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On-line Access: 2024-08-27

Received: 2023-10-17

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Junfen XU

https://orcid.org/0000-0002-2377-0775

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Journal of Zhejiang University SCIENCE B

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Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma


Author(s):  Junfen XU, Mengyan TU

Affiliation(s):  Department of Gynecologic Oncology, Womens Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; more

Corresponding email(s):  xjfzu@zju.edu.cn

Key Words:  Ovarian carcinosarcoma; Single-cell RNA sequencing (scRNA-seq); Tumor heterogeneity


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Junfen XU, Mengyan TU. Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300407

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author="Junfen XU, Mengyan TU",
journal="Journal of Zhejiang University Science B",
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doi="https://doi.org/10.1631/jzus.B2300407"
}

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%T Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma
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%A Mengyan TU
%J Journal of Zhejiang University SCIENCE B
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%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2300407"

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T1 - Single-cell transcriptomics reveals tumor landscape in ovarian carcinosarcoma
A1 - Junfen XU
A1 - Mengyan TU
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PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2300407"


Abstract: 
ObjectiveThe present study used single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of ovarian carcinosarcoma (OCS) and identify its molecular characteristics.
MethodsscRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor microenvironment. Immunohistochemistry staining was used for validation. The scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma (HGSOC) tumors and other OCS tumors.
ResultsBoth malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this study. We identified four epithelial cell subclusters with different biological roles. Among them, epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog (BRCA1) and DNA topoisomerase 2-α (TOP2A) expression and was related to drug resistance and cell cycle. We analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor (FGF) and pleiotrophin (PTN) signalings were the main pathways contributing to communication between these cells. Moreover, we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS data. All the epithelial subclusters in the OCS tumor could be found in the HGSOC samples. Notably, the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor, characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1), collagen type XXIII α1 chain (COL23A1), cholecystokinin (CCK), bone morphogenetic protein 7 (BMP7), PTN, Wnt inhibitory factor 1 (WIF1), and insulin-like growth factor 2 (IGF2). Moreover, this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian tissue.
ConclusionsThis study provides the single-cell transcriptomics signature of human OCS, which constitutes a new resource for elucidating OCS diversity.

单细胞转录组学揭示卵巢癌肉瘤的肿瘤特征

许君芬1,2,屠梦雁1
1浙江大学医学院附属妇产科医院妇科肿瘤科,中国杭州市,310006
2浙江省妇产疾病临床医学研究中心,中国杭州市,310006
摘要:本研究旨在通过使用单细胞RNA测序(scRNA-seq)来表征卵巢癌肉瘤的细胞组成并鉴定其分子特征。我们将scRNA-seq应用于手术切除的原发性卵巢癌肉瘤标本,对肿瘤细胞和肿瘤微环境进行分析,同时采用免疫组织化学染色进行验证,最后将卵巢癌肉瘤的scRNA-seq数据与高级别浆液性卵巢癌肿瘤及其他研究中的卵巢癌肉瘤数据进行比较。结果显示,在该卵巢癌肉瘤患者中可同时检测到恶性上皮细胞和恶性间充质细胞。我们鉴定了四个具有不同生物学作用的上皮细胞亚簇,其中上皮细胞亚簇4表现出高水平的乳腺癌1号基因(BRCA1)和DNA拓扑异构酶II α(TOP2A)表达,这与耐药性和细胞周期有关。通过对上皮细胞和间充质细胞之间的相互作用分析,我们还发现成纤维细胞生长因子(FGF)和多功能生长因子(PTN)信号通路是促进这种细胞通讯的主要途径。此外,通过将这种卵巢癌肉瘤的恶性上皮和间充质细胞与课题组前期发表的高级别浆液性卵巢癌scRNA-seq数据及其他已发表的卵巢癌肉瘤数据进行对比,我们发现在高级别浆液性卵巢癌样本中存在该卵巢癌肉瘤中的所有上皮亚簇。值得注意的是,间充质亚簇C14在卵巢癌肉瘤中表现出特异性表达模式,其特征是肽基丙基异构酶24A1(CYP24A1)、胶原XXIII型α1链(COL23A1)、胆囊收缩素(CCK)、骨形态发生蛋白7(BMP7)、PTN、Wnt抑制因子1(WIF1)和胰岛素样生长因子2(IGF2)表达水平的升高;当与另一份已发表的卵巢癌肉瘤数据及正常卵巢组织相比,该亚簇则表现出截然不同的特征。综上,本研究提供了人类卵巢癌肉瘤的单细胞转录组特征,并为阐明卵巢癌肉瘤多样性提供了新的资源。

关键词组:卵巢癌肉瘤;单细胞RNA测序;肿瘤异质性

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AriyoshiK, KawauchiS, KakuT, et al., 2000. Prognostic factors in ovarian carcinosarcoma: a clinicopathological and immunohistochemical analysis of 23 cases. Histopathology, 37(5):427-436.

[2]BoussiosS, KarathanasiA, Zakynthinakis-KyriakouN, et al., 2019. Ovarian carcinosarcoma: current developments and future perspectives. Crit Rev Oncol/Hematol, 134:46-55.

[3]CesconM, GattazzoF, ChenPW, et al., 2015. Collagen VI at a glance. J Cell Sci, 128(19):3525-3531.

[4]ChenPW, CesconM, BonaldoP, 2013. Collagen VI in cancer and its biological mechanisms. Trends Mol Med, 19(7):410-417.

[5]ChenX, ChenSW, YuDS, 2020. Metabolic reprogramming of chemoresistant cancer cells and the potential significance of metabolic regulation in the reversal of cancer chemoresistance. Metabolites, 10(7):289.

[6]CheungA, ShahS, ParkerJ, et al., 2022. Non-epithelial ovarian cancers: how much do we really know? Int J Environ Res Public Health, 19(3):1106.

[7]del CarmenMG, BirrerM, SchorgeJO, 2012. Carcinosarcoma of the ovary: a review of the literature. Gynecol Oncol, 125(1):271-277.

[8]DingSN, ChenXS, ShenKW, 2020. Single-cell RNA sequencing in breast cancer: understanding tumor heterogeneity and paving roads to individualized therapy. Cancer Commun, 40(8):329-344.

[9]GaoCX, ShiJM, ZhangJX, et al., 2022. Chemerin promotes proliferation and migration of ovarian cancer cells by upregulating expression of PD-L1. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(2):164-170.

[10]GeistlingerL, OhS, RamosM, et al., 2020. Multiomic analysis of subtype evolution and heterogeneity in high-grade serous ovarian carcinoma. Cancer Res, 80(20):4335-4345.

[11]GeorgeEM, HerzogTJ, NeugutAI, et al., 2013. Carcinosarcoma of the ovary: natural history, patterns of treatment, and outcome. Gynecol Oncol, 131(1):42-45.

[12]GhoseA, GullapalliSVN, ChohanN, et al., 2022. Applications of proteomics in ovarian cancer: dawn of a new era. Proteomes, 10(2):16.

[13]GotohO, SugiyamaY, TakazawaY, et al., 2019. Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma. Nat Commun, 10:4965.

[14]GuiYR, Aguilar-MahechaA, KrzemienU, et al., 2019. Metastatic breast carcinoma-associated fibroblasts have enhanced protumorigenic properties related to increased IGF2 expression. Clin Cancer Res, 25(23):7229-7242.

[15]HollisRL, CroyI, ChurchmanM, et al., 2022. Ovarian carcinosarcoma is a distinct form of ovarian cancer with poorer survival compared to tubo-ovarian high-grade serous carcinoma. Br J Cancer, 127(6):1034-1042.

[16]KanisMJ, KolevV, GetrajdmanJ, et al., 2016. Carcinosarcoma of the ovary: a single institution experience and review of the literature. Eur J Gynaecol Oncol, 37(1):75-79.

[17]KurmanRJ, ShihIM, 2011. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer—shifting the paradigm. Hum Pathol, 42(7):918-931.

[18]LambMR, GertsenE, MiddlemasE, 2012. Carcinosarcoma of the ovary: case report and literature review. Tenn Med, 105(3):41-42.

[19]LeeHW, ChungW, LeeHO, et al., 2020. Single-cell RNA sequencing reveals the tumor microenvironment and facilitates strategic choices to circumvent treatment failure in a chemorefractory bladder cancer patient. Genome Med, 12:47.

[20]LiangLL, YuJ, LiJ, et al., 2021. Integration of scRNA-seq and bulk RNA-seq to analyse the heterogeneity of ovarian cancer immune cells and establish a molecular risk model. Front Oncol, 11:711020.

[21]LiuC, ZhangY, LiXH, et al., 2022. Ovarian cancer-specific dysregulated genes with prognostic significance: scRNA-seq with bulk RNA-seq data and experimental validation. Ann N Y Acad Sci, 1512(1):154-173.

[22]LiuFS, KohlerMF, MarksJR, et al., 1994. Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in uterine and ovarian sarcomas. Obstet Gynecol, 83(1):118-124.

[23]LuoQK, FuQ, ZhangX, et al., 2020. Application of single-cell RNA sequencing in pancreatic cancer and the endocrine pancreas. In: Yu BW, Zhang JQ, Zeng YM, et al. (Eds.), Single-cell Sequencing and Methylation. Springer, Singapore, p.143-152.

[24]MaXS, GuoJN, LiuKS, et al., 2020. Identification of a distinct luminal subgroup diagnosing and stratifying early stage prostate cancer by tissue-based single-cell RNA sequencing. Mol Cancer, 19:147.

[25]MaynardA, McCoachCE, RotowJK, et al., 2020. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell, 182(5):1232-1251.e22.

[26]MenkeA, PhilippiC, VogelmannR, et al., 2001. Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines. Cancer Res, 61(8):3508-3517.

[27]NäyhäV, StenbäckF, 2008. Angiogenesis and expression of angiogenic agents in uterine and ovarian carcinosarcomas. APMIS, 116(2):107-117.

[28]Rauh-HainJA, GrowdonWB, RodriguezN, et al., 2011. Carcinosarcoma of the ovary: a case-control study. Gynecol Oncol, 121(3):477-481.

[29]Rauh-HainJA, DiverEJ, ClemmerJT, et al., 2013. Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: a SEER analysis. Gynecol Oncol, 131(1):46-51.

[30]RegnerMJ, WisniewskaK, Garcia-RecioS, et al., 2021. A multi-omic single-cell landscape of human gynecologic malignancies. Mol Cell, 81(23):4924-4941.e10.

[31]SiegelRL, MillerKD, JemalA, 2020. Cancer statistics, 2020. CA Cancer J Clin, 70(1):7-30.

[32]ThompsonSL, ComptonDA, 2011. Chromosomes and cancer cells. Chromosome Res, 19(3):433-444.

[33]TongDL, BoocockDJ, DhondalayGKR, et al., 2014. Artificial neural network inference (ANNI): a study on gene-gene interaction for biomarkers in childhood sarcomas. PLoS ONE, 9(7):e102483.

[34]XuJF, FangYF, ChenKL, et al., 2022. Single-cell RNA sequencing reveals the tissue architecture in human high-grade serous ovarian cancer. Clin Cancer Res, 28(16):3590-3602.

[35]YangSX, PhamLK, LiaoCP, et al., 2008. A novel bone morphogenetic protein signaling in heterotypic cell interactions in prostate cancer. Cancer Res, 68(1):198-205.

[36]ZhaoS, XiongW, XuK, 2020. MiR-663a, regulated by lncRNA GAS5, contributes to osteosarcoma development through targeting MYL9. Hum Exp Toxicol, 39(12):1607-1618.

[37]ZhuJ, WenH, JuXZ, et al., 2017. Clinical significance of programmed death ligand-1 and intra-tumoral CD8+ T lymphocytes in ovarian carcinosarcoma. PLoS ONE, 12(1):e0170879.

[38]Zibetti Dal MolinG, AbrahãoCM, ColemanRL, et al., 2018. Response to pembrolizumab in a heavily treated patient with metastatic ovarian carcinosarcoma. Gynecol Oncol Res Pract, 5:6.

[39]ZorzouMP, MarkakiS, RodolakisA, et al., 2005. Clinicopathological features of ovarian carcinosarcomas: a single institution experience. Gynecol Oncol, 96(1):136-142.

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