Jantuan Eugeniu, Chiu Brian, Chiu Bonnie, Shen Fan, Oudit Gavin Y, Sergi Consolato
Department of Laboratory Medicine and Pathology, University of Alberta Hospital, 8440-112 Street, Edmonton T6G 2B7, Alberta, Canada.
Department of Medicine, Division of Cardiology, Mazankowski Alberta Heart Institute, Edmonton, AB, Canada.
Transl Oncol. 2021 Jan;14(1):100911. doi: 10.1016/j.tranon.2020.100911. Epub 2020 Oct 23.
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.
心脏黏液瘤（CM）和原发性心脏淋巴增殖性疾病（LPD）是罕见的原发性心脏肿瘤。CM中LPD的复合发生情况偶尔有报道，并且有人提出病毒感染引起的慢性炎症是肿瘤发生的基础。癌症可上调自噬以耐受微环境应激并增加局部生长和侵袭性。CM在低炎症等级和高炎症等级（低炎症等级与高炎症等级）之间呈现二分法分离。我们使用自噬相关蛋白和NanoString技术对23例CM进行基因表达研究。自噬相关蛋白（Beclin-1、LAMP-1、LC3和p62）在肿瘤细胞和基质细胞中均有表达。利用一个8基因特征，自噬相关基因（ATG）显示出在CM中的参与进展。它们与爱泼斯坦-巴尔病毒（EBV）编码的潜伏膜蛋白1（EBV LMP1）激活有关。我们认为CM可上调自噬，为EBV驱动的肿瘤发生创造有利环境。据我们所知，本研究首次报道了利用CM中自噬相关基因和蛋白的表达来研究肿瘤微环境。CM的微环境是动态的，有多种细胞类型和不同的分子途径在起作用，本研究可能确实值得进一步研究。
