Ribosomal Proteins in Blood Exosomes as Markers of an Unfavorable Prognosis in Patients with Breast Cancer

Shefer, Aleksei; Babaylova, Elena; Yanshole, Lyudmila; Grygoreva, Alina; Svarovsky, Dmitry; Graifer, Dmitri; Malygin, Alexey; Chernyshovа, Alyona; Tamkovich, Svetlana

doi:10.31557/APJCP.2026.27.7.2497

Ribosomal Proteins in Blood Exosomes as Markers of an Unfavorable Prognosis in Patients with Breast Cancer

Document Type : Research Articles

Authors

¹ Institute of Medicine and Medical Technologies, Novosibirsk State University, Novosibirsk, Russia.

² Knorre Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novovsibirsk, Russia.

³ International Tomography Center, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia.

⁴ Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.

⁵ E.N. Meshalkin National Medical Research Center, Ministry of Health of the Russian Federation, Novosibirsk, Russia.

10.31557/APJCP.2026.27.7.2497

Abstract

Introduction: Exosomes, extracellular vesicles (EVs) 30-150 nm in diameter, are known to mediate intercellular communication by transferring bioactive molecules that can reprogram recipient cell phenotypes. Our analysis of 5-year survival data from breast cancer patients (BCPs) revealed that the poorest outcomes were exclusively associated with conserved signature of three ribosomal proteins (RPs) - MRPL52, RPL28, and RPL40 (UBA52) - that were completely absent in healthy females (HFs) and better-prognosis cases. Strikingly, all patients with this exosomal RP profile succumbed to metastatic relapse within the observation period. Methods: While RPs are known components of tumor-derived exosomes, their absence in EVs from normal cells suggests cancer-specific sorting mechanisms. To investigate this, we characterized exosomal RP cargo from three breast cancer cell lines (MCF-7, BT-474, BT-549), finding cell-type-specific RP patterns that differed from the clinical BC signature. Transfection of BT-549 cells with FLAG-tagged RPS3 (an aggressive cancer-associated RP) induced dramatic changes in exosomal RP composition, including the appearance of RPL28 - matching our clinical findings. Results: Bioinformatic analysis revealed that the RPs identified in BCP blood exosomes (MRPL52, RPL28, RPL40, RPS6) are associated with poor prognosis across multiple cancers and participate in key oncogenic pathways. Conclusion: The concordance between our clinical and experimental data suggests that: (a) specific RPs are selectively packaged into exosomes under stress conditions; (b) this process may contribute to BC aggressiveness; (c) exosomal RP profiling could serve as a novel prognostic approach. These findings illuminate previously unrecognized roles of ribosomal components in cancer progression through EV-mediated communication.

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