罗含欢;师杰;边巴扎西;杨旭;尼玛卓玛;王倩;李梅;王寒;廖瑞倩;次仁曲珍;
LUO Hanhuan;SHI Jie;BIANBA Zhaxi;YANG Xu;NIMA Zhuoma;WANG Qian;LI Mei;WANG Han;LIAO Ruiqian;CIREN Quzhen;Department of Pathology,Tibet Autonomous Region People's Hospital;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;Department of General Surgery,Tibet Autonomous Region People's Hospital;Department of Liver Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical Col

• 1:西藏自治区人民医院病理科
• 2:中国医学科学院北京协和医院病理科
• 3:西藏自治区人民医院普外科
• 4:中国医学科学院北京协和医院肝脏外科

摘要(Abstract)：

目的 探究H3K27me3在西藏地区藏族人群胃癌组织中的表达水平及其与临床、病理特征的相关性。方法 回顾性收集2019年8月至2021年8月西藏自治区人民医院藏族胃癌患者及同期藏族非胃癌患者的临床与病理资料。采用免疫组化法检测胃癌患者手术切除的肿瘤组织、癌旁正常胃黏膜组织及非胃癌患者正常胃黏膜组织中H3K27me3表达情况，并比较不同临床与病理特征胃癌患者之间H3K27me3表达差异。结果 共入选符合纳入和排除标准的藏族胃癌患者54例，藏族非胃癌患者55例。H3K27me3定位于细胞核，阳性表达时细胞核呈棕黄色颗粒状着色。胃癌组织中H3K27me3高表达率显著高于癌旁正常胃黏膜组织[64.8%(35/54)比29.6%(16/54),P<0.001]和非胃癌患者正常胃黏膜组织[64.8%(35/54)比34.5%(19/55),P=0.002],癌旁正常胃黏膜组织中H3K27me3高表达率与非胃癌患者正常胃黏膜组织无显著差异(P=0.683)。H3K27me3表达水平在不同年龄、性别及Lauren分型、分化程度、浸润深度、肿瘤最大径、TNM分期等胃癌患者之间均无显著差异(P均>0.05)。结论西藏地区藏族人群胃癌组织中H3K27me3表达水平显著增高，暂未发现H3K27me3表达水平与藏族胃癌患者临床及病理特征具有相关性。
Objective To investigate the expression and its significance of H3 K27 me3 in Tibetan patients with gastric cancer.Methods Clinical and pathological data were retrospectively collected from Tibetan patients with gastric cancer in the Tibet Autonomous Region People's Hospital from August 2019 toAugust 2021 and Tibetan non-gastric cancer patients during the same period. The expression of H3 K27 me3 in gastric cancer tissues, corresponding adjacent normal gastric mucosa and normal gastric mucosa of Tibetan patients with non-gastric cancer tissues was detected by immunohistochemical method, and the differences of H3 K27 me3 expression between gastric cancer patients with different clinical and pathological characteristics was compared. Results A total of 54 Tibetan gastric cancer patients and 55 Tibetan non-gastric cancer patients who met the inclusion and exclusion criteria were enrolled. H3 K27 me3 was localized in the nucleus, and the nucleus showed brownish-yellow granular staining when positively expressed. The high expression rate of H3 K27 me3 in gastric cancer tissues was significantly higher than that in adjacent normal gastric mucosa tissue[64.8%(35/54) vs. 29.6%(16/54), P<0.001]and normal gastric mucosal tissue of Tibetan patients with non-gastric cancer[64.8%(35/54) vs. 34.5%(19/55), P=0.002], and the high expression rate of H3 K27 me3 in the adjacent normal gastric mucosa tissue was not significantly different from that in normal gastric mucosal tissue of Tibetan patients with non-gastric cancer(P=0.683). H3 K27 me3 expression in gastric cancer tissues was not related to gender, age, degree of differentiation, depth of invasion, maximum tumor size, Lauren's classification, lymph node metastasis, vascular and nerve invasion and TNM stage. Conclusions H3 K27 me3 is highly expressed in gastric cancer tissues of Tibetan people in Tibet. There is no significant difference in H3 K27 me3 positive expression cells in adjacent tissues and normal gastric mucosa. The significance of H3 K27 me3 in Tibetan patients with gastric cancer is uncertain and requires further investigations.

关键词(KeyWords)： 西藏自治区;藏族;胃癌;H3K27me3;病理特征
Tibet autonomous region;Tibetan;gastric cancer;H3K27me3;pathological features

Abstract:

Keywords:

基金项目(Foundation): 西藏自治区自然科学基金组团式援藏医学项目(XZ2017ZR-ZY33)~~

作者(Authors): 罗含欢;师杰;边巴扎西;杨旭;尼玛卓玛;王倩;李梅;王寒;廖瑞倩;次仁曲珍;
LUO Hanhuan;SHI Jie;BIANBA Zhaxi;YANG Xu;NIMA Zhuoma;WANG Qian;LI Mei;WANG Han;LIAO Ruiqian;CIREN Quzhen;Department of Pathology,Tibet Autonomous Region People's Hospital;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College;Department of General Surgery,Tibet Autonomous Region People's Hospital;Department of Liver Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical Col

参考文献(References)：

• [1] Sung H,Ferlay J,Siegel RL,et al.Global Cancer Statistics 2020:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J].CA Cancer J Clin,2021,71:209- 249.
• [2] 旦增，李康，王中华，等.拉萨地区社区人群的胃癌流行病学特征[J].世界华人消化杂志，2013,21:2104- 2108.Dan Z,Li K,Wang ZH,et al.Epidemiological features of gastric cancer in a community population in Lhasa[J].Shijie Huaren Xiaohua Zazhi,2013,21:2104- 2108.
• [3] Kurdistani SK.Histone modifications in cancer biology and prognosis[J].Prog Drug Res,2011,67:91- 106.
• [4] Bates SE.Epigenetic Therapies for Cancer[J].N Engl J Med,2020,383:650- 663.
• [5] Xiao W,Zhou Q,Wen X,et al.Small Molecule Inhibitors Overcome Epigenetic Reprogramming for Cancer Therapy[J].Front Pharmacol,202,12:702360.
• [6] Nam NH,Huong TL,Dung do TM,et al.Novel isatin-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents[J].Eur J Med Chem,2013,70:477- 486.
• [7] Luu T,Frankel P,Beumer J H,et al.Phase I trial of belinostat in combination with 13-cis-retinoic acid in advanced solid tumor malignancies:a California Cancer Consortium NCI/CTEP sponsored trial[J].Cancer Chemother Pharmacol,2019,84:1201- 1208.
• [8] Imai Y,Hirano M,Kobayashi M,et al.HDAC Inhibitors Exert Anti-Myeloma Effects through Multiple Modes of Action[J].Cancers (Basel),2019,11:475.
• [9] Zang H,Qian G,Zong D,et al.Overcoming acquired resistance of epidermal growth factor receptor-mutant non-small cell lung cancer cells to osimertinib by combining osimertinib with the histone deacetylase inhibitor panobinostat(LBH589)[J].Cancer,2020,126:2024- 2033.
• [10] Tanimoto A,Takeuchi S,Arai S,et al.Histone deacety-lase 3 inhibition overcomes BIM deletion polymorphism-mediated osimertinib resistance in EGFR-Mutant lung cancer[J].Clin Cancer Res,2017,23:3139- 3149.
• [11] Zhang L,Zhong K,Dai Y,et al.Genome-wide analysis of histone H3 lysine 27 trimethylation by ChIP-chip in gastric cancer patients[J].J Gastroenterol,2009,44:305- 312.
• [12] Huang H,Xie L,Feng X,et al.An integrated analysis of DNA promoter methylation,microRNA regulation,and gene expression in gastric adenocarcinoma[J].Ann Transl Med,2021,9:1414.
• [13] Li Y,Guo D,Sun R,et al.Methylation Patterns of Lys9 and Lys27 on Histone H3 Correlate with Patient Outcome in Gastric Cancer[J].Dig Dis Sci,2019,64:439- 446.
• [14] WHO Classification Tumours Editorial Board.WHO classification of tumours of digestive system[M].Lyon:LARC Press,2019.
• [15] Samal S,Patnaik A,Sahu F,et al.Altered expression of epigenetic modifiers EZH2,H3K27me3,and DNA methyltransferases in meningiomas-prognostic biomarkers for routine practice[J].Folia Neuropathol,2020,58:133- 142.
• [16] 高福利，吕瑛，曹俊，等.H3K27me3在胃癌中的表达及其临床意义[J].世界华人消化杂志，2011,19:3597- 3602.GaoFL,LYU Y,Cao J,et al.Significance of H3K27me3 expression in gastric cancer[J].Shijie Huaren Xiaohua Zazhi,2011,19:3597- 3602.
• [17] He LJ,Cai MY,Xu GL,et al.Prognostic significance of overexpression of EZH2 and H3K27me3 proteins in gastric cancer[J].Asian Pac J Cancer Prev,2012,13:3173- 3178.
• [18] 高恩惠，刘丹，陈洁，等.H3K27me3在肿瘤中的表达及其应用[J].中国新药与临床杂志，2021,40:406- 410.Gao EH,Liu D,Chen J,et al.Expression of H3K27me3 in tumors and its application[J].Zhongguo Xinyao Yu Linchuang Zazhi,2021,40:406- 410.
• [19] Hong F,Zhao M,Zhang L,et al.Inhibition of Ezh2 in vitro and the decline of Ezh2 in developing midbrain promote dopami-nergicneurons differentiation through modifying H3K27me3[J].Stem Cells Dev,2019,28:649- 658.
• [20] 张宁，曾智，阎丽萍，等.幽门螺杆菌感染与胃癌中 PRC2 和 H3K27me3 的表达关系[J].临床研究与应用杂志，2018,45:667- 672.Zhang N,Zeng Z,Yan LP,et al.Relationship between Helicobacter pylori infection and the expression of PRC2 and H3K27me3 in gastric cancer[J].Linchuang Yanjiu Yu Yingyong Zazhi,2018,45:667- 672.