原发性肝细胞癌组织PD-L1、MDR1表达变化及其临床意义
摘要
目的探讨原发性肝细胞癌(以下称肝癌)组织细胞程序性死亡配体1(PD-L1)、多药耐药基因1(MDR1)表达变化及其临床意义。方法选择原发性肝癌组织及其配对的癌旁正常组织各90例份,采用免疫组化法检测PD-L1、MDR1表达,并分析原发性肝癌组织PD-L1表达与MDR1表达的关系。取传3代、对数生长期肝癌细胞Huh7,随机分为观察组和对照组,分别转染pEGFP-PD-L1和pEGFP-N1质粒。转染48 h,采用real-time PCR法检测PD-L1、MDR1 mRNA表达,采用Western blotting法检测PD-L1、MDR1蛋白表达。结果原发性肝癌组织PD-L1、MDR1阳性表达率均明显高于癌旁正常组织(P均<0.01)。Spearman秩相关分析显示,原发性肝癌组织PD-L1表达与MDR1表达呈正相关关系(r=0.594,P<0.01)。转染48 h,观察组PD-L1、MDR1 mRNA和蛋白表达均明显高于对照组(P均<0.01)。结论原发性肝癌组织PD-L1表达明显升高,其表达变化可能与肝癌化疗耐药有关。
引文
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[15] 周婷,严玉荣,赵晨辰,等.PD-L1蛋白过表达对HeLa细胞迁移能力的影响[J].生物技术,2017,27(6):557-562.
[2] Chang H, Jung W, Kim A, et al. Expression and prognostic significance of programmed death protein 1 and programmed death ligand-1, and cytotoxic T lymphocyte-associated molecule-4 in hepatocellular carcinoma[J]. APMIS, 2017,125(8):690-698.
[3] Liu B, Song Y, Liu D. Recent development in clinical applications of PD-1 and PD-L1 antibodies for cancer immunotherapy[J]. J Hematol Oncol, 2017,10(1):174.
[4] Dai X, Pi G, Yang SL, et al. Association of PD-L1 and HIF-1α coexpression with poor prognosis in hepatocellular carcinoma[J]. Transl Oncol, 2018,11(2):559-566.
[5] Li F, Ren Y, Wang Z. Programmed death 1 Ligand 1 expression in breast cancer and its association with patients′ clinical parameters[J]. J Cancer Res Ther, 2018,14(1):150-154.
[6] Zhang L, Qiu M, Jin Y, et al. Programmed cell death ligand 1 (PD-L1) expression on gastric cancer and its relationship with clinicopathologic factors[J]. Int J Clin Exp Patho, 2015,8(9):11084-11091.
[7] Li W, Li J, Wang R, et al. MDR1 will play a key role in pharmacokinetic changes under hypoxia at high altitude and its potential regulatory networks[J]. Drug Metab Rev, 2015,47(2):191-198.
[8] Mealey KL, Fidel J. P-glycoprotein mediated drug interactions in animals and humans with cancer[J]. J Vet Intern Med, 2015,29(1):1-6.
[9] Liu S, Chen S, Yuan W, et al. PD-1/PD-L1 interaction up-regulates MDR1/P-gp expression in breast cancer cells via PI3K/AKT and MAPK/ERK pathways[J]. Oncotarget, 2017,8(59):99901-99912.
[10] Vander Borght S, Komuta M, Libbrecht L, et al. Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin[J]. Liver Int, 2010,28(10):1370-1380.
[11] Calderaro J, Rousseau B, Amaddeo G, et al. Programmed death ligand 1 expression in hepatocellular carcinoma: relationship with clinical and pathological features[J]. Hepatology, 2016,64(6):2038-2046.
[12] Gevensleben H, Dietrich D, Golletz C, et al. The immune checkpoint regulator PD-L1 is highly expressed in aggressive primary prostate cancer[J]. Clin Cancer Res, 2015,22(8):1969-1977.
[13] Gao Q, Wang XY, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma[J]. Clin Cancer Res, 2009,15(3):971-979.
[14] Han HK, Han CY, Cheon EP, et al. Role of hypoxia-inducible factor-alpha in hepatitis-B-virus X protein-mediated MDR1 activation[J]. Biochem Biophys Res Commun, 2007,357(2):567-573.
[15] 周婷,严玉荣,赵晨辰,等.PD-L1蛋白过表达对HeLa细胞迁移能力的影响[J].生物技术,2017,27(6):557-562.