Abstract:Objective: To investigate the association between the expression levels of microRNA-1470 (miR-1470), POZ domain and AT-binding motif zinc finger protein 1 (PATZ1) in hepatocellular carcinoma (HCC) tissues and patient prognosis within 5 years. Methods: A total of 135 patients with HCC who underwent radical resection at Handan Central Hospital from September 2015 to August 2018 were enrolled in this study. HCC tissues and corresponding adjacent normal tissues (normal liver tissues more than 2 cm away from the tumor margin) were collected during surgery. Immunohistochemistry was used to detect PATZ1 protein expression; real-time fluorescence quantitative PCR was used to detect miR-1470 and PATZ1 mRNA expression. Patients were followed up for 5 years, and 5-year overall survival rates were calculated. The expression of miR-1470 and PATZ1 mRNA and protein in HCC tissues and adjacent normal tissues was compared; the relationship between miR-1470 and PATZ1 mRNA expression and clinicopathological parameters, their correlation, and their association with prognosis were analyzed; and the risk factors affecting prognosis were identified. Dual luciferase reporter gene assay was used to verify the target relationship between miR-1470 and PATZ1. Results: The positive expression rate of PATZ1 protein in HCC tissues was significantly lower than that in adjacent normal tissues (P<0.05). Compared with adjacent normal tissues, the expression level of miR-1470 was significantly upregulated and the expression level of PATZ1 mRNA was significantly downregulated in HCC tissues (P<0.05). Patients with low miR-1470 and high PATZ1 mRNA expression in HCC tissues had significant differences in serum alpha-fetoprotein (AFP) level, China Liver Cancer Staging System (CNLC) stage, and the presence or absence of vascular tumor thrombus (P<0.05). The expression of miR-1470 and PATZ1 mRNA was negatively correlated in HCC tissues (P<0.05). The 5-year overall survival rates of patients with low miR-1470 expression and high PATZ1 mRNA expression were significantly higher than those of patients with high miR-1470 expression and low PATZ1 mRNA expression (P<0.05). CNLC stage III, vascular tumor thrombus, high miR-1470 expression, and low PATZ1 mRNA expression were independent risk factors for poor prognosis in HCC patients (P<0.05). miR-1470 could negatively regulate PATZ1 expression. Conclusion: miR-1470 is upregulated and PATZ1 is downregulated in HCC tissues, and the two are negatively correlated. Both can be used as biomarkers to evaluate the prognosis of HCC patients, and miR-1470 can negatively regulate PATZ1 expression.
[1] Fadhil RS,Wei MQ,Nikolarakos D,et al.Salivary microRNA miR-let-7a-5p and miR-3928 could be used as potential diagnostic bio-markers for head and neck squamous cell carcinoma[J].PLoS One,2020,15(3):221779. [2] 陆轶杰,蒋新卫,吴建武.miR-1470对人肝癌细胞增殖和凋亡的影响[J].肝胆胰外科杂志,2020,32(2):97-101. [3] Luca S,Franco R,Napolitano A,et al.PATZ1 in non-small cell lung cancer:a new biomarker that negatively correlates with PD-L1 expression and suppresses the malignant phenotype[J].Cancers (Basel),2023,15(7):2190-2211. [4] 中华人民共和国国家卫生健康委员会医政医管局.原发性肝癌诊疗规范(2019年版)[J].中华消化外科杂志,2020,19(1):1-20. [5] Elmeliegy M,Yang DZ,Salama E,et al.Discordance between child-pugh and national cancer institute classifications for hepatic dysfunction:implications on dosing recommendations for oncology compounds[J].Clin Pharmacol,2021,61(1):105-115. [6] 董文亮,刘洪涛,初侃,等.泛素偶联酶E2C在原发性肝癌中的表达及与临床病理参数和预后的关系[J].疑难病杂志,2020,19(10):994-998. [7] Tian K,Ying Y,Huang J,et al.The expression,immune infiltration,prognosis,and experimental validation of OSBPL family genes in liver cancer[J].BMC Cancer,2023,23(1):244-254. [8] Farberov L,Ionescu A,Zoabi Y,et al.Multiple copies of microRNA binding sites in long 3'UTR variants regulate axonal translation[J].Cells,2023,12(2):233-257. [9] Lai Y,Liu J,Hu X,et al.Modifications of the human liver cancer cells through microRNA-145-mediated targeting of CDCA3[J].Cell,2023,25(8):546-553. [10] Lu Y,Yang L,Qin A,et al.miR-1470 regulates cell proliferation and apoptosis by targeting ALX4 in hepatocellular carcinoma[J].Biochem Biophys Res Commun,2020,522(3):716-723. [11] Akazawa Y,Mizuno S,Fujinami N,et al.Usefulness of serum microRNA as a predictive marker of recurrence and prognosis in biliary tract cancer after radical surgery[J].Sci Rep,2019,9(1):5925-5927. [12] Tauziede-Espariat A,Chotard G,Le Loarer F,et al.A novel LARGE1-AFF2 fusion expanding the molecular alterations associated with the methylation class of neuroepithelial tumors with PATZ1 fusions[J].Acta Neuropathol Commun,2022,10(1):15-19. [13] Vitiello M,Palma G,Monaco M,et al.Dual oncogenic/anti-oncogenic role of PATZ1 in FRTL5 rat thyroid cells transformed by the Ha-rasV12 oncogene[J].Genes (Basel),2019,10(2):127-130. [14] 李秀娟,郑雪绒,赵欣媛,等.PATZ1通过激活p53依赖性途径抑制宫颈癌细胞增殖和迁移的机制研究[J].山西医科大学学报,2020,51(6):499-505.