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. 2022 Jul 1;23(7):2233-2241.
doi: 10.31557/APJCP.2022.23.7.2233.

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

Maria Clara Jessica Calastri  1 , Rafael Fernandes Ferreira  2 , Graciele Domitila Tenani  1 , Lucas Poleto Spinola  1 , Gabriel Feltrin Vieira  1 , Maria Filomena Rabaça Roque Botelho  3 , Ana Margarida Coelho Abrantes  4 , José Guilherme Lopes Rodrigues Tralhão  3 , Ana Filipa Marques De Brito  5 , Renato Ferreira Da Silva  1   6 , Rita De Cassia Martins Alves Da Silva  1   6 , Eliane Milharcix Zanovelo  7 , Larissa Bastos Eloy Da Costa  8 , Daniele Caroline Brito De Souza  7 , Dalisio De Santi Neto  1   7 , Ilka De Fatima Santana Ferreira Boin  9 , Doroteia Rossi Silva Souza  1
Affiliations

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

Maria Clara Jessica Calastri et al. Asian Pac J Cancer Prev. .

Abstract

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.

Keywords: Bile Duct Diseases; Gene expression; MicroRNAs; Molecular biology.

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Conflict of interest statement

The authors declared that there is no conflict of interest regarding the publication of this article.

Figures

Figure 1
Figure 1
Relative Expression of miR-145-3p and miR-101-3p (mean value of 2-ddCt) in Patients with Cholangiocarcinoma (CCA) and Individuals without the Disease (CG)
Figure 2
Figure 2
Receiver Operator Characteristic (ROC) Curve of the Levels of Relative Expression of miR-145-3p and miR-101-3p Considering Patients with Intrahepatic, Perihilar and Distal Cholangiocarcinoma (CCA)
Figure 3
Figure 3
Actuarial Kaplan-Meier Curve Regarding Event-Free Survival Analysis of Patients with CholangiocarciNoma. Actuarial Kaplan-Meier Curve; Log Rank Test, with significance level of <0.05
Figure 4
Figure 4
Kaplan-Meier Actuarial Curve regarding Survival Analysis Related to the Expression of miR-145-3p, miR-101-3p, and VEGF in Patients with Cholangiocarcinoma
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