Investigating VEGF. miR-145-3p, and miR-101-3p Expression in Patients with Cholangiocarcinoma

Document Type : Research Articles


1 Department of Biochemistry and Molecular Biology, Faculty of Medicine of São José do Rio Preto, FAMERP, São José do Rio Preto-SP, Brazil.

2 Department of Gastroenterology, State University of Campinas UNICAMP, Campinas-SP, Brazil.

3 Medical School of the University of Coimbra, Coimbra, Portugal.

4 Biophysics Unit, Faculty of Medicine, University of Coimbra, Polo III - Polo das Ciencias da Saude, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal.

5 Department of Medical Engineering, Coimbra, Portugal.

6 Liver Tumors Study Group (GETF), Sao Jose do Rio Preto Medical School (FAMERP), São José do Rio Preto- SP, Brazil.

7 Department of Pathology, Hospital de Base, Medical School of São José do Rio Preto - HB / FAMERP, Brazil.

8 Department of Pathological Anatomy, Hospital de Clínicas, Universidade Estadual de Campinas - UNICAMP, Brazil.

9 Faculty of Medical Sciences of the State University of Campinas, Campinas, Brazil.


Introduction: Cholangiocarcinoma (CCA) is the second most common type of primary liver cancer. Several factors, such as epigenetic changes in promoter genes, gene expression, and microRNAs (miR), can contribute to genomic instability in cancer. This study aimed at evaluating the expression of VEGF, miRs 145-3p, and 101-3p in patients with CCA and their potential as biomarkers for diagnosis and prognosis of CCA. Material and methods : Sixty two patients were studied. Out of these 62 patients, 41 cases had confirm CCA and 21 cases had hepatopathies complications. The RNA was extracted from a paraffined tissue block, and then the synthesis of cDNA was performed. The analysis of the expression of VEGF, miR-145-3p, and miR-101-3p was carried out by polymerase chain reaction in real time.  Results: The findings revealed that miRs 145-3p and 101-3p were under expressed in the case group compared to the control group (0.46; 0.17; P = 0.0001, respectively). VEGF was overexpressed in the case group compared to the control group (11.8; P = 0.0001). An increase in miR-145-3p expression level was observed in patients with perihilar CCA compared to those with distal CCA (0.51 ± 0.41; 0.17 ± 0.13; P = 0.0698). Survival rate analysis showed that 41.9% of patients with intrahepatic CCA and 31.5% of patients with extrahepatic CCA were free from death within 11 months, leading to a significant difference (P> 0.05). Conclusion: The underexpression of miRNAs, tumor suppressors, the overexpression of VEGF, smoking, and aging were associated with CCA based on our findings. It seems that the reduced expression of the studies miRNAs and increased expression of VEGF can contribute to a decrease in survival rate of patients with tumor in their intrahepatic bile ducts.


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