Plasma extracellular vesicle long RNA profiling identifies a diagnostic signature for the detection of pancreatic ductal adenocarcinoma.
Shulin Yu, Yuchen Li, Zhuan Liao, Zheng Wang, Zhen Wang, Yan Li, Ling Qian, Jingjing Zhao, Huajie Zong, Bin Kang, Wen-Bin Zou, Kun Chen, Xianghuo He, Zhiqiang Meng, Zhen Chen, Shenglin Huang, Peng Wang
Author Information
- Shulin Yu: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
- Yuchen Li: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Zhuan Liao: Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, the Second Military Medical University, Shanghai, China. ORCID
- Zheng Wang: Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China. ORCID
- Zhen Wang: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Yan Li: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Ling Qian: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
- Jingjing Zhao: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Huajie Zong: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Bin Kang: Fudan University Shanghai Cancer Center - InstitutMerieux Laboratory, Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
- Wen-Bin Zou: Department of Gastroenterology, Digestive Endoscopy Center, Changhai Hospital, the Second Military Medical University, Shanghai, China.
- Kun Chen: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
- Xianghuo He: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. ORCID
- Zhiqiang Meng: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
- Zhen Chen: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China wangp413@163.com slhuang@fudan.edu.cn zchenzl@fudan.edu.cn.
- Shenglin Huang: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China wangp413@163.com slhuang@fudan.edu.cn zchenzl@fudan.edu.cn. ORCID
- Peng Wang: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China wangp413@163.com slhuang@fudan.edu.cn zchenzl@fudan.edu.cn. ORCID
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.
Adolescent
Adult
Aged
Aged, 80 and over
Alpha-Globulins
Area Under Curve
CA-19-9 Antigen
Carcinoma, Pancreatic Ductal
Case-Control Studies
Child
Claudin-1
Extracellular Vesicles
Female
Fibrinogen
Humans
Keratin-19
Male
Membrane Proteins
Middle Aged
Myelin and Lymphocyte-Associated Proteolipid Proteins
Pancreatic Neoplasms
Pancreatitis, Chronic
RNA
RNA, Circular
RNA, Long Noncoding
RNA, Messenger
ROC Curve
Sequence Analysis, RNA
Support Vector Machine
Tissue Inhibitor of Metalloproteinase-1
Ubiquitin-Protein Ligases
Young Adult
Alpha-Globulins
CA-19-9 Antigen
CLDN1 protein, human
Claudin-1
FGA protein, human
KRT19 protein, human
Keratin-19
MAL2 protein, human
Membrane Proteins
Myelin and Lymphocyte-Associated Proteolipid Proteins
RNA, Circular
RNA, Long Noncoding
RNA, Messenger
TIMP1 protein, human
Tissue Inhibitor of Metalloproteinase-1
inter-alpha-inhibitor
RNA
Fibrinogen
MARCHF2 protein, human
Ubiquitin-Protein Ligases
