Journal of Inflammation Research (Jan 2022)

Single Nuclear RNA Sequencing Highlights Intra-Tumoral Heterogeneity and Tumor Microenvironment Complexity in Testicular Embryonic Rhabdomyosarcoma

  • Xu X,
  • Liu Z,
  • Li Y,
  • Fan L,
  • Wang S,
  • Guo J,
  • Luo Y,
  • Bo H

Journal volume & issue
Vol. Volume 15
pp. 493 – 507

Abstract

Read online

Xuezheng Xu,1,* Zhizhong Liu,2,* Yi Li,3 Liqing Fan,4,5 Shuang Wang,6 Jie Guo,7 Yanwei Luo,8 Hao Bo4,5 1Department of Orthopaedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People’s Republic of China; 2Department of Urology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People’s Republic of China; 3Department of Obstetrics, The First Hospital of Changsha, Changsha, 410005, People’s Republic of China; 4Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410078, People’s Republic of China; 5NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, 410078, People’s Republic of China; 6Medical Research Center and Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 7National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 8Department of Blood Transfusion, the Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yanwei Luo; Hao Bo Email [email protected]; [email protected]: Testicular embryonic rhabdomyosarcoma (ERMS) is a rare soft tissue tumor in children featured with high intra-tumoral heterogeneity. In this study, we aimed to comprehensively delineate the testicular ERMS intra-tumoral heterogeneity and tumor microenvironment.Methods: Cell types and the corresponding marker genes were identified by single-nuclear RNA sequencing (snRNA-seq). Functional states of different clusters were evaluated by uniform manifold approximation and projection and differentially expressed genes. Kaplan–Meier curve analysis was constructed according to the gene expression profile to determine the correlation between candidate marker genes and the overall survival and disease-free survival of patients with osteosarcoma from TCGA.Results: A total of 8868 tumor cells and 10,147 normal cells were obtained from testicular ERMS tissues. The heterogeneous malignant subtype was composed of six subgroups (C1–C6) with differential proliferative and migratory potentials. Cell trajectory analysis revealed the C1 subgroup might be the starting cells of the tumor and transform into two different types of malignant cells, C2 and C5/6, during the development of RMS. The differentially expressed genes were closely related to cell adhesion and extracellular matrix signaling pathways. Furthermore, the interaction analysis between cell subgroups (macrophages and tumor cells, endothelial cells and tumor cells) demonstrated that collagen-related gene COL6A1 plays a key role from the initiation of ERMS to the entire process of malignant transformation.Conclusion: Our findings provide a new insight in the understanding of the initiation and progression of testicular ERMS and have potential value in the development of markers for the diagnosis and stratification of testicular ERMS.Keywords: embryonic rhabdomyosarcoma, intra-tumoral heterogeneity, biomarker, extracellular matrix, tumor microenvironment

Keywords