目的：探究肝切除术治疗早期肝细胞癌对患者血清中miR-375、miR-122、中期因子（MDK）、甲胎蛋白（AFP）和Ku86抗体水平的影响。方法：选取2015年6月至2018年6月本院收治的90例早期肝细胞癌患者为研究对象，采用实时荧光定量PCR反应（RT-qPCR）试验在RNA水平上检测miR-375和miR-122的表达，用酶联免疫吸附试验（ELISA）在蛋白水平上检测MDK、AFP和Ku86抗体的表达。结果：与治疗前相比，肝切除术后患者血清中的miR-375和miR-122的相对表达量明显上升，MDK、AFP和Ku86抗体的蛋白表达水平明显下降，治疗前后比较差异均有统计学意义（P<0.05）。结论：肝切除术治疗早期肝细胞癌后患者血清miR-375、miR-122表达水平上升，而MDK、AFP和Ku86抗体的蛋白表达水平下降，这些水平变化可作为临床评价疗效的辅助指标。

[1] BERRETTA M,STANZIONE B,DI FRANCIA R,et al.The expression of PD-L1 APE1 and P53 in hepatocellular carcinoma and its relationship to clinical pathology[J].Eur Rev Med Pharmacol Sci,2015,19(22):4207-4209.
[2] JEMAL A,BRAY F,CENTER M M,et al.Global cancer statistics[J].CA Cancer J Clin,2011,61(2):69-90.
[3] THAKRAL S,GHOSHAL K.miR-122 is a unique molecule with great potential in diagnosis,prognosis of liver disease,and therapy both as miRNA mimic and antimir[J].Curr Gene Ther,2015,15(2):142-150.
[4] COULOUARN C,FACTOR V M,ANDERSEN J B,et al.Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties[J].Oncogene,2009,28(40):3526-3536.
[5] HE X X,CHANG Y,MENG F Y,et al.MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo[J].Oncogene,2012,31(28):3357-3369.
[6] ZHU W W,GUO J J,GUO L,et al.Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma[J].Clin Cancer Res,2013,19(14):3944-3954.
[7] 储磊,张霞军,王国忠,等.抗Ku86抗体在肝细胞癌早期诊断中的价值[J].中华肿瘤杂志,2014,36(2):123-127.
[8] XIE D,YUAN P,WANG D,et al.Expression and prognostic significance of miR-375 and miR-221 in liver cancer[J].Oncol Lett,2017,14(2):2305-2309.
[9] WALLACE M C,PREEN D,JEFFREY G P,et al.The evolving epidemiology of hepatocellular carcinoma:a global perspective[J].Expert Rev Gastroenterol Hepatol,2015,9(6):765-779.
[10] DE SANTIBANES E,MC CORMACK L,PEKOLJ J,et al.[Multimodal treatment of hepatocellular carcinoma] [J].Acta Gastroenterol Latinoam,2001,31(5):367-375.
[11] 胡秀秀,潘玉琴,王书奎.MicroRNA-485-5p抑制人结直肠癌细胞增殖和侵袭作用的研究[J].东南大学学报(医学版),2018,37(5):72-77.
[12] 常芬,肖贵华,李琪.上调microRNA-214表达对肺癌细胞凋亡及耐药性的影响[J].东南大学学报(医学版),2017,36(5):811-815.
[13] 高细强,龙石银,乔新惠.miRNA与肝细胞癌的研究进展[J].医学综述,2011,17(24):3711-3714.
[14] GAILHOUSTE L,GOMEZ-SANTOS L,OCHIYA T.Potential applications of miRNAs as diagnostic and prognostic markers in liver cancer[J].Front Biosci (Landmark Ed),2013,18(1):199-223.
[15] CHANG Y,YAN W,HE X,et al.miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions[J].Gastroenterology,2012,143(1):177-187.
[16] HSU S H,WANG B,KOTA J,et al.Essential metabolic,anti-inflammatory,and anti-tumorigenic functions of miR-122 in liver[J].J Clin Invest,2012,122(8):2871-2883.
[17] 王跃华,江涛,张斌,等.肝细胞癌中miR-122的表达及其与血清AFP水平的关系[J].临床肿瘤学杂志,2012,17(8):704-707.
[18] BANDIERA S,PFEFFER S,BAUMERT T F,et al.miR-122-a key factor and therapeutic target in liver disease[J].J Hepatol,2015,62(2):448-457.
[19] DING C,HE J,ZHAO J,et al.β-catenin regulates IRF3-mediated innate immune signalling in colorectal cancer[J].Cell Prolif,2018,51(5):e12464.
[20] YANG X,XIONG Q,WU Y,et al.Quantitative proteomics reveals the regulatory networks of circular RNA CDR1as in hepatocellular carcinoma cells[J].J Proteome Res,2017,16(10):3891-3902.
[21] 余婷婷,李冬玲,普冬,等.AFP、PIVKA-Ⅱ和CEA检测在肝细胞癌临床诊断中的应用[J].检验医学与临床,2017,14(Z1):92-94.
[22] VONGSUVANH R,VAN DER POORTEN D,ISELI T,et al.Midkine increases diagnostic yield in AFP negative and NASH-related hepatocellular carcinoma[J].PLoS One,2016,11(5):e0155800.
[23] JIA H L,YE Q H,QIN L X,et al.Gene expression profiling reveals potential biomarkers of human hepatocellular carcinoma[J].Clin Cancer Res,2007,13(4):1133-1139.
[24] MURAMATSU T.Midkine and pleiotrophin:two related proteins involved in development,survival,inflammation and tumorigenesis[J].J Biochem,2002,132(3):359-371.
[25] 朱文伟,张巨波,郭磊,等.Midkine(MDK)在肝细胞癌(HCC)中的表达及其临床意义[J].复旦学报(医学版),2013,40(1):55-59.
[26] SOMEYA M,SAKATA K I,MATSUMOTO Y,et al.The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer[J].Br J Cancer,2011,104(11):1724-1729.
[27] TONG W M,CORTES U,HANDE M P,et al.Synergistic role of Ku80 and poly(ADP-ribose) polymerase in suppressing chromosomal aberrations and liver cancer formation[J].Cancer Res,2002,62(23):6990-6996.
[28] NOMURA F,SOGAWA K,NODA K,et al.Serum Ku86抗体is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma[J].Biochem Biophys Res Commun,2012,421(4):837-843.