melanoma

“…CHL1 was found to be one of the most downregulated genes in UM that metastasized to the liver compared to non-metastatic tumors [22]. ROPN1 has previously been described as related to good prognosis when overexpressed in the UM TCGA dataset [23]; however, in the Piaggio et al dataset [17], several metastatic patients have high expression levels of this gene (Figures S2 and S3). Among the genes selected by CNAPE and DF, we can find several genes related to worse prognosis.…”

Advances in immunotyping of colorectal cancer

“…The characteristics of immune infiltration have been explored in tumors stratified into different risk groups based on prognostic factors. For instance, three immune subtypes have been determined based on a signature comprising six immune types of cells associated with the prognosis of uveal melanoma ( 95 ). Immune subtype 3 had the highest LDA score that reflected a response to anti-PD1 immunotherapy, where immune subtype 1 had the lowest LDA score reflecting an immunosuppressive phenotype.…”

Construction of novel 7 integrin-related gene signatures in thyroid cancer construction of model based on integrin genes

“…BEX5 belongs to the human brain-expressed X-linked family, which played an essential role in the cell cycle and apoptosis. [21] Although the function of other members of the BEX family was confirmed as an oncogene or tumor suppressor, [22][23][24][25] and studies showed that BEX5 was lowly expressed and related to the poor prognosis in uveal melanoma and lung adenocarcinoma, [21,26] there were fewer studies about the effect of BEX5 on the progress of cancers. In this study, we found BEX5 was significantly downregulated in the THCA tissues compared with normal tissues because of the CNV to some extent.…”