探索ZRF1在原发性肝癌组织中的表达及临床意义

玉兰 衣(海军军医大学，转化医学研究中心临床肿瘤研究所，中国)
莎莎 陈(海军军医大学，转化医学研究中心临床肿瘤研究所，中国)
榃伦 曾(海军军医大学，转化医学研究中心临床肿瘤研究所，中国)
喜俊 梁(海军军医大学，转化医学研究中心临床肿瘤研究所，中国)

摘要

目的：研究ZRF1在原发性肝癌患者肿瘤组织中的表达情况，分析其与肝癌患者临床病理特征及预后的相关性。方法：收集243例经术后病理明确诊断为原发性肝癌患者的肿瘤组织样本，通过免疫组织化学法检测原发性肝癌肿瘤组织及相应癌旁组织中ZRF1的表达情况，采用Kaplan Meier生存分析法分析ZRF1的表达水平与原发性肝癌患者预后的相关性。结果：ZRF1在肝癌患者肿瘤组织中的阳性表达率显著低于对应的癌旁组织（P=0.015）；此外，ZRF1的表达与年龄、性别、门脉癌栓和肝硬化等临床病例特征均无统计学差异（P＞0.05），但与肿瘤大小呈现负相关趋势（P=0.056）；最后，在接受索拉非尼治疗的肝癌患者队列中，ZRF1低表达患者的预后显著优于ZRF1高表达的患者（P=0.020）。结论：ZRF1在原发性肝癌肿瘤组织中的表达水平低于其癌旁组织，且ZRF1的表达水平与原发性肝癌患者接受索拉非尼治疗的预后相关，有可能成为原发性肝癌患者接受索拉非尼治疗的疗效预测标志物。

关键词

ZRF1；原发性肝癌；索拉非尼；预后

参考

Llovet J M, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2016,14(2):16018.

Villanueva A. Hepatocellular Carcinoma[J]. N Engl J Med, 2019,11(15):1450-1462.

Torre L A, Bray F, Siegel R L, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015,65(2):87-108.

Zheng R, Qu C, Zhang S, et al. Liver cancer incidence and mortality in China: Temporal trends and projections to 2030[J]. Chin J Cancer Res, 2018,30(6):571-579.

Abdelgalil A A, Alkahtani H M, Al-Jenoobi F I. Sorafenib[J]. Profiles Drug Subst Excip Relat Methodol. 2019,44:239-266.

Aloia L, Demajo S, Di Croce L. ZRF1: a novel epigenetic regulator of stem cell identity and cancer[J]. Cell Cycle, 2015,14(4):510-515.

Liu H, Li J, Zhao H, et al. DNAJC2 is reversely regulated by miR6273p, promoting the proliferation of colorectal cancer[J]. Mol Med Rep, 2021,24(2):589.

Imamura T, Komatsu S, Ichikawa D, et al. Overexpression of ZRF1 is related to tumor malignant potential and a poor outcome of gastric carcinoma[J]. Carcinogenesis, 2018,39(2):263-271.

Demajo S, Uribesalgo I, Gutiérrez A, et al. ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia[J]. Oncogene, 2014,33(48):5501-5510.

Resto V A, Caballero O L, Buta M R, et al. A putative oncogenic role for MPP11 in head and neck squamous cell cancer[J]. Cancer Res, 2000,60(19):5529-5535.

Ribeiro J D, Morey L, Mas A, et al. ZRF1 controls oncogene-induced senescence through the INK4-ARF locus[J]. Oncogene, 2013,32(17):2161-2168.

Richly H, Rocha-Viegas L, Ribeiro J D, et al. Transcriptional activation of polycomb-repressed genes by ZRF1[J]. Nature, 2010,468(7327):1124-1128.

Kang M K. Polycomb group proteins: New targets of anti-cancer therapy[J]. Cell Cycle, 2010,9(14):2704.

Müller J, Verrijzer P. Biochemical mechanisms of gene regulation by polycomb group protein complexes[J]. Curr Opin Genet Dev, 2009,19(2):150-158.

Mills A A. Throwing the cancer switch: reciprocal roles of polycomb and trithorax proteins[J]. Nat Rev Cancer, 2010,10(10):669-682.

Richly H, Di Croce L. The flip side of the coin: role of ZRF1 and histone H2A ubiquitination in transcriptional activation[J]. Cell Cycle, 2011,10(5):745-750.

Li J, Xu Y, Long XD, et al. Cbx4 governs HIF-1α to potentiate angiogenesis of hepatocellular carcinoma by its SUMO E3 ligase activity[J]. Cancer Cell, 2014,25(1):118-131.

DOI: http://dx.doi.org/10.12345/yzlcyxzz.v4i9.8665