Metastasis of uveal melanoma with monosomy-3 is associated with a less glycogenetic gene expression profile and the dysregulation of glycogen storage

Siranush Vardanyan, Anton Brosig, Hartmut Merz, Mahdy Ranjbar, Vinodh Kakkassery, Salvatore Grisanti, Aysegül Tura*

*Corresponding author for this work

Abstract

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.

Original languageEnglish
Article number2101
JournalCancers
Volume12
Issue number8
Pages (from-to)1-25
Number of pages25
DOIs
Publication statusPublished - 29.07.2020

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)

Fingerprint

Dive into the research topics of 'Metastasis of uveal melanoma with monosomy-3 is associated with a less glycogenetic gene expression profile and the dysregulation of glycogen storage'. Together they form a unique fingerprint.

Cite this