Prognostic analysis of uveal melanoma based on the characteristic genes of M2-type macrophages in the tumor microenvironment

Abstract

Uveal melanoma arises from stromal melanocytes and is the most prevalent primary intraocular tumor in adults. It poses a significant diagnostic and therapeutic challenge due to its high malignancy and early onset of metastases. In recent years, there has been a growing interest in the role of diverse immune cells in tumor cell development and metastasis. Using The Cancer Genome Atlas and the gene expression omnibus databases, and the CIBERSORT method, we investigated the topography of intra-tumor immune infiltration in uveal melanoma in this research. We evaluated the prognosis of uveal melanoma patients using the M2 macrophage immune cell infiltration score in conjunction with clinical tumor patient data. We built a prognostic model based on the distinctive genes of M2 macrophages and combined it with patients’ clinical data in the database; we ran a survival prognostic analysis to authenticate the model’s accuracy. The functional study revealed the importance of macrophage-associated genes in the development of uveal melanoma. Moreover, the reliability of our prediction model was verified by combining tumor mutational load, immune checkpoint, and drug sensitivity, respectively. Our study provides a reference for the follow-up study of uveal melanoma.

Recent Advances in Molecular and Genetic Research on Uveal Melanoma

“…Indeed, in UMs with monosomy 3, TAMs are primarily of the proangiogenic M2 polarization type [ 130 , 131 ]. RNA sequencing data from 63 UM cases has established a M2-macrophage-specific prognostic signature: CCL18, SIGLEC7, CD300LF, CAPG, LILRA4, SDS, and FAHD2CP, associated with high-risk UM groups [ 132 ]. The expression levels of these mRNA transcripts were linked with clinical data of tumor patients, including tumor mutational load, immune checkpoints, and drug sensitivity [ 132 ].…”

“…RNA sequencing data from 63 UM cases has established a M2-macrophage-specific prognostic signature: CCL18, SIGLEC7, CD300LF, CAPG, LILRA4, SDS, and FAHD2CP, associated with high-risk UM groups [ 132 ]. The expression levels of these mRNA transcripts were linked with clinical data of tumor patients, including tumor mutational load, immune checkpoints, and drug sensitivity [ 132 ]. In addition, a MUM prognostic model using immune and stromal index was constructed ( n = 63 participants), that included a down-expression of HLA-J, MMP12, HES6, and ADAMDEC1 mRNA transcripts [ 133 ].…”