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Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer

  • Authors:
    • Tonghui Bao
    • Xiaoping Li
    • Wufen Li
    • Rui Yang
    • Youhong Ye
    • Wenjia Zhang
    • Lin Qi
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, Affiliated Hospital of Qinghai University, Xining, Qinghai 810000, P.R. China, Department of Geriatrics, Affiliated Hospital of Qinghai University, Xining, Qinghai 810000, P.R. China, Department of Hematology and Oncology, Qinghai Provincial Traditional Chinese Medicine Hospital, Xining, Qinghai 810000, P.R. China, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710000, P.R. China, Department of Gynecology, Affiliated Hospital of Qinghai University, Xining, Qinghai 810000, P.R. China, Department of Oncology and Gynecology, Affiliated Hospital of Qinghai University, Xining, Qinghai 810000, P.R. China
    Copyright: © Bao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 13
    |
    Published online on: December 31, 2025
       https://doi.org/10.3892/mco.2025.2922
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Abstract

Cervical cancer (CC) is a malignancy characterized by persistent human papillomavirus (HPV) infection, immune evasion and tumor microenvironment remodeling. Due to its high invasiveness and drug resistance, effective diagnosis and treatment remain challenging. The present study employed multi‑omics analysis to explore the molecular characteristics of plasma extracellular vesicles (EVs) in CC. EVs were isolated from the plasma of 3 patients with CC and 3 healthy controls via ultracentrifugation, and validated by nanoparticle tracking analysis, transmission electron microscopy and western blotting. MicroRNA (miRNA or miR) sequencing identified 22 differentially expressed miRNAs, the target genes of which were enriched in HPV infection, p53, PI3K‑Akt and Wnt signaling pathways. Proteomic analysis revealed 49 differentially expressed proteins associated with complement activation, cholesterol metabolism and coagulation. Integrated analysis highlighted key miRNA‑protein interaction networks, identifying hsa‑miR‑1‑3p and LRP1 as potential diagnostic biomarkers, and their differential expression was further confirmed by reverse transcription‑quantitative PCR. These findings provide novel insights into the role of EVs in CC pathogenesis and offer promising potential targets for early diagnosis and therapeutic intervention.
View Figures

Figure 1

Isolation and characterization of
plasma-derived EVs from patients with CC and HC. (A) Overall
experimental design for CC plasma EV isolation. (B) Workflow of
analytical strategies for miRNA sequencing, proteomics and
multi-omics integration. (C) Nanoparticle tracking analysis
revealed the size distribution of plasma EV. (D) Transmission of EV
electron microscopy images. (E) Western blot validation of EV
markers. EVs, extracellular vesicles; CC, cervical cancer; HC,
healthy controls; miR or miRNA, microRNA; LC-MS, Liquid
chromatography-mass spectrometry.

Figure 2

Differential expression and
functional enrichment analysis of extracellular vesicle-derived
miRNAs in CC. (A) Volcano plot showing DEMs between patients with
CC and HC. (B) Heatmap and corresponding bar chart of DEMs in CC
and HC groups. (C) KEGG pathway enrichment analysis of predicted
target genes of DEMs. (D) GO enrichment analysis of DEMs target
genes. miR or miRNA, microRNA; CC, cervical cancer; DEMs,
differentially expressed miRNAs; HC, healthy controls; KEGG, Kyoto
Encyclopedia of Genes and Genomes; GO, Gene Ontology.

Figure 3

Proteomic profiling and functional
enrichment analysis of plasma-derived extracellular vesicles in CC.
(A) Volcano plot of DEPs between HC and patients with CC. (B)
Heatmap and corresponding bar plot of DEPs in CC and HC groups. (C)
Tissue and organ distribution of EV-derived DEPs. (D) KEGG pathway
enrichment analysis of DEPs. (E) GO pathway enrichment analysis of
DEPs. CC, cervical cancer; DEPs, differentially expressed proteins;
HC, healthy controls; KEGG, Kyoto Encyclopedia of Genes and
Genomes; GO, Gene Ontology.

Figure 4

Integrated analysis of EV-derived
miRNA and proteomic data reveals a key hsa-miR-1-3p-LRP1 regulatory
axis in CC. (A) Heatmap showing Spearman correlation between
differentially expressed miRNAs and proteins (red: positive
correlation; blue: negative correlation). (B) Differential miRNA
target gene enrichment pathway and differential protein enrichment
pathway and their shared metabolic pathways. (C) Protein-protein
interaction network of DEPs. (D) Interaction network map of
differentially expressed miRNAs and DEPs. (E) Tissue-specific
expression profile of LRP1. (F) Reverse transcription-quantitative
PCR validation of EV-derived hsa-miR-1-3p (left) and LRP1 (right)
expression levels in HC and patients with CC (n=3)
*P<0.05 and **P<0.01. EV, extracellular
vesicle; miR or miRNA, microRNA; CC, cervical cancer; DEPs,
differentially expressed proteins; HC, healthy controls; KEGG,
Kyoto Encyclopedia of Genes and Genomes.
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Copy and paste a formatted citation
Spandidos Publications style
Bao T, Li X, Li W, Yang R, Ye Y, Zhang W and Qi L: Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer. Mol Clin Oncol 24: 13, 2026.
APA
Bao, T., Li, X., Li, W., Yang, R., Ye, Y., Zhang, W., & Qi, L. (2026). Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer. Molecular and Clinical Oncology, 24, 13. https://doi.org/10.3892/mco.2025.2922
MLA
Bao, T., Li, X., Li, W., Yang, R., Ye, Y., Zhang, W., Qi, L."Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer". Molecular and Clinical Oncology 24.2 (2026): 13.
Chicago
Bao, T., Li, X., Li, W., Yang, R., Ye, Y., Zhang, W., Qi, L."Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer". Molecular and Clinical Oncology 24, no. 2 (2026): 13. https://doi.org/10.3892/mco.2025.2922
Copy and paste a formatted citation
x
Spandidos Publications style
Bao T, Li X, Li W, Yang R, Ye Y, Zhang W and Qi L: Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer. Mol Clin Oncol 24: 13, 2026.
APA
Bao, T., Li, X., Li, W., Yang, R., Ye, Y., Zhang, W., & Qi, L. (2026). Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer. Molecular and Clinical Oncology, 24, 13. https://doi.org/10.3892/mco.2025.2922
MLA
Bao, T., Li, X., Li, W., Yang, R., Ye, Y., Zhang, W., Qi, L."Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer". Molecular and Clinical Oncology 24.2 (2026): 13.
Chicago
Bao, T., Li, X., Li, W., Yang, R., Ye, Y., Zhang, W., Qi, L."Integrated multi‑omics profiling of plasma extracellular vesicles reveals the hsa‑miR‑1‑3p‑LRP1 axis as a potential biomarker in cervical cancer". Molecular and Clinical Oncology 24, no. 2 (2026): 13. https://doi.org/10.3892/mco.2025.2922
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