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Original article
Plasma extracellular vesicle long RNA profiling identifies a diagnostic signature for the detection of pancreatic ductal adenocarcinoma
  1. Shulin Yu1,2,
  2. Yuchen Li2,3,
  3. Zhuan Liao4,
  4. Zheng Wang5,
  5. Zhen Wang2,3,
  6. Yan Li2,3,
  7. Ling Qian1,2,
  8. Jingjing Zhao2,3,
  9. Huajie Zong2,6,
  10. Bin Kang7,
  11. Wen-Bin Zou4,
  12. Kun Chen1,2,
  13. Xianghuo He2,3,
  14. Zhiqiang Meng1,2,
  15. Zhen Chen1,2,
  16. Shenglin Huang2,3,
  17. Peng Wang1,2
  1. 1 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
  2. 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
  3. 3 Fudan University Shanghai Cancer Center, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
  4. 4 Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, the Second Military Medical University, Shanghai, China
  5. 5 Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, China
  6. 6 Department of General Surgery, Huashan Hospital, Fudan University, Fudan University, Shanghai, China
  7. 7 Fudan University Shanghai Cancer Center - InstitutMerieux Laboratory, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China
  1. Correspondence to Dr Peng Wang, Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; wangp413{at}163.com; Professor Shenglin Huang, Fudan University Shanghai Cancer Center, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Shanghai, China; slhuang{at}fudan.edu.cn; Dr Zhen Chen, Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; zchenzl{at}fudan.edu.cn

Abstract

Objective Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose at resectable stage. Recent studies have suggested that extracellular vesicles (EVs) contain long RNAs. The aim of this study was to develop a diagnostic (d-)signature for the detection of PDAC based on EV long RNA (exLR) profiling.

Design We conducted a case-control study with 501 participants, including 284 patients with PDAC, 100 patients with chronic pancreatitis (CP) and 117 healthy subjects. The exLR profile of plasma samples was analysed by exLR sequencing. The d-signature was identified using a support vector machine algorithm and a training cohort (n=188) and was validated using an internal validation cohort (n=135) and an external validation cohort (n=178).

Results We developed a d-signature that comprised eight exLRs, including FGA, KRT19, HIST1H2BK, ITIH2, MARCH2, CLDN1, MAL2 and TIMP1, for PDAC detection. The d-signature showed high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.960, 0.950 and 0.936 in the training, internal validation and external validation cohort, respectively. The d-signature was able to identify resectable stage I/II cancer with an AUC of 0.949 in the combined three cohorts. In addition, the d-signature showed superior performance to carbohydrate antigen 19-9 in distinguishing PDAC from CP (AUC 0.931 vs 0.873, p=0.028).

Conclusion This study is the first to characterise the plasma exLR profile in PDAC and to report an exLR signature for the detection of pancreatic cancer. This signature may improve the prognosis of patients who would have otherwise missed the curative treatment window.

  • extracellular vesicle
  • long RNA
  • pancreatic ductal adenocarcinoma
  • diagnosis
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Footnotes

  • SY, YL, ZL and ZW are joint first authors.

  • Contributors PW, SH and ZC contributed to conception and design; SY, YL, ZL, ZhengW, ZhenW, YL, LQ, W-BZ and ZM contributed to provision of study materials or patients; SY, YL, ZL, ZhenW, YL, LQ, ZJ, HZ, W-BZ, KC and ZM collected and assembled the data. PW, SH, ZC, SY, YL and BK contributed to data analysis and interpretation. PW, SH, ZC, SY and YL wrote the manuscript. All authors finally approved the manuscript.

  • Funding This study was supported by the National Natural Science Foundation of China (81622049, 81672779, 81871989); the Shanghai Science and Technology Committee Programme (19XD1420900); Shanghai Education Commission Programme (17SG04) and Shanghai Municipal Commission of Health and Family Planning (201540191).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the Ethics Committee of the Fudan University Shanghai Cancer Center, Shanghai, China (approval no: 050432-4-1212B), and written informed consent was obtained from each participant in accordance with institutional guidelines.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement The RNA-Seq data have been deposited at the Gene Expression Omnibus (GEO) under the accession number GSE133684.

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