Single-cell transcriptome profiles the heterogeneity of tumor cells and microenvironments for different pathological endometrial cancer and identifies specific sensitive drugs.
Fang Ren, Lingfang Wang, Yuyouye Wang, Jiaxuan Wang, Yuanpei Wang, Xiaole Song, Gong Zhang, Fangfang Nie, Shitong Lin
Author Information
Fang Ren: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. renfang@foxmail.com. ORCID
Lingfang Wang: Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yuyouye Wang: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Jiaxuan Wang: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Yuanpei Wang: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Xiaole Song: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Gong Zhang: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Fangfang Nie: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Shitong Lin: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 1131108208@qq.com.
Endometrial cancer (EC) is a highly heterogeneous malignancy characterized by varied pathology and prognoses, and the heterogeneity of its cancer cells and the tumor microenvironment (TME) remains poorly understood. We conducted single-cell RNA sequencing (scRNA-seq) on 18 EC samples, encompassing various pathological types to delineate their specific unique transcriptional landscapes. Cancer cells from diverse pathological sources displayed distinct hallmarks labeled as immune-modulating, proliferation-modulating, and metabolism-modulating cancer cells in uterine clear cell carcinomas (UCCC), well-differentiated endometrioid endometrial carcinomas (EEC-I), and uterine serous carcinomas (USC), respectively. Cancer cells from the UCCC exhibited the greatest heterogeneity. We also identified potential effective drugs and confirmed their effectiveness using patient-derived EC organoids for each pathological group. Regarding the TME, we observed that prognostically favorable CD8 Tcyto and NK cells were prominent in normal endometrium, whereas CD4 Treg, CD4 Tex, and CD8 Tex cells dominated the tumors. CXCL3 macrophages associated with M2 signature and angiogenesis were exclusively found in tumors. Prognostically relevant epithelium-specific cancer-associated fibroblasts (eCAFs) and SOD2 inflammatory CAFs (iCAFs) predominated in EEC-I and UCCC groups, respectively. We also validated the oncogenic effects of SOD2 iCAFs in vitro. Our comprehensive study has yielded deeper insights into the pathogenesis of EC, potentially facilitating personalized treatments for its varied pathological types.
References
Cell. 2021 Jun 24;184(13):3573-3587.e29
[PMID: 34062119]
J Clin Oncol. 2020 Jan 1;38(1):1-10
[PMID: 31682550]
