SIRT6和survivin在胃癌组织中的表达及其临床意义

doi:10.3760/cma.j.cn371439-20191230-00005

摘要/Abstract

摘要：

目的分析沉默信息调节因子6(SIRT6)及survivin表达与胃癌患者临床病理学特征之间的关系,探讨其在胃癌中的作用。方法选取2013年3月至2014年10月西安交通大学第一附属医院收治的110例胃癌患者的肿瘤组织及对应的40例癌旁组织和20例正常组织,采用免疫组织化学法检测SIRT6和survivin的表达。分析二者表达水平与胃癌患者临床病理特征和预后的相关性。结果 SIRT6在胃癌组织、癌旁组织和正常组织中的阳性表达率分别为41.8%(46/110)、77.5%(31/40)、85.0%(17/20),3组差异具有统计学意义(χ ²=23.200,P<0.001),SIRT6在胃癌组织中的阳性表达率低于癌旁组织和正常组织(χ ²=14.949,P<0.001;χ ²=12.634,P<0.001),SIRT6的表达与肿瘤分化程度有关(χ ²=19.654,P<0.001);survivin在胃癌组织、癌旁组织和正常组织中的阳性表达率分别为58.2%(64/110)、15.0%(6/40)、0(0/20),3组差异具有统计学意义(χ ²=38.449,P<0.001),survivin在胃癌组织中的阳性表达率高于癌旁组织和正常组织(χ ²=21.976,P<0.001;χ ²=22.920,P<0.001),survivin的表达与胃癌浸润深度有关(χ ²=20.853,P<0.001)。SIRT6和survivin在胃癌组织中的表达相关(C=0.211,P=0.024)。生存分析表明,SIRT6阴性表达患者3年生存率为53.1%,低于阳性表达患者的78.3%,差异具有统计学意义(χ ²=4.004,P=0.045);survivin阳性表达患者的3年生存率为53.1%,阴性表达患者为78.3%,差异无统计学意义(χ ²=3.717,P=0.054)。Cox多因素回归分析显示,淋巴结有转移(RR=6.618,95%CI为2.152~20.358,P=0.001)与SIRT6阴性表达(RR=0.228,95%CI为0.081~0.644,P=0.005)均为胃癌患者预后不良的危险因素。结论 SIRT6在胃癌组织中低表达并与胃癌预后相关,survivin在胃癌组织中高表达,二者的表达呈负相关,提示二者表达失调可能在胃癌发生、发展中起重要作用。

关键词: 胃肿瘤, 预后, SIRT6, survivin

Abstract:

Objective To discuss the relationships between the expressions of silence information regulator 6 (SIRT6) and survivin and clinicopathological features of gastric cancer, and to investigate their effects in gastric cancer. Methods The tumor tissues of 110 gastric cancer patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2013 to October 2014, as well as 40 adjacent tissues and 20 normal tissues, were selected to detect the expressions of SIRT6 and survivin by immunohistochemistry. The correlations between the expression levels of SIRT6 and survivin and the clinicopathological features and prognosis of gastric cancer patients were analyzed. Results The positive rates of SIRT6 were 41.8% (46/110), 77.5% (31/40) and 85.0% (17/20) in gastric cancer, adjacent tissues and normal gastric tissues, respectively, and the difference among the three groups was statistically significant (χ ²=23.200, P<0.001). The positive rate of SIRT6 in gastric cancer tissue was lower than that in adjacent and normal tissues (χ ²=14.949, P<0.001; χ ²=12.634, P<0.001). The expression of SIRT6 was correlated with tumor differentiation (χ ²=19.654, P<0.001). The positive rates of survivin were 58.2% (64/110), 15.0% (6/40) and 0 (0/20) in gastric cancer, adjacent tissues and normal gastric tissues, respectively, and the difference among the three groups was statistically significant (χ ²=38.449, P<0.001). The positive rate of survivin in gastric cancer tissue was higher than that in adjacent and normal tissues (χ ²=21.976, P<0.001; χ ²=22.920, P<0.001). The expression of survivin was correlated with the depth of infiltration (χ ²=20.853, P<0.001). The expression of SIRT6 was correlated with survivin in gastric cancer tissues (C=0.211, P=0.024). Survival analysis showed that 3-year survival rate was 53.1% in the SIRT6 negative patients, lower than 78.3% in the positive patients, and the difference was statistically significant (χ ²=4.004, P=0.045), while the 3-year survival rates of the survivin positive and negative patients were 53.1% and 78.3%, and the difference was not significant (χ ²=3.717, P=0.054). Cox multivariate regression analysis showed that lymph node metastasis (RR=6.618, 95%CI: 2.152-20.358, P=0.001) and SIRT6 negative expression (RR=0.228, 95%CI: 0.081-0.644, P=0.005) were the risk factors for poor prognosis of gastric cancer. Conclusion SIRT6 is poorly expressed in gastric cancer tissues and is related to the prognosis of gastric cancer, while survivin is highly expressed in gastric cancer tissues. The expression of SIRT6 and survivin is negatively correlated, suggesting that the expression imbalance of SIRT6 and survivin may play an important role in the occurrence and development of gastric cancer.

Key words: Stomach neoplasms, Prognosis, SIRT6, Survivin

王颖, 杨伟, 肖菊香. SIRT6和survivin在胃癌组织中的表达及其临床意义[J]. 国际肿瘤学杂志, 2020, 47(4): 217-222.

Wang Ying, Yang Wei, Xiao Juxiang. Expressions of SIRT6 and survivin in gastric cancer tissue and their clinical significances[J]. Journal of International Oncology, 2020, 47(4): 217-222.

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参考文献 20

[1]	Gertler AA, Cohen HY . SIRT6, a protein with many faces[J]. Biogerontology, 2013,14(6):629-639. DOI: 10.1007/s10522-013-9478-8. doi: 10.1007/s10522-013-9478-8
[2]	Vitiello M, Zullo A, Servillo L , et al. Multiple pathways of SIRT6 at the crossroads in the control of longevity, cancer, and cardiovascular diseases[J]. Ageing Res Rev, 2017,35:301-311. DOI: 10.1016/j.arr.2016.10.008. doi: 10.1016/j.arr.2016.10.008
[3]	Ryan BM, O'Donovan N, Duffy MJ. Survivin: a new target for anti-cancer therapy[J]. Cancer Treat Rev, 2009,35(7):553-562. DOI: 10.1016/j.ctrv.2009.05.003. doi: 10.1016/j.ctrv.2009.05.003
[4]	Fromowitz FB, Viola MV, Chao S , et al. ras p21 expression in the progression of breast cancer[J]. Hum Pathol, 1987,18(12):1268-1275. DOI: 10.1016/s0046-8177(87)80412-4. doi: 10.1016/S0046-8177(87)80412-4
[5]	Mahlknecht U, Ho AD, Voelter-Mahlknecht S . Chromosomal organization and fluorescence in situ hybridization of the human Sirtuin 6 gene[J]. Int J Oncol, 2006,28(2):447-456.
[6]	Van Meter M, Mao Z, Gorbunova V , et al. SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells[J]. Cell Cycle, 2011,10(18):3153-3158. DOI: 10.4161/cc.10.18.17435. doi: 10.4161/cc.10.18.17435
[7]	Sebastián C, Zwaans BM, Silberman DM , et al. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism[J]. Cell, 2012,151(6):1185-1199. DOI: 10.1016/j.cell.2012.10.047. doi: 10.1016/j.cell.2012.10.047
[8]	Lai CC, Lin PM, Lin SF , et al. Altered expression of SIRT gene family in head and neck squamous cell carcinoma[J]. Tumour Biol, 2013,34(3):1847-1854. DOI: 10.1007/s13277-013-0726-y. doi: 10.1007/s13277-013-0726-y
[9]	Khongkow M, Olmos Y, Gong C , et al. SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer[J]. Carcinogenesis, 2013,34(7):1476-1486. DOI: 10.1093/carcin/bgt098. doi: 10.1093/carcin/bgt098
[10]	Min L, Ji Y, Bakiri L , et al. Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin[J]. Nat Cell Biol, 2012,14(11):1203-1211. DOI: 10.1038/ncb2590. doi: 10.1038/ncb2590
[11]	冯华 . SIRT6在胃癌中的表达变化及其机制研究[D]. 济南: 山东大学, 2016.
[12]	余长寿, 丁瑜, 曾锻 , 等. 去乙酰化酶6在胃癌中的表达[J]. 山西医科大学学报, 2015, ( 3):216-218. DOI: 10.13753/j.issn.1007-6611.2015.03.006.
[13]	Mostoslavsky R, Chua KF, Lombard DB , et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6[J]. Cell, 2006,124(2):315-329. DOI: 10.1016/j.cell.2005.11.044. doi: 10.1016/j.cell.2005.11.044
[14]	Sah NK, Khan Z, Khan GJ , et al. Structural, functional and therapeutic biology of survivin[J]. Cancer Lett, 2006,244(2):164-171. DOI: 10.1016/j.canlet.2006.03.007. doi: 10.1016/j.canlet.2006.03.007
[15]	欧阳勇文, 崔西玉, 黄辉文 , 等. 凋亡抑制蛋白Survivin在胃癌中的表达及其与预后的相关性分析[J]. 深圳中西医结合杂志, 2017,27(19):13-15. DOI: 10.16458/j.cnki.1007-0893.2017.19.005
[16]	Ito T, Shiraki K, Sugimoto K , et al. Survivin promotes cell proliferation in human hepatocellular carcinoma[J]. Hepatology, 2000,31(5):1080-1085. DOI: 10.1053/he.2000.6496. doi: 10.1053/he.2000.6496
[17]	薛军, 武雪亮, 高晓斌 , 等. 结直肠腺癌组织survivin和Ki-67的表达及其与预后的关系[J]. 基础医学与临床, 2015,35(11):1526-1530.
[18]	庞慧, 郭天利, 李宏建 . 血清CA153、Survivin蛋白在乳腺癌诊断的应用价值[J]. 中国现代药物应用, 2016,10(9):25-26. DOI: 10.14164/j.cnki.cn11-5581/r.2016.09.014.
[19]	Okada E, Murai Y, Matsui K , et al. Survivin expression in tumor cell nuclei is predictive of a favorable prognosis in gastric cancer patients[J]. Cancer Lett, 2001,163(1):109-116. DOI: 10.1016/s0304-3835(00)00677-7. doi: 10.1016/S0304-3835(00)00677-7
[20]	Kania J, Konturek SJ, Marlicz K , et al. Expression of survivin and caspase-3 in gastric cancer[J]. Dig Dis Sci, 2003,48(2):266-271. DOI: 10.1023/a:1021915124064. doi: 10.1023/A:1021915124064