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摘要:
目的 评价菱形结构域蛋白(rhomboid domain-containing protein 1, RHBDD1)在胃癌中的表达及其与胃癌发生、发展的关系。 方法 回顾性收集2015年1月至2018年1月北京医院消化内科收治的胃癌、癌前病变以及慢性浅表性胃炎患者的临床资料, 对病变的组织病理学诊断结果进行重新判读。根据病理诊断类型将入组患者的胃黏膜组织分为慢性浅表性胃炎(chronic superficial gastritis, CSG)、低级别上皮内瘤变(low-grade gastric intraepithelial neoplasia, LGIN)、高级别上皮内瘤变(high-grade gastric intraepithelial neoplasia, HGIN)、早期胃癌(early gastric cancer, EGC)和进展期胃癌(advanced gastric cancer, AGC)5组, 记录各组免疫组化检测RHBDD1在胃黏膜组织中的表达阳性率, 分析各组之间的差异。 结果 共76例152处病变入选本研究, 其中CSG 17处, LGIN 21处、HGIN 54处、EGC 44处、AGC 16处。CSG组织中RHBDD1的表达显著低于非CSG病变(LGIN、HGIN、EGC和AGC), 具有统计学差异(χ2=13.157, P=0.001)。病变胃黏膜RHBDD1表达的阳性率随病变严重程度逐渐升高[CSG(35.3%)→癌前病变(LGIN+HGIN)(74.7%)→EGC(75.0%)→AGC(87.5%)]。 结论 胃黏膜组织中RHBDD1的表达有可能为胃部疾病的良恶性鉴别提供有用线索。 Abstract:Objective This study aimed to investigate the expression of rhomboid domain-containing protein 1(RHBDD1)in the tissue of gastric cancer, and to evaluate its relationship with the occurrence and development of gastric cancer. Methods We retrospectively collected the clinical data of patients with gastric cancer, precancerous lesions, or chronic superficial gastritis(CSG)admitted in the Department of Gastroenterology, Beijing Hospital from January 2015 to January 2018. The histopathological diagnosis of the lesions was reinterpreted. According to the type of pathological diagnosis, the lesions were divided into groups of CSG, low-grade gastric intraepithelial neoplasia(LGIN), high-grade gastric intraepithelial neoplasia(HGIN), early gastric cancer(EGC), and advanced gastric cancer(AGC). The positive rate of the expression of RHBDD1 in the gastric tissue was analyzed. Results A total of 76 patients with 152 lesions were enrolled in this study, including CSG 17, LGIN 21, HGIN 54, EGC 44, and AGC 16. The expression of RHBDD1 in chronicgastritis was significantly lower than that in other gastric lesions, including LGIN, HGIN, EGC, and AGC(P=0.001). The general trend of positive RHBDD1 expression in gastric mucosal lesions increased gradually with the severity[CSG(35.3%)→precancerous lesions(LGIN+HGIN)(74.7%)→EGC(75.0%)→AGC(87.5%)]. Conclusion The expression of RHBDD1 in the gastric tissue may provide a useful clue for the differentiation between benign and malignant gastric diseases. 利益冲突 无 -
表 1 152处不同胃黏膜病变组织中RHBDD1表达水平[n(%)]
病变类型 RHBDD1阴性
(n=42)RHBDD1阳性
(n=110)χ2值 P值 CSG(n=17) 11(64.7) 6(35.3) 13.157 0.001* 非CSG(n=135) 31(23.0) 104(77.0) LGIN(n=21) 6(28.6) 15(71.4) HGIN(n=54) 12(22.2) 42(77.8) EGC(n=44) 11(25.0) 33(75.0) AGC(n=16) 2(12.5) 14(87.5) CSG:慢性浅表性胃炎;LGIN:胃低级别上皮内瘤变;HGIN:胃高级别上皮内瘤变;EGC:早期胃癌;AGC:进展期胃癌;*CSG与非CSG(LGIN、HGIN、EGC和AGC)相比,P=0.001 -
[1] Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumours of the digestive system[M]. World Health Organization, 2010. [2] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide:sources, methods and major patterns in GLOBOCAN 2012[J].Int J Cancer, 2015, 136:E359-E386. doi: 10.1002/ijc.29210/pdf [3] Meng FS, Zhang ZH, Wang YM, et al. Comparison of endoscopic resection and gastrectomy for the treatment of early gastric cancer:a meta-analysis[J].Surg Endosc, 2016, 30:3673-3683. http://europepmc.org/abstract/MED/26659235 [4] Kim DY, Hong SJ, Cho GS, et al. Long-term efficacy of endoscopic submucosal dissection compared with surgery for early gastric cancer:a retrospective cohort study[J].Gut Liver, 2014, 8:519-525. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164255/ [5] Wang Y, Guan X, Fok KL, et al. A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis[J].Cell Mol Life Sci, 2008, 65:3822-3829. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=444a390aa1556436aca1230258e7a9a0 [6] Wan C, Fu J, Wang Y, et al. Exosome-related multi-pass transmembrane protein TSAP6 is a target of rhomboid protease RHBDD1-induced proteolysis[J].PLoS One, 2012, 7:e37452. http://pubmedcentralcanada.ca/pmcc/articles/PMC3356283/?lang=fr [7] Song W, Liu W, Zhao H, et al. Rhomboid domain contai-ning 1 promotes colorectal cancer growth through activation of the EGFR signalling pathway[J].Nat Commun, 2015, 6:8022. http://europepmc.org/articles/PMC4560765/ [8] Zhang M, Miao F, Huang R, et al. RHBDD1 promotes colorectal cancer metastasis through the Wnt signaling pathway and its downstream target ZEB1[J].J Exp Clin Cancer Res, 2018, 37:22. doi: 10.1186/s13046-018-0687-5 [9] Zhang X, Zhao Y, Wang C, et al. Rhomboid domain-containing protein 1 promotes breast cancer progression by regulating the p-Akt and CDK2 levels[J].Cell Commun Signal, 2018, 16:65. doi: 10.1186/s12964-018-0267-5 [10] 于航, 杨爱明, 陆星华.长链非编码RNA及其在胃癌中的作用[J].协和医学杂志, 2015, 6:146-149. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=xhyx201502015 [11] Freeman M. The rhomboid-like superfamily:molecular mechanisms and biological roles[J].Annu Rev Cell Dev Biol, 2014, 30:235-254. http://www.ncbi.nlm.nih.gov/pubmed/25062361 [12] Ren X, Song W, Liu W, et al. Rhomboid domain containing 1 inhibits cell apoptosis by upregulating AP-1 activity and its downstream target Bcl-3[J].FEBS Lett, 2013, 587:1793-1798. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=1556e493348d9549a062eee084434af0 [13] Correa P, Miller MJ. Helicobacter pylori and gastric atrophy-cancer paradoxes[J].J Natl Cancer Inst, 1995, 87:1731-1732. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=HighWire000002040593 [14] Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma[J].Nature, 2014, 513:202-209. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=4f85b068e80583bf279062804d778b9c [15] Miao F, Zhang M, Zhao Y, et al. RHBDD1 upregulates EGFR via the AP-1 pathway in colorectal cancer[J].Oncotarget, 2017, 8:25251-25260. doi: 10.18632/oncotarget.15694 [16] Slesak B, Harlozinska A, Porebska I, et al. Expression of epidermal growth factor receptor family proteins(EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis[J].Anticancer Res, 1998, 18:2727-2732. http://europepmc.org/abstract/MED/9703936 [17] Oh HS, Eom DW, Kang GH, et al. Prognostic implications of EGFR and HER-2 alteration assessed by immunohistochemistry and silver in situ hybridization in gastric cancer patients following curative resection[J].Gastric Cancer, 2014, 17:402-411. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=728e40f3d38944c742fd48e52ad42525 [18] Niu Y, Zhang J, Tong Y, et al. miR-145-5p restrained cell growth, invasion, migration and tumorigenesis via modulating RHBDD1 in colorectal cancer via the EGFR-associated signaling pathway[J]. Int J Biochem Cell Biol, 2019, 117:105641. https://www.ncbi.nlm.nih.gov/pubmed/31693935 -