Increasing serum miR-124-3p expression is associated with the high survival rate of a rectal cancer patient after neoadjuvant chemoradiotherapy
Abstract
Latar Belakang: Kanker kolorektal menempati urutan ketiga penyebab kanker di dunia, dengan prevalensi kanker rektum sebanyak 30% dari total kasus. Saat ini belum ada biomarker yang efektif untuk memprediksi respon pasien terhadap terapi yang diberikan. Beberapa penelitian menggunakan potensi miRNA sebagai biomarker untuk melihat respon terapi. Salah satunya yaitu MiR-124-3p berperan sebagai tumor supresor yang mengalami penurunan ekspresi pada berbagi jenis kanker. Tujuan dari penelitian ini adalah untuk meneliti ekspresi miR-124-3p dari pasien kanker rektum yang menerima nCRT, dan menganalisis hubungannya dengan kelangsungan hidup pasien dan parameter klinis lainnya.
Metode: Penelitian ini melibatkan 15 orang pasien yang didiagnosis menderita kanker rektum lokal dan menjalani kemoradioterapi neoajuvan (radioterapi 45-50 Gy dengan fraksi 1,8-2 Gy selama 1-3 bulan, dan kemoterapi 5-fluororacil secara oral). Sampel penelitian berupa darah intravena sebanyak 5 ml diambil saat sebelum dan sesudah kemoradioterapi. Selanjutnya ekspresi miR-124-3p dianalisis menggunakan qRT-PCR dan dikalkulasi menggunakan metode Livak.
Hasil: Terdapat hubungan signifikan antara peningkatan ekspresi miR-124-3p dengan sintasan hidup pasien (P=0,003; OR =30, 95% CI = 1,41 – 638,15), serta adanya peningkatan ekspresi miR-124-3p yang signifikan (P<0,041, fold change sebelum=1,14 ± 1,25; sesudah=2,4 ± 1,84) setelah dilakukan kemoradioterapi.
Kesimpulan: Hasil ini mengindikasikan bahwa miR-124-3p berpotensi menjadi biomarker untuk memprediksi sintasan hidup pasien kanker rektum yang menerima kemoradioterapi. (Health Science Journal of Indonesia 2019;10(2):90-5)
Kata kunci: kanker rektum, kemoradioterapi, miR-124-3p, sintasan hidup
Abstract
Background: Colorectal cancer is the world’s third most prevalent cancer, which 30% of cases are rectal cancer. Today, the effective diagnostic marker to accurately predict clinical outcome patients response to therapy did not found yet. Several research studies have indicated that miRNA potential as a prognostic biomarker. MiR 124-3p plays as tumor suppressor that significantly down-regulated in some cancer and could radiosensitize human colorectal cancer cells. The aim of the study is to investigate the expression of miR-124-3p from rectal cancer patient who receive nCRT, and analyze its association with patient survival and others clinical parameters.
Methods: This research involved 15 patients with histologically confirmed locally advanced rectal cancer (LARC) and received neoadjuvant chemotherapy/nCRT (radiotherapy 45-50 Gy with 1,8-2 Gy fractions over 1 to 3 months and chemotherapy 5-fluorouracil was administered orally). Patient blood (5 ml) were collected from peripheral venous before and after neoadjuvant chemoradiotherapy. miR-124-3p expression was performed using qRT-PCR and calculate using Livak method.
Results: In this study, we found that increasing of miR-124 was significantly associate with high survival of rectal cancer patient (P = 0,003; OR =30, 95% CI = 1,41 – 638,15). Average of miR-124-3p expression increase significantly after nCRT (P<0,041, fold change before=1,14 ± 1,25; after=2,4 ± 1,84).
Conclusion: Our finding suggests that miR-124-3p expression in blood serum was potential as biomarkers to predict rectal cancer patient survival after neoajduvant chemoradiotherapy. (Health Science Journal of Indonesia 2019;10(2):90-5)
Keywords : rectal cancer, chemoradiotherapy, miR-124-3p, survival
References
World Health Organization [Internet]. Cancer. [cited 2019 March 10]. Available from: URL:https://www. who.int/news-room/factsheets/detail/ cancer.
Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33.
Conde-Muino R, Cuadros M, Zambudio N, Segura-Jimenez I, Cano C, Palma P. Predictive biomarkers to chemoradiation in locally advanced rectal cancer. BioMed Res Int. 2015. Article ID 921435 1-10.
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Bio. 2014;15(8):509 – 24.
Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015;15(6):321-33.
Wang Y, Chen L, Wu Z, Wang M, Jin F, Wang N, et al. miR-124-3p functions as a tumor suppressor in breast cancer by targeting CBL. BMC Cancer. 2016;16(826):1-9.
Luo L, Chi H, Ling J. Mir-124-3p suppresses glioma aggressiveness via targeting of Fra-2. Pathol Research Prac. 2018;214(11):1825-34.
Liu F, Hu H, Zhao J, Zhang Z, Ai X, Tang L, et al. miR-124-3p acts as a potential marker and suppresses tumor growth in gastric cancer. Biomed Rep. 2018;9(2):147-55.
Zhang Y, Zheng L, Huang J, Gao F,Lin X, He L, et al. Mir-124 radiosensitizes human colorectal cancer cells by targeting PRRX1. Plos One. 2014;9 (4):1-9.
Sun Y, Zhao X, Zhou Y, Hu Y. MiR-124, miR-137 and miR-340 regulate colorectal cancer growth via inhibition of the Warburg effect. Oncol Rep. 2012;28(4):1346 –52.
Kai K, Dittmar RL, Sen S. Secretory microRNA as biomarkers of cancer. Semin Cell Dev Biol. 2018;78:22-36.
Dagogo-Jack I, Shaw AT. Tumor heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2018;15(2):81-94.
Chiang C, Fu SY, Wang S, Yu C, Chen F, Lin C, et al. Irradiation promotes an M2 macrophage phenotype in tumor hypoxia. Front Oncol. 2012;2(89):1-12.
Torgovnick A, Scumacher B. DNA repair mechanism in cancer development and therapy. Front genet. 2015;6(157):1-15.
Yao WY, Kang KA, Piao MJ, Ryu YS, Fernando PMDJ, Oh MC, et al. Reduced autophagy in 5-fluororacil resistant colon cancer cells. Biomol Ther. 2017;25(3):315-20
Templin T. Radiation-induced micro-RNA expression changes in peripheral blood cells of radiotherapy patients. Int J Radiat Oncol. Biol Phys 2011;80(2):549–57.
Ondracek J. Global microRNA expression profiling identifies unique microRNA pattern of radioresistant glioblastoma cells. Anticancer Res. 2017;37(3):1099–104.
Jinushi T, Shibayama Y, Kinoshita I, Oizumi S, Jinushi M, Aota T, et al. Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4. Cancer Med. 2014;3(6):1544–52.
Hao C, Xu X, Ma J, Dai B, Liu L, Ma Y. Micro-RNA regulates the radiosensitivity of non-small cell lung cancer cells by targeting TXNRD1. Oncol Lett. 2017;13(4):2071-8.
Zhang YH, Wang QQ, Li H, Ye T, Gao F, Liu YC. miR-124 radiosensitize human esophageal cancer cell TE-1 by targeting CDK4. Genet Mol Res. 2016;15(2):1-10.
Wang MJ, Li Y, Wang R, Wang C, Yu YY, Yang L, et al. Down regulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer. Int J Colorectal Dis. 2013;(28)2:183-9.
Sun Y, Zhao X, Zhou Y, Hu Y. miR-124, miR-137 and miR-340 regulate colorectal cancer growth via inhibition of the Warburg effect. Oncol Rep. 2012;28(4):1346-52.
Qiu Z, Guo W, Wang Q, Chen Z, Huang S, Zhao F, et al. MicroRNA-124 reduces pentose phosphate pathway and proliferation by targeting PRPS1 and RPIA mRNAs in human colorectal cancer cells. Gastroenterology. 2015;149(6):1587-98.
Chen Z, Liu S, Tian L, Wu M, Ai F, Tang W, et al. miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1. Oncotarget. 2015;6(35):38139–50.
Copyright (c) 2019 Yanie Wahyuningrum
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
