RESEARCH ARTICLE

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

  • Yue Gao 1,2 ,
  • Chun-Jie Liu 3 ,
  • Hua-Yi Li 1,2 ,
  • Xiao-Ming Xiong 1,2,17 ,
  • Gui-Ling Li 4 ,
  • Sjors G.J.G. In ”t Veld 5,6 ,
  • Guang-Yao Cai 1,2 ,
  • Gui-Yan Xie 3 ,
  • Shao-Qing Zeng 1,2 ,
  • Yuan Wu 1,2 ,
  • Jian-Hua Chi 1,2 ,
  • Jia-Hao Liu 1,2 ,
  • Qiong Zhang 3 ,
  • Xiao-Fei Jiao 1,2 ,
  • Lin-Li Shi 4 ,
  • Wan-Rong Lu 1,2 ,
  • Wei-Guo Lv 7 ,
  • Xing-Sheng Yang 8 ,
  • Jurgen M.J. Piek 9 ,
  • Cornelis D de Kroon 10 ,
  • C.A.R. Lok 11 ,
  • Anna Supernat 12 ,
  • Sylwia Łapińska-Szumczyk 13 ,
  • Anna Łojkowska 13 ,
  • Anna J Żaczek 12 ,
  • Jacek Jassem 14 ,
  • Bakhos A. Tannous 15 ,
  • Nik Sol 5,16 ,
  • Edward Post 5 ,
  • Myron G. Best 5 ,
  • Bei-Hua Kong 8 ,
  • Xing Xie 7 ,
  • Ding Ma 1,2 ,
  • Thomas Wurdinger , 5 ,
  • An-Yuan Guo , 3 ,
  • Qing-Lei Gao , 1,2
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  • 1. Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 2. National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 3. Center for Artificial Intelligence Biology, Hubei Bioinformatics & Molecular Imaging Key Laboratory, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
  • 4. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 5. Department of Neurosurgery, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
  • 6. Brain Tumor Center Amsterdam, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
  • 7. Department of Gynecological Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310011, China
  • 8. Gynecological Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan 250100, China
  • 9. Department of Obstetrics and Gynecology, Catharina Hospital, Michelangelolaan 2, 5623EJ Eindhoven, Eindhoven, The Netherlands
  • 10. Department of Obstetrics and Gynecology, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands
  • 11. Department of Gynecological Oncology, Center of Gynecologic Oncology Amsterdam, Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
  • 12. Laboratory of Translational Oncology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
  • 13. Department of Gynecology, Gynecological Oncology and Gynecological Endocrinology, Medical University of Gdańsk, Gdańsk, Poland
  • 14. Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland
  • 15. Department of Neurology, Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA
  • 16. Department of Neurology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
  • 17. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
t.wurdinger@amsterdamumc.nl
guoay@hust.edu.cn
qingleigao@hotmail.com

Received date: 15 Aug 2022

Accepted date: 19 Oct 2022

Copyright

2022 The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press.

Abstract

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main out-comes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889–0.948), 0.923 (0.855–0.990), 0.918 (0.872–0.963), and 0.887 (0.813–0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889–0.955) in the combined validation cohort; 0.955 (0.912–0.997) in VC1; 0.939 (0.901–0.977) in VC2; 0.917 (0.824–1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Cite this article

Yue Gao , Chun-Jie Liu , Hua-Yi Li , Xiao-Ming Xiong , Gui-Ling Li , Sjors G.J.G. In ”t Veld , Guang-Yao Cai , Gui-Yan Xie , Shao-Qing Zeng , Yuan Wu , Jian-Hua Chi , Jia-Hao Liu , Qiong Zhang , Xiao-Fei Jiao , Lin-Li Shi , Wan-Rong Lu , Wei-Guo Lv , Xing-Sheng Yang , Jurgen M.J. Piek , Cornelis D de Kroon , C.A.R. Lok , Anna Supernat , Sylwia Łapińska-Szumczyk , Anna Łojkowska , Anna J Żaczek , Jacek Jassem , Bakhos A. Tannous , Nik Sol , Edward Post , Myron G. Best , Bei-Hua Kong , Xing Xie , Ding Ma , Thomas Wurdinger , An-Yuan Guo , Qing-Lei Gao . Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study[J]. Protein & Cell, 2023 , 14(8) : 579 -590 . DOI: 10.1093/procel/pwac056

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