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Molecular Diagnostics

Transcriptomic profiling of blood platelets identifies a diagnostic signature for pancreatic cancer

British Journal of Cancer volume 132, pages 937–946 (2025)Cite this article

Subjects

Abstract

Background

Pancreatic cancer (PaCa) is a deadly malignancy that is often diagnosed at an advanced stage, limiting treatment and reducing survival. There is an urgent need for convenient and accurate diagnostic markers for the early detection of PaCa.

Methods

In this multicenter case-control study, we performed transcriptome analysis of 673 platelet samples from different in-house and public cohorts. RNA sequencing and RT-qPCR were used to discover and validate potential platelet biomarkers. A multi-gene signature was developed using binomial generalized linear model and independently validated in multicenter cohorts.

Results

Two platelet RNAs, SCN1B and MAGOHB, consistently showed robust altered expression patterns between PaCa and healthy controls across cohorts, as confirmed by both RNA sequencing and RT-qPCR. The diagnostic two-RNA signature, PLA2Sig, demonstrated remarkable performance in detecting PaCa, with area under the receiver operating characteristic curve (AUC) values of 0.808, 0.900, 0.783, and 0.830 across multicenter cohorts. Furthermore, PLA2Sig effectively identified resectable stage I&II PaCa cases with an AUC of 0.812. Notably, PLA2Sig outperformed the traditional serum markers carcinoembryonic antigen and carbohydrate antigen 19-9 in distinguishing PaCa from healthy controls, and is complementary to established blood-based screening biomarkers.

Conclusion

These findings provide preliminary but promising evidence for the potential utility of platelet RNAs as an alternative non-invasive liquid biopsy tool for the early detection of PaCa.

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Fig. 1: Platelet transcriptome alterations in pancreatic cancer.
Fig. 2: Identification and validation of platelet biomarkers for pancreatic cancer.
Fig. 3: Development and performance evaluation of PLA2Sig in PaCa risk assessment.
Fig. 4: Early detection of PaCa by PLA2Sig in the pooled cohort.
Fig. 5: Optimization of PaCa detection by combining PLA2Sig with conventional tumor markers.
Fig. 6: Evaluation of diagnostic potential using decision curve analysis and calibration curve analysis.

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Data availability

Raw RNA-seq data generated during this study has been deposited in the Genome Sequence Archive in the National Genomics Data Center [58], China National Center for Bioinformation [59] (https://ngdc.cncb.ac.cn/?lang=en, HRA006016). The raw sequencing data are subject to restricted access in accordance with data privacy laws. All public bulk RNA sequencing data are available from the GEO database under accession numbers GSE183635 and GSE68086.

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Funding

This study was supported by the Natural Science Foundation of Zhejiang Province (No. LTGY23H030003), Wenzhou Science and Technology Project (No. Y20210174), Medical Special Fund of Changhai Hospital (No.2020SLZ005). The funders had no roles in study design, data collection and analysis, publication decision, or manuscript preparation.

Author information

Author notes

  1. These authors contributed equally: Weiping Ji, Yichun Xiong, Wei Yang.

Authors and Affiliations

  1. Department of General Surgery, School of Biomedical Engineering, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

    Weiping Ji, Yichun Xiong, Jianzhong Su & Meng Zhou

  2. Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China

    Weiping Ji & Xiaoling Guo

  3. Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230001, China

    Wei Yang

  4. Department of General Surgery, Shanghai Changhai Hospital of Navy Medical University, Shanghai, 200438, China

    Zhuo Shao & Gang Jin

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  1. Weiping Ji
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Contributions

MZ and JS contributed to conception and design; YX and WJ contributed to data analysis and interpretation. WJ, WY, ZS, XG and GJ contributed to the provision of study materials or patients and experiments. WJ, YX and MZ drafted the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Jianzhong Su or Meng Zhou.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Ethics Committees of Shanghai Changhai Hospital (approval number: CHEC2017-088) and the Second Affiliated Hospital of Wenzhou Medical University (approval number: 2017-046), and informed consent was obtained from all participants in accordance with the Declaration of Helsinki.

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Ji, W., Xiong, Y., Yang, W. et al. Transcriptomic profiling of blood platelets identifies a diagnostic signature for pancreatic cancer. Br J Cancer 132, 937–946 (2025). https://doi.org/10.1038/s41416-025-02980-z

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