The expression of GLUT-1 and VEGF-A mRNA in the rectal cancer patients with neoadjuvant chemoradiation

Abstract

Latar belakang: Angka kekambuhan dan resistensi pasien kanker rektum mencapai 40 persen. Kondisi tersebut bisa disebabkan karena peningkatan ekspresi GLUT-1 dan VEGF-A, serta mempengaruhi prognosis pasien. Tujuan penelitian ini adalah untuk mengetahui korelasi ekspresi mRNA GLUT-1 dan VEGF-A, serta hubungannya dengan prognosis pasien kanker rektum yang menjalani kemoradiasi.

Metode: Penelitian Kohor ini melibatkan 16 orang pasien kanker rektum lokal stadium II atau III yang menjalani kemoradiasi di RSUP Kariadi Semarang. Sampel darah intravena diambil 5 mL pada saat sebelum dan sesudah kemoradiasi. Total RNA diisolasi dari 200 μl serum, kemudian dilakukan sintesis cDNA. Ekspresi mRNA GLUT-1 dan VEGF-A dikuantifikasi dengan metode Livak menggunakan reference gene β-actin.

Hasil: Rata-rata ekspresi mRNA GLUT-1 menurun signifikan 2,14 kali (P=0,044) dan mRNA VEGF-A menurun 1,9 kali (P = 0,03). Ekspresi mRNA GLUT-1 dan VEGF-A berkorelasi positif kuat dan signifikan pada saat sebelum (r = 0,6; R2 = 0,455; P = 0,013) dan sesudah kemoradiasi (r = 0,8; R2 = 0,598; P < 0,001). Peningkatan ekspresi mRNA GLUT-1 berhubungan dengan prognosis buruk pasien, dengan resiko 18 kali lebih tinggi (P=0,036; OR=18, 95% CI=1,2 – 261). Peningkatan ekspresi mRNA VEGF-A tidak berhubungan signifikan dengan prognosis pasien (P=0,12; OR=9; 95%CI=0,6-123).

Kesimpulan: Ekspresi mRNA GLUT-1 dan VEGF-A berkorelasi positif dan saling mempengaruhi satu dengan lainnya. Peningkatan ekspresi mRNA GLUT-1 berhubungan dengan prognosis buruk pasien. Hasil penelitian ini mengindikasikan bahwa ekspresi mRNA GLUT-1 dari sampel darah berpotensi sebagai biomarker prognosis pada pasien kanker rektum yang menjalani kemoradiasi.

Kata kunci: kanker rektum, kemoradiasi, GLUT-1, VEGF-A, prognosis

Abstract

Background: Rectal cancer patients have 40 percent risk of recurrence and resistance, which is triggered by increasing in GLUT-1 and VEGF-A mRNA expression. This condition associate with the patients prognosis. This study aimed to determine the correlation between GLUT-1 and VEGF-A mRNA expression, and analyze its association with the rectal cancer patients prognosis who received chemoradiation.

Methods: This was a Cohort study involving 16 rectal cancer patients with stage II or III undergoing chemoradiation at Kariadi Hospital Semarang. Five milliliters of intravenous blood samples were taken before and after chemoradiation. Total RNA was isolated from 200 μl of blood serum, followed by cDNA synthesis. GLUT-1 and VEGF-A mRNA expression was quantified by the Livak method using β-actin as a reference gene.

Results: GLUT-1 and VEGF-A mRNA expression decreased significantly 2.14 times (P=0,044) and 1,9 times (P=0,03), respectively. Expression of GLUT-1 and VEGF-A mRNA have a significant and strong positive correlation at before (r=0,6; R2=0,455; P=0,013) and after chemoradiation (r=0,8; R2=0,598; P<0,001). GLUT-1 mRNA expression enhancement significantly associate with poor prognosis and risk 18 times of worse prognosis (P=0,036; OR=18, 95% CI=1,2–261). VEGF-A mRNA expression did not associate with patient prognosis (P=0,12; OR=9; 95%CI=0,6-123).

Conclusion: Expression of GLUT-1 and VEGF-A mRNA have a significant and strong positive correlation. GLUT-1 mRNA expression enhancement significantly associate with the poor prognosis of the rectal cancer patients. Our finding suggests that GLUT-1 mRNA expression from blood sample was potential as a biomarker to predict rectal cancer patient prognosis who received chemoradiation

Keywords: rectal cancer, chemoradiotherapy, GLUT-1, VEGF-A, prognosis