The Abnormal Expression of miR-205-5p, miR-195-5p, and VEGF-A in Human Cervical Cancer Is Related to the Treatment of Venous Thromboembolism

Biomed Res Int. 2020 Aug 8:2020:3929435. doi: 10.1155/2020/3929435. eCollection 2020.

Abstract

Background: Low molecular heparin (LWMH) therapy can prevent the occurrence of VTE in tumor patients and may have a direct antitumor effect. However, the expression pattern of VEGF-A and microRNAs was less reported in cervical cancer subjects who received concurrent chemoradiotherapy (CCRT) or received anticoagulant treatment with low molecular weight heparin (LWMH) after CCRT (CCRT+LWMH).

Methods: In this study, 30 cervical cancer subjects treated with CCRT and 30 cervical cancer patients treated with CCRT+LWMH were enrolled. We screened five miRNAs (miR-15a-5p, miR-16-5p, miR-29a-3p, miR-195-5p, and miR-205-5p), which have multiple binding sites with VEGF-A and are highly expressed in serum of patients with cervical cancer, by RT-qPCR. The expression level of VEGF-A was also detected by RT-qPCR and ELISA. Statistical methods were used for difference and correlation analyses.

Results: We observed the curative effect in the two treatment methods. In the CCRT group, the total effective rate was 60.00%, and in the CCRT+LWMT group, the total effective rate was 83.33% (P = 0.013, χ 2 = 6.129). Additionally, the serum levels of VEGF-A in the CCRT+LWMH group were downregulated, relative to the CCRT group (P < 0.05), and VEGF-A in serum was significantly positively correlated with venous thromboembolism (VTE) (r = 2.134, P = 0.035). Only miR-205-5p and miR-195-5p were upregulated in CCRT+LWMH, relative to CCRT (P < 0.05). In serum of patients with cervical cancer after CCRT+LWMH treatment, there was no significant correlation between VEGF-A and miR-15a-5p (r = -0.132, P = 0.209), miR-16-5p (r = -0.205, P = 0.311), or miR-29a-3p (r = -0.029, P = 0.662), but VEGF-A was significantly negatively correlated with miR-195-5p (r = -0.396, P = 0.040) and miR-205-5p (r = -0.315, P = 0.032). Furthermore, VTE was also significantly negatively correlated with miR-195-5p (r = -0.412, P = 0.031) and miR-205-5p (r = -0.123, P = 0.044).

Conclusion: These data revealed roles for VEGF-A and these miRNAs as potential biomarkers in cervical cancer patients with VTE, which exhibited usage potential in the treatment of venous thromboembolism.

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Cell Line, Tumor
  • Chemoradiotherapy
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Heparin / administration & dosage
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Uterine Cervical Neoplasms / complications
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / genetics*
  • Venous Thromboembolism / complications
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / genetics
  • Venous Thromboembolism / pathology

Substances

  • Anticoagulants
  • MIRN195 microRNA, human
  • MIRN205 microRNA, human
  • MicroRNAs
  • Vascular Endothelial Growth Factor A
  • Heparin