EKSPRESI miR-200c dan mRNA VEGF-A (VASCULAR ENDOTHELIAL GROWTH FACTOR A) PADA PLASMA PASIEN KARSINOMA HEPATOSELULER

NANDA QORIANSAS, Prof. dr. Sofia Mubarika H., M.Med.Sc., Ph.D.; dr. Didik Setyo Heriyanto, Ph.D., Sp.PA .

2017 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar belakang: Karsinoma hepatoseluler (KHS) adalah salah satu keganasan pada hati utama yang secara signifikan mengancam kesehatan manusia di dunia, termasuk Indonesia. Karsinoma hepatoseluler terutama pada laki-laki, dengan tingkat rata-rata mortalitas tertinggi ke-2 di dunia. Perkembangan KHS diduga melibatkan perubahan regulasi gen yang penting dalam proses seluler. Salah satu regulator tingkat molekuler yang banyak dilaporkan berperan dalam hepatokarsinogenesis adalah mikro-RNA. Beberapa penelitian sebelumnya menyebutkan Ekspresi miRNA-200c diketahui mengalami penurunan ekspresi pada jaringan dan sel lini KHS. Penurunan ekspresi miRNA-200c pada jaringan kanker berhubungan dengan rendahnya harapan hidup penderita KHS. Sel kanker memproduksi protein angiogenik, yaitu Vascular Endothelial Growth Factor A (VEGF-A) merupakan golongan protein growth factor yang berperan dalam angiogenesis sel kanker. Penelitian ini dilakukan untuk mengetahui apakah terdapat perbedaan ekspresi miRNA-200c dan mRNA VEGF-A pada plasma penderita KHS dan kontrol individu sehat. Tujuan: Penelitian ini bertujuan untuk melakukan kuantifikasi dan membandingkan ekspresi miR-200c dan mRNA VEGF-A pada plasma darah pasien karsinoma hepatoseluler dan individu sehat. Hasil: Ekspresi miR-200c pada plasma darah pasien KHS mengalami penurunan ekspresi sebesar 1,85 kali lipat dibandingkan pada plasma darah individu sehat. Ekspresi mRNA VEGF-A pada plasma darah pasien KHS mengalami peningkatan 4,42 kali lipat dibanding ekspresinya pada plasma darah individu sehat (p<0,001). Ekspresi relatif miR-200c berkorelasi negatif dengan ekspresi mRNA VEGF-A plasma darah pasien KHS . Kesimpulan: Ekspresi miR-200c dan mRNA-VEGF-A pada plasma darah pasien KHS berbeda dengan individu sehat. Terdapat korelasi antara ekspresi miR-200c dan mRNA-VEGF-A pada plasma darah pasien KHS.

Background : Hepatocellular carcinoma (HCC) is one of the major liver malignancies that significantly threatens human health worldwide, including Indonesia. Hepatocellular carcinoma is predominantly in males, with the second highest rate of mortality in the world. One of the molecular-level regulators reported to play a important role in hepatocarcinogenesis is microRNA. Previous studies found that miRNA-200c expression is significantly downregulated HCC tissue and HCC cell. Decreased of miRNA-200c expression in cancer tissue is associated with lower survival rate HCC patients. Cancer cell produce angiogenic proteins, Vascular Endothelial Growth Factor-A (VEGF-A). VEGF-A is a class of growth factors that play a important role in the angiogenesis of cancer tissue. This study was conducted to determine whether there is a difference in the expression of miRNA-200c and mRNAVEGF-A in blood plasma of HCC patients and healthy subjects. Objective : The aim of this study is to quantify and compare the expression of miRNA-200c and mRNA VEGF-A in blood plasma between HCC patients and healthy subjects. Methods : Observational analytic with cross-sectional study using blood plasma samples from 36 HCC patients and 36 healthy subjects. The relative expression of miRNA-200c and mRNA VEGF-A was quantified using reverse transcription Real Time Quantitative PCR (qRT PCR). method was used to calculate the relative quantification of miRNA-200c expression and mRNA VEGF-A expression. The statistical test was used unpaired t-test to compare the expression of miRNA-200c and mRNA VEGF-A between plasma of HCC patients and healthy subjects, whereas Pearson correlation test was used to find out the correlation between miRNA-200c expression and mRNA VEGF-A expression in blood plasma. Results : Expression of miRNA-200c in blood plasma of HCC patients downregulated 1.85-fold compared to its expression in healthy subject. Expression of mRNA VEGF-A in blood plasma of HCC patients upregulated 4.42-fold compared to its expression in healthy subjects (p <0.001). The relative expression of miRNA-200c is negatively correlated with relative expression of mRNA VEGF-A in the blood plasma of HCC patients. Conclusion : The expression of miRNA-200c and mRNA VEGF-A in blood plasma of HCC patients is different from healthy subjects. There is a negative correlation between the expression of miRNA-200c and mRNA VEGF-A in the blood plasma of HCC patients.

Kata Kunci : Plasma, Karsinoma hepatoseluler, miR-200c, mRNA VEGF, Blood Plasma, Hepatocellular carcinoma