Investigating intra-tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single-cell RNA sequencing

Jingyuan Huo , Zhen Wang , Wenting Zhao , Miao Chen , Haoyang Li , Fengpu He , Xiao Tian , Yaqi Ma , Firyuza Husanova , Liang Ma , Yiming Ni , Hongda Ding , Weidong Li , Hongfei Xu

Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (12) : e70113

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Clinical and Translational Medicine ›› 2024, Vol. 14 ›› Issue (12) : e70113 DOI: 10.1002/ctm2.70113
RESEARCH ARTICLE

Investigating intra-tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single-cell RNA sequencing

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Abstract

•Insights into the heterogeneity and transcriptional patterns of sarcoma cells may explain the challenges in treating primary cardiac angiosarcoma (PCAS) using the current therapeutic modalities.

•Characterization of the immune microenvironment revealed significant immunosuppression mediated by specific myeloid cell populations (SPP1+ and OLR1+ macrophages).

•Identification of mitochondrial dysfunction in immune cells within the PCAS microenvironment, particularly the notable downregulation of the MTRNR2L12 protein, suggests a new avenue for therapeutic targeting.

Keywords

heterogeneity / multicolour immunohistochemistry / primary cardiac angiosarcoma / single-cell RNA sequencing / tumour microenvironment

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Jingyuan Huo, Zhen Wang, Wenting Zhao, Miao Chen, Haoyang Li, Fengpu He, Xiao Tian, Yaqi Ma, Firyuza Husanova, Liang Ma, Yiming Ni, Hongda Ding, Weidong Li, Hongfei Xu. Investigating intra-tumoural heterogeneity and microenvironment diversity in primary cardiac angiosarcoma through single-cell RNA sequencing. Clinical and Translational Medicine, 2024, 14(12): e70113 DOI:10.1002/ctm2.70113

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References

[1]

SultanI, BiancoV, HabertheuerA, et al. Long-term outcomes of primary cardiac malignancies: multi-institutional results from the national cancer database. J Am Coll Cardiol. 2020; 75(18): 2338-2347.

[2]

SiontisBL, LejaM, ChughR. Current clinical management of primary cardiac sarcoma. Expert Rev Anticancer Ther. 2020; 20(1): 45-51.

[3]

RahoumaM, TafuniA, DabshaA, et al. Outcomes of surgery in cardiac angiosarcoma: a multi-institutional study from the National Cancer Database. JACC CardioOncol. 2023; 5(2): 259-261.

[4]

YinK, LuoR, WeiY, et al. Survival outcomes in patients with primary cardiac sarcoma in the United States. J Thorac Cardiovasc Surg. 2021; 162(1): 107-115.e2.

[5]

NassarAH, El-AmE, DenuR, et al. Clinical outcomes among immunotherapy-treated patients with primary cardiac soft tissue sarcomas: a multicenter retrospective study. JACC CardioOncol. 2024; 6(1): 71-79.

[6]

ZhouX, XuM, ZengW, et al. Combined effects of FH (E404D) and ACOX2 (R409H) cause metabolic defects in primary cardiac malignant tumor. Cell Death Discov. 2018; 4: 18.

[7]

LeducC, Jenkins SM, SukovWR, RustinJG, Maleszewski JJ. Cardiac angiosarcoma: histopathologic, immunohistochemical, and cytogenetic analysis of 10 cases. Hum Pathol. 2017; 60: 199-207.

[8]

GarciaJM, Gonzalez R, SilvaJM, et al. Mutational status of K-ras and TP53 genes in primary sarcomas of the heart. Br J Cancer. 2000; 82(6): 1183-1185.

[9]

KunzeK, Spieker T, GamerdingerU, et al. A recurrent activating PLCG1 mutation in cardiac angiosarcomas increases apoptosis resistance and invasiveness of endothelial cells. Cancer Res. 2014; 74(21): 6173-6183.

[10]

ZhangM, HuS, MinM, et al. Dissecting transcriptional heterogeneity in primary gastric adenocarcinoma by single cell RNA sequencing. Gut. 2021; 70(3): 464-475.

[11]

González-SilvaL, Quevedo L, VarelaI. Tumor functional heterogeneity unraveled by scRNA-seq technologies. Trends Cancer. 2020; 6(1): 13-19.

[12]

LiR, Ferdinand JR, LoudonKW, et al. Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer. Cancer Cell. 2022; 40(12): 1583-1599.e10.

[13]

TangF, LiJ, QiL, et al. A pan-cancer single-cell panorama of human natural killer cells. Cell. 2023; 186(19): 4235-4251.e20.

[14]

KirschenbaumD, XieK, IngelfingerF, et al. Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma. Cell. 2024; 187(1): 149-165.e23.

[15]

WangL, LiuY, DaiY, et al. Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment. Gut. 2023; 72(5): 958-971.

[16]

KimR, AnM, LeeH, et al. Early tumor-immune microenvironmental remodeling and response to first-line fluoropyrimidine and platinum chemotherapy in advanced gastric cancer. Cancer Discov. 2022; 12(4): 984-1001.

[17]

WangX, MiaoJ, WangS, et al. Single-cell RNA-seq reveals the genesis and heterogeneity of tumor microenvironment in pancreatic undifferentiated carcinoma with osteoclast-like giant-cells. Mol Cancer. 2022; 21(1): 133.

[18]

Van de SandeB, FlerinC, DavieK, et al. A scalable SCENIC workflow for single-cell gene regulatory network analysis. Nat Protoc. 2020; 15(7): 2247-2276.

[19]

MorabitoS, Miyoshi E, MichaelN, et al. Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer’s disease. Nat Genet. 2021; 53(8): 1143-1155.

[20]

BrowaeysR, Saelens W, SaeysY. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat Methods. 2020; 17(2): 159-162.

[21]

LitviňukováM, Talavera-LópezC, Maatz H, et al. Cells of the adult human heart. Nature. 2020; 588(7838): 466-472.

[22]

EfremovaM, Vento-Tormo M, TeichmannSA, Vento-TormoR. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat Protoc. 2020; 15(4): 1484-1506.

[23]

DannE, Henderson NC, TeichmannSA, MorganMD, Marioni JC. Differential abundance testing on single-cell data using k-nearest neighbor graphs. Nat Biotechnol. 2022; 40(2): 245-253.

[24]

CrowellHL, Soneson C, GermainPL, et al. Muscat detects subpopulation-specific state transitions from multi-sample multi-condition single-cell transcriptomics data. Nat Commun. 2020; 11(1): 6077.

[25]

QiuX, MaoQ, TangY, et al. Reversed graph embedding resolves complex single-cell trajectories. Nat Methods. 2017; 14(10): 979-982.

[26]

SunL, ShiL, LiW, et al. JFK, a Kelch domain-containing F-box protein, links the SCF complex to p53 regulation. Proc Natl Acad Sci U S A. 2009; 106(25): 10195-200.

[27]

XiaoW, WangJ, WangX, et al. Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression. Autophagy. 2022; 18(11): 2615-2635.

[28]

KhanMA, KhanP, AhmadA, Fatima M, NasserMW. FOXM1: A small fox that makes more tracks for cancer progression and metastasis. Semin Cancer Biol. 2023; 92: 1-15.

[29]

AlthofN, Harkins S, KemballCC, FlynnCT, Alirezaei M, WhittonJL. In vivo ablation of type I interferon receptor from cardiomyocytes delays coxsackieviral clearance and accelerates myocardial disease. J Virol. 2014; 88(9): 5087-5099.

[30]

BillR, Wirapati P, MessemakerM, et al. CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers. Science. 2023; 381(6657): 515-524.

[31]

ZhangP, ZhaoY, XiaX, et al. Expression of OLR1 gene on tumor-associated macrophages of head and neck squamous cell carcinoma, and its correlation with clinical outcome. Oncoimmunology. 2023; 12(1): 2203073.

[32]

DeMartinoJ, Meister MT, VisserLL, et al. Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma. Nat Commun. 2023; 14(1): 3074.

[33]

LuY, ChenD, WangB, et al. Single-cell landscape of undifferentiated pleomorphic sarcoma. Oncogene. 2024; 43(18): 1353-1368.

[34]

TessaroFHG, KoEY, De SimoneM, et al. Single-cell RNA-seq of a soft-tissue sarcoma model reveals the critical role of tumor-expressed MIF in shaping macrophage heterogeneity. Cell Rep. 2022; 39(12): 110977.

[35]

ZhouY, YangD, YangQ, et al. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma. Nat Commun. 2020; 11(1): 6322.

[36]

CilloAR, Mukherjee E, BaileyNG, et al. Ewing Sarcoma and Osteosarcoma Have Distinct Immune Signatures and Intercellular Communication Networks. Clin Cancer Res. 2022; 28(22): 4968-4982.

[37]

ElhananiO, Ben-Uri R, KerenL. Spatial profiling technologies illuminate the tumor microenvironment. Cancer Cell. 2023; 41(3): 404-420.

[38]

ParkJ, HsuehPC, LiZ, HoPC. Microenvironment-driven metabolic adaptations guiding CD8+ T cell anti-tumor immunity. Immunity. 2023; 56(1): 32-42.

[39]

YuanLL, ChenZ, QinJ, et al. Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient. Front Immunol. 2022; 13: 1019870.

[40]

WisdomAJ, MoweryYM, HongCS, et al. Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy. Nat Commun. 2020; 11(1): 6410.

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2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

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