The tumor microenvironment may trigger lymphoproliferation in cardiac myxoma

Eugeniu Jantuan; Brian Chiu; Bonnie Chiu; Fan Shen; Gavin Y Oudit; Consolato Sergi

doi:10.1016/j.tranon.2020.100911

The tumor microenvironment may trigger lymphoproliferation in cardiac myxoma

Transl Oncol. 2021 Jan;14(1):100911. doi: 10.1016/j.tranon.2020.100911. Epub 2020 Oct 23.

Authors

Eugeniu Jantuan¹, Brian Chiu¹, Bonnie Chiu¹, Fan Shen¹, Gavin Y Oudit², Consolato Sergi³

Affiliations

¹ Department of Laboratory Medicine and Pathology, University of Alberta Hospital, 8440-112 Street, Edmonton T6G 2B7, Alberta, Canada.
² Department of Medicine, Division of Cardiology, Mazankowski Alberta Heart Institute, Edmonton, AB, Canada.
³ Department of Laboratory Medicine and Pathology, University of Alberta Hospital, 8440-112 Street, Edmonton T6G 2B7, Alberta, Canada; Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; National "111″ Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering, Hubei University of Technology, Wuhan, Hubei, China; Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China. Electronic address: sergi@ualberta.ca.

Abstract

Cardiac myxomas (CM) and primary cardiac lymphoproliferative disorders (LPD) are rare primary cardiac neoplasms. The composite occurrence of LPD in CM has been occasionally reported, and chronic inflammation in response to viral infection has been suggested to be at the basis of oncogenesis. Cancers can upregulate autophagy to endure microenvironmental stress and to increase local growth and aggressiveness. CM exhibit a dichotomous separation in low and high inflammatory grades (LIG vs. HIG). We studied 23 CMs using autophagy-related proteins and NanoString technology for gene expression. Autophagy-related proteins (Beclin-1, LAMP-1, LC3, and p62) were demonstrated in both tumor and stromal cells. ATG genes showed a progression of involvement in CM using an 8-gene signature. They were associated with Epstein-Barr virus (EBV) encoded latent membrane protein 1 (EBV LMP1) activation. We suggest that CM can upregulate autophagy, creating a favorable environment for EBV-driven oncogenesis. To the best of our knowledge, the present study is the first to report on the TME using the expression of autophagy-related genes and proteins in CM. The microenvironment of CM is dynamic, with a variety of cell types and different molecular pathways at play, and this study may clearly warrant further investigation.

Keywords: Autophagy; Autophagy-inflammation interplay; Cardiac myxoma; Lymphoproliferative disorder; Tumor microenvironment.