Expression of ZMYND8 Protein in Gastric Cancer and Its Clinicopathological Significance

Abstract

Abstract: Objective To detect the expression of ZMYND8 in gastric cancer tissuesand their adjacent tissues, clarify the relationship between the expression level of ZMYND8 and the clinicopathological parameters of gastric cancer patients, and analyze the relationship between the expression of ZMYND8 and the 5-year survival rate of gastric cancer patients. Methods The expression of ZMYND8 mRNA in 30 cases of gastric cancer fresh tissues and the adjacent tissues were detected by RT-qPCR. Immunohistochemical was used to detect the expression of ZMYND8 protein in 60 cases of tumor and paraffinic samples. The correlation between the ZMYND8 expression and the survival rate of patients was analyzed by K-M survival curve. Results The expression of ZMYND8 mRNA in gastric cancer was significantly lower than that in the adjacent tissues (P<0.01). The positive rate of ZYND8 protein expression in gastric cancer was 21.6%, which was significantly lower than that in the adjacent tissues (85.0%, P<0.05). ZMYND8 expression was closely related to the depth of tumor cell invasion, lymph node metastasis and TNM stage (P<0.05). The results of K-M survival analysis showed that the 5-year survival rate of patients with positive expression of ZMYND8 was significantly higher than that of patients with low expression (P<0.01). Conclusion The expression rate of ZMYND8 in gastric cancer is low and closely related to tumor invasion, lymph node metastasis, TNM stage and 5-year survival rate of patients, which suggest that detection of the expression of ZMYND8 is of great significance in predicting the prognosis of gastric cancer patients.

Key words: gastric cancer, Bromine binding protein, survival rate, ZMYND8

摘要： 目的检测溴区结合蛋白ZMYND8在胃癌组织及相应癌旁组织中的表达,明确ZMYND8的表达水平与胃癌患者临床病理学参数之间的关系,并分析ZMYND8表达水平与胃癌患者5年生存率之间的相关性,以期明确其在判断胃癌患者预后中的作用。方法采用实时荧光定量PCR法（RT-qPCR）检测ZMYND8基因 mRNA在30例胃癌及癌旁新鲜组织中的表达;采用免疫组织化学SABC法检测ZMYND8蛋白在60例肿瘤及癌旁石蜡标本中的表达;ZMYND8蛋白表达水平与胃癌患者生存率之间的相关性采用K-M生存曲线分析。结果胃癌组织中ZMYND8 mRNA表达显著低于相对应的癌旁组织（P<0.01）;ZMYND8蛋白在胃癌组织中表达的阳性率为21.6%,显著低于癌旁中的85.0%（P<0.05）。ZMYND8的表达与肿瘤细胞浸润深度、淋巴结转移及TNM分期密切相关（P<0.05）,而与患者年龄、性别、肿瘤分化程度、远处转移无显著相关性（P>0.05）。K-M生存分析结果表明,癌组织中ZMYND8表达阳性的患者5年生存率显著高于阴性表达组,差异具有统计学意义（P<0.01）。结论 ZMYND8在胃癌组织中表达率低,且与肿瘤浸润、淋巴结转移、TNM分期及患者5年生存率密切相关,提示检测该基因的表达对预测胃癌患者预后具有重要意义。

关键词: 胃癌, 溴区结合蛋白, 生存率, ZMYND8

CLC Number:

R735.2

LIU Chang-bing, YAO Feng, NIU Duo-shan, ZHANG Zuo-yang. Expression of ZMYND8 Protein in Gastric Cancer and Its Clinicopathological Significance[J]. Journal of Chengde Medical University, 2020, 37(4): 271-274.

刘长兵, 姚丰, 牛多山, 张佐阳. 胃癌组织中ZMYND8蛋白的表达及临床病理学意义[J]. 承德医学院学报, 2020, 37(4): 271-274.

References

[1] Zhang AL, Chen L, Ma L, et al.Role of H3K18ac-regulated nucleotide excision repair-related genes in arsenic-induced DNA damage and repair of HaCaTcells[J]. Hum Exp Toxicol, 2020, 39(9):1168-1177.
[2] Choi CM, Yang SC, Jo HJ, et al.Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients[J]. Ann Oncol, 2012, 23(8): 2088-2093.
[3] Savitsky P, Krojer T, Fujisawa T, et al.Multivalent Histone and DNA Engagement by a PHD/BRD/PWWP Triple Reader Cassette Recruits ZMYND8 to K14ac-Rich Chromatin[J]. Cell Rep, 2016, 17(10): 2724-2737.
[4] Gong F, Clouaire T, Aguirrebengoa M, et al.Histone demethylase KDM5A regulates the ZMYND8-NuRD chromatin remodeler to promote DNA repair[J]. J Cell Biol, 2017, 216(7): 1959-1974.
[5] Yao N, Li J, Liu H, et al.The Structure of the ZMYND8/Drebrin Complex Suggests a Cytoplasmic Sequestering Mechanism of ZMYND8 by Drebrin[J]. Structure, 2017, 25(11): 1657-1666.
[6] Chen Y, Zhang B, Bao L, et al.ZMYND8 acetylation mediates HIF-dependent breast cancer progression and metastasis[J]. J Clin Invest, 2018, 128(5): 1937-1955.
[7] Li N, Li Y, Lv J, et al.ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes[J]. Mol Cell, 2016, 63(3): 470-484.
[8] Zhang ZY, Lu YX, Zhang ZY, et al.Loss of TINCR expression promotes proliferation, metastasis through activating EpCAM cleavage in colorectal cancer[J]. Oncotarget, 2016, 7(16): 22639-22649.
[9] 杨静,石晓虹,程玉,等. c-IAP1、c-IAP2和Beclin-1在胃癌组织中的研究进展[J].承德医学院学报,2017,34(02):142-145.
[10] Butt J, Varga MG, Wang T, et al.Smoking, Helicobacter Pylori Serology, and Gastric Cancer Risk in Prospective Studies from China, Japan, and Korea[J]. Cancer Prev Res (Phila), 2019, 12(10): 667-674.
[11] 李键淇,齐洁敏. CD44v4、整合素α2β1与胃癌[J]. 承德医学院学报,2015,32(03):238-241.
[12] Gong F, Miller KM.Double duty: ZMYND8 in the DNA damage response and cancer[J]. Cell Cycle, 2018, 17(4): 414-420.
[13] Zeng W, Kong Q, Li C, et al.Xenopus RCOR2 (REST corepressor 2) interacts with ZMYND8, which is involved in neural differentiation[J]. BiochemBiophys Res Commun, 2010, 394(4): 1024-1029.
[14] Mukherjee S, Sen S, Adhikary S, et al.A novel role of tumor suppressor ZMYND8 in inducing differentiation of breast cancer cells through its dual-histone binding function[J]. J Biosci, 2020, 45: 2.
[15] Chen J, Liu J, Chen X, et al.Low expression of ZMYND8 correlates with aggressive features and poor prognosis in nasopharyngeal carcinoma[J]. Cancer Manag Res, 2019, 11: 7835-7843.