Metastasis of Uveal Melanoma with Monosomy-3 Is Associated with a Less Glycogenetic Gene Expression Profile and the Dysregulation of Glycogen Storage

TY - JOUR

T1 - Metastasis of Uveal Melanoma with Monosomy-3 Is Associated with a Less Glycogenetic Gene Expression Profile and the Dysregulation of Glycogen Storage

AU - Vardanyan, Siranush

AU - Brosig, Anton

AU - Merz, Hartmut

AU - Ranjbar, Mahdy

AU - Kakkassery, Vinodh

AU - Grisanti, Salvatore

AU - Tura, Aysegül

PY - 2020/7/29

Y1 - 2020/7/29

N2 - The prolonged storage of glucose as glycogen can promote the quiescence of tumor cells, whereas the accumulation of an aberrant form of glycogen without the primer protein glycogenin can induce the metabolic switch towards a glycolytic phenotype. Here, we analyzed the expression of n = 67 genes involved in glycogen metabolism on the uveal melanoma (UM) cohort of the Cancer Genome Atlas (TCGA) study and validated the differentially expressed genes in an independent cohort. We also evaluated the glycogen levels with regard to the prognostic factors via a differential periodic acid-Schiff (PAS) staining. UMs with monosomy-3 exhibited a less glycogenetic and more insulin-resistant gene expression profile, together with the reduction of glycogen levels, which were associated with the metastases. Expression of glycogenin-1 (Locus: 3q24) was lower in the monosomy-3 tumors, whereas the complementary isoform glycogenin-2 (Locus: Xp22.33) was upregulated in females. Remarkably, glycogen was more abundant in the monosomy-3 tumors of male versus female patients. We therefore provide the first evidence to the dysregulation of glycogen metabolism as a novel factor that may be aggravating the course of UM particularly in males.

AB - The prolonged storage of glucose as glycogen can promote the quiescence of tumor cells, whereas the accumulation of an aberrant form of glycogen without the primer protein glycogenin can induce the metabolic switch towards a glycolytic phenotype. Here, we analyzed the expression of n = 67 genes involved in glycogen metabolism on the uveal melanoma (UM) cohort of the Cancer Genome Atlas (TCGA) study and validated the differentially expressed genes in an independent cohort. We also evaluated the glycogen levels with regard to the prognostic factors via a differential periodic acid-Schiff (PAS) staining. UMs with monosomy-3 exhibited a less glycogenetic and more insulin-resistant gene expression profile, together with the reduction of glycogen levels, which were associated with the metastases. Expression of glycogenin-1 (Locus: 3q24) was lower in the monosomy-3 tumors, whereas the complementary isoform glycogenin-2 (Locus: Xp22.33) was upregulated in females. Remarkably, glycogen was more abundant in the monosomy-3 tumors of male versus female patients. We therefore provide the first evidence to the dysregulation of glycogen metabolism as a novel factor that may be aggravating the course of UM particularly in males.

U2 - 10.3390/cancers12082101

DO - 10.3390/cancers12082101

M3 - SCORING: Journal article

C2 - 32751097

VL - 12

JO - CANCERS

JF - CANCERS

SN - 2072-6694

IS - 8

M1 - 2101

ER -