Small Extracellular Vesicle-Associated Polymeric Immunoglobulin Receptor in Primary Liver Cancer: From Immunological Mediator to Oncogenic Driver and Biomarker

References

[1] K. Jiang, S. Al-Diffhala, and B. A. Centeno, “Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk Stratification,” Cancer Control 25, no. 1 (2018): 1073274817744625.

[2] I. Tischoff and A. Tannapfel, “Hepatocellular Carcinoma and Cholangiocarcinoma – Different Prognosis, Pathogenesis and Therapy,” Zentralblatt für Chirurgie 132, no. 4 (2007): 300–305.

[3] S. Chidambaranathan-Reghupaty, P. B. Fisher, and D. Sarkar, “Hepatocellular Carcinoma (HCC): Epidemiology, Etiology and Molecular Classification,” Advances in Cancer Research 149 (2021): 1–61.

[4] A. A. Rahnemai-Azar, A. Weisbrod, M. Dillhoff, C. Schmidt, and T. M. Pawlik, “Intrahepatic Cholangiocarcinoma: Molecular Markers for Diagnosis and Prognosis,” Surgical Oncology 26, no. 2 (2017): 125–137.

[5] J. A. Welsh, D. C. I. Goberdhan, L. O'Driscoll, et al., “Minimal Information for Studies of Extracellular Vesicles (MISEV2023): From Basic to Advanced Approaches,” Journal of Extracellular Vesicles 13, no. 2 (2024): e12404.

[6] Y. Lee, J. Ni, J. Beretov, V. C. Wasinger, P. Graham, and Y. Li, “Recent Advances of Small Extracellular Vesicle Biomarkers in Breast Cancer Diagnosis and Prognosis,” Molecular Cancer 22, no. 1 (2023): 33.

[7] C. Wang, X. Zhang, J. Yu, et al., “Spotlights on Extracellular Vesicles in Hepatocellular Carcinoma Diagnosis and Treatment: An Update Review,” Frontiers in Bioengineering and Biotechnology 11 (2023): 1215518.

[8] M. A. Kumar, S. K. Baba, H. Q. Sadida, et al., “Extracellular Vesicles as Tools and Targets in Therapy for Diseases,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 27.

[9] S. K. Tey, S. W. K. Wong, J. Y. T. Chan, et al., “Patient pIgR-Enriched Extracellular Vesicles Drive Cancer Stemness, Tumorigenesis and Metastasis in Hepatocellular Carcinoma,” Journal of Hepatology 76, no. 4 (2022): 883–895.

[10] N. Sphyris and S. A. Mani, “pIgR: Frenemy of Inflammation, EMT, and HCC Progression,” Journal of the National Cancer Institute 103, no. 22 (2011): 1644–1645.

[11] Y. Zhang, J. Zhang, X. Chen, and Z. Yang, “Polymeric Immunoglobulin Receptor (PIGR) Exerts Oncogenic Functions via Activating Ribosome Pathway in Hepatocellular Carcinoma,” International Journal of Medical Sciences 18, no. 2 (2021): 364–371.

[12] S. Qian, Y. He, R. Li, et al., “Polymeric Immunoglobulin Receptor (pIgR) in Cancer Progression: A Critical Role and Potential Therapeutic Target,” Apoptosis 30, no. 7–8 (2025): 1751–1775.

[13] T. Hendrikx, S. Lang, D. Rajcic, et al., “Hepatic pIgR-Mediated Secretion of IgA Limits Bacterial Translocation and Prevents Ethanol-Induced Liver Disease in Mice,” Gut 72, no. 10 (2023): 1959–1970.

[14] Y. Li, T. Y. Li, Q. Qiao, et al., “Polymeric Immunoglobulin Receptor Promotes Th2 Immune Response in the Liver by Increasing Cholangiocytes Derived IL-33: A Diagnostic and Therapeutic Biomarker of Biliary Atresia,” eBioMedicine 108 (2024): 105344.

[15] Y. M. Hong, K. T. Yoon, M. Cho, J. Heo, H. Y. Woo, and W. Lim, “A Case of Small Hepatocellular Carcinoma With an Extensive Lymph Node Metastasis at Diagnosis,” Clinical and Molecular Hepatology 20, no. 3 (2014): 310–312.

[16] N. Adeniji and R. Dhanasekaran, “Current and Emerging Tools for Hepatocellular Carcinoma Surveillance,” Hepatology Communications 5, no. 12 (2021): 1972–1986.

[17] Y. G. Liu, S. T. Jiang, J. W. Zhang, et al., “Role of Extracellular Vesicle-Associated Proteins in the Progression, Diagnosis, and Treatment of Hepatocellular Carcinoma,” Cell & Bioscience 14, no. 1 (2024): 113.

[18] J. Ai, Q. Tang, Y. Wu, et al., “The Role of Polymeric Immunoglobulin Receptor in Inflammation-Induced Tumor Metastasis of Human Hepatocellular Carcinoma,” Journal of the National Cancer Institute 103, no. 22 (2011): 1696–1712.

[19] S. Prasopdee, Y. Yingchutrakul, S. Krobthong, et al., “Differential Plasma Proteomes of the Patients With Opisthorchiasis Viverrini and Cholangiocarcinoma Identify a Polymeric Immunoglobulin Receptor as a Potential Biomarker,” Heliyon 8, no. 10 (2022): e10965.

[20] A. Lapitz, M. Azkargorta, P. Milkiewicz, et al., “Liquid Biopsy-Based Protein Biomarkers for Risk Prediction, Early Diagnosis, and Prognostication of Cholangiocarcinoma,” Journal of Hepatology 79, no. 1 (2023): 93–108.

[21] W. Asanprakit, D. N. Lobo, O. Eremin, and A. J. Bennett, “Expression of Polymeric Immunoglobulin Receptor (PIGR) and the Effect of PIGR Overexpression on Breast Cancer Cells,” Scientific Reports 13, no. 1 (2023): 16606.

[22] L. Gu, J. Chen, Y. Yang, et al., “Data-Independent Acquisition Mass Spectrometry Identification of Extracellular Vesicle Biomarkers for Gastric Adenocarcinoma,” Frontiers in Oncology 12 (2022): 1051450.

[23] D. Li, Y. Gao, C. Wang, and L. Hu, “Proteomic and Phosphoproteomic Profiling of Urinary Small Extracellular Vesicles in Hepatocellular Carcinoma,” Analyst 149, no. 17 (2024): 4378–4387.

[24] J. Wongsuwan, T. Tubtawee, S. Nirattisaikul, et al., “Enhancing Ultrasonographic Detection of Hepatocellular Carcinoma With Artificial Intelligence: Current Applications, Challenges and Future Directions,” BMJ Open Gastroenterology 12, no. 1 (2025): e001832.

[25] A. Arbelaiz, M. Azkargorta, M. Krawczyk, et al., “Serum Extracellular Vesicles Contain Protein Biomarkers for Primary Sclerosing Cholangitis and Cholangiocarcinoma,” Hepatology 66, no. 4 (2017): 1125–1143.

[26] A. Kopystecka, R. Patryn, M. Lesniewska, J. Budzynska, and I. Koziol, “The Use of ctDNA in the Diagnosis and Monitoring of Hepatocellular Carcinoma-Literature Review,” International Journal of Molecular Sciences 24, no. 11 (2023): 9342.

[27] H. Julich-Haertel, S. K. Urban, M. Krawczyk, et al., “Cancer-Associated Circulating Large Extracellular Vesicles in Cholangiocarcinoma and Hepatocellular Carcinoma,” Journal of Hepatology 67, no. 2 (2017): 282–292.

[28] N. D. Parikh, A. S. Mehta, A. G. Singal, T. Block, J. A. Marrero, and A. S. Lok, “Biomarkers for the Early Detection of Hepatocellular Carcinoma,” Cancer Epidemiology, Biomarkers & Prevention 29, no. 12 (2020): 2495–2503.

[29] J. Park, Y. T. Lee, V. G. Agopian, et al., “Liquid Biopsy in Hepatocellular Carcinoma: Challenges, Advances, and Clinical Implications,” Clinical and Molecular Hepatology 31, no. Suppl (2025): S255–S284.

[30] J. Sava, FDA Grants Breakthrough Designation for EvoLiver in HCC (Targetedonc.com, 2025).

Rights & permissions

2026 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.