目的:探讨泛素特异性蛋白酶33(USP33)与胃癌患者临床病理特征及预后的关系。方法:收集60例胃癌患者的临床和随访资料,采用免疫组化MaxVision法检测胃癌组织和癌旁组织中USP33的表达水平,分析胃癌组织中USP33表达水平与患者临床病理特征及预后的关系。结果:与癌旁组织相比,USP33在胃癌患者癌组织中的表达水平降低(P＜0.05);胃癌组织中USP33表达水平与TNM分期、淋巴结转移、浸润深度呈负相关(P＜0.05);胃癌组织中USP33高表达的患者较USP33低表达的患者预后更好(P＜0.05);较低的肿瘤分化程度、较高的TNM分期、淋巴结转移阳性和低USP33表达水平是影响胃癌病人1年生存率的独立危险因素(P＜0.05)。结论:USP33在胃癌组织中表达下调,且其低表达与不良预后相关,表明USP33有可能作为一种分子生物标志物预测胃癌患者的预后,并成为未来胃癌治疗的新靶点。
Objective: To investigate the relationship between ubiquitin-specific protease 33 (USP33) and clinicopathological features and prognosis of patients with gastric cancer. Methods: The clinical and follow-up data of 60 patients with gastric cancer were collected. The expression level of USP33 in gastric cancer tissues and adjacent tissues was detected by immunohistochemical MaxVision method. The relationship between the expression level of USP33 in gastric cancer tissues and the clinicopathological features and prognosis of patients was analyzed. Results: Compared with adjacent tissues, the expression level of USP33 in gastric cancer tissues was decreased (P＜0.05). The expression level of USP33 in gastric cancer tissues was negatively correlated with TNM stage, lymph node metastasis and depth of invasion (P＜0.05). The prognosis of patients with high USP33 expression in gastric cancer tissues was better than that of patients with low USP33 expression (P＜0.05). Lower tumor differentiation, higher TNM stage, positive lymph node metastasis and low USP33 expression level were independent risk factors affecting the 1-year survival rate of gastric cancer patients (P＜0.05). Conclusion: USP33 is down-regulated in gastric cancer tissues, and its low expression is associated with poor prognosis, indicating that USP33 may be used as a molecular biomarker to predict the prognosis of gastric cancer patients and become a new target for future treatment of gastric cancer.
[1] 左婷婷,郑荣寿,曾红梅,等.中国胃癌流行病学现状[J].中国肿瘤临床,2017,44(1):52-58.
[2] 周荣健,张恒,束平,等.Ⅲ期胃癌根治术后预后因素分析及淋巴结转移率对预后的预测价值(附995例报告)[J].中华消化外科杂志,2019,18(3):250-258.
[3] Wilkinson KD. Regulation of ubiquitin-dependent processes by deubiquitinating enzymes[J]. FASEB J, 1997,11(14): 1245-1256.
[4] 申香玉,史磊,申远.泛素特异性蛋白酶在肿瘤发生发展中的作用[J].生命的化学,2021,41(4):693-706.
[5] 潘新宇,赵玉,于建渤.去泛素化酶USP33的研究进展[J].临床与实验病理学杂志,2019,35(10):1207-1209.
[6] Bold R. “development of the proteasome inhibitor velcade (bortezomib)” by Julian Adams, Ph.D., and Michael kauffman, M.D., Ph.D[J]. Cancer Invest, 2004,22(2): 328-329.
[7] Steele JM. Carfilzomib: a new proteasome inhibitor for relapsed or refractory multiple myeloma[J]. J Oncol Pharm Pract, 2013,19(4): 348-354.
[8] Chen Y, Pang XM, Ji LJ, et al. Reduced expression of deubiquitinase USP33 is associated with tumor progression and poor prognosis of gastric adenocarcinoma[J]. Med Sci Monit, 2018,24:3496-3505.
[9] 国家卫生健康委员会. 胃癌诊疗规范(2018年版)[J].中华消化病与影像杂志(电子版),2019,9(3):118-144.
[10] 陕飞,李子禹,张连海,等. 国际抗癌联盟及美国肿瘤联合会胃癌TNM分期系统(第8版)简介及解读[J].中国实用外科杂志,2017,37(1):15-17.
[11] Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification[J]. Acta Pathol Microbiol Scand, 1965,64:31-49.
[12] Urano N, Fujiwara Y, Doki Y, et al. Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma[J]. Gastric Cancer, 2006,9(1): 44-49.
[13] Tamura G, Kihana T, Nomura K, et al. Detection of frequent p53 gene mutations in primary gastric cancer by cell sorting and polymerase chain reaction single-strand conformation polymorphism analysis[J]. Cancer Res, 1991,51(11): 3056-3058.
[14] Soucy TA, Smith PG, Milhollen MA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer[J]. Nature, 2009,458(7239): 732-736.
[15] Hershko A, Ciechanover A. The ubiquitin system[J]. Annu Rev Biochem, 1998,67:425-479.
[16] Hoeller D, Dikic I. Targeting the ubiquitin system in cancer therapy[J]. Nature, 2009,458(7237): 438-444.
[17] Tobinai K. Proteasome inhibitor, bortezomib, for myeloma and lymphoma[J]. Int J ClinOncol, 2007,12(5): 318-326.
