【作者】 潘凯枫； 张阳； 张联； 马峻岭； 冯国双； 关炜庠； 周彤； 李吉友； 游伟程；

【Author】 Pan Kai-Feng Zhang Yang Zhang Lian Ma Jun-Ling Feng Guo-Shuang Guan Wei-Xiang Zhou Tong Li Ji-You You Wei-Cheng Peking University School of Oncology, Beijing Institute for Cancer Research, Beijing Cancer Hospital, Beijing, 100036

【机构】 北京大学临床肿瘤学院北京市肿瘤防治研究所北京肿瘤医院；

【摘要】 目的: 通过对山东省临朐县胃癌高发区一组具有胃黏膜病理诊断的自然人群环氧化酶(COX)-2表达的检测,对其表达与胃癌癌前病变的关系及生物学相关的前列腺素(PG)E2水平、细胞增殖、凋亡、幽门螺杆菌(H．pylori) 感染状况进行全面系统的研究,为胃癌发生的机理及预防提供重要的科学依据。方法:在胃癌高发区随机选择1523例具有不同胃黏膜病理诊断的人群为研究对象,用免疫组织化学方法对胃内不同部位胃黏膜组织COX-2及Ki-67表达状况进行检测;用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)对胃黏膜组织细胞凋亡水平进行检测;用酶联免疫分析方法(EIA)对组织标本PGE2水平进行测定。结果:COX-2表达率随癌前病变的加重明显增高,由浅表性胃炎／正常(SG／N)的47．0％增至异型增生(DYS)的89．8％。以SG／N为对照,COX-2表达阳性者发生慢性萎缩性胃炎 (CAG)、肠上皮化生(IM)、不确定性异型增生(Ind DYS) 和DYS的危险性分别是COX-2不表达者的2．37(95％CI 2．10—2．67)、6．30(95％CI 5．29—7．50)、6．63(95％CI 5．54—7．94)和9．89倍(95％CI 6．04-16．20)。将COX- 2表达分为弱、中等及强阳性,发现表达强度与癌前病变的程度存在明显的等级相关。发生CAG的OR值由COX-2弱表达的2．16(95％CI 1．91-2．45)增至强阳性表达的5．36 (95％CI 3．29—8．73),IM由4．57(95％CI 3．81-5．48)增至46．36(95％CI 29．41-73．08),Ind DYS由4．44(95％CI 3．68—5．37)增至49．05(95％CI 31．02—77．56),而DYS 的OR值则由5．73(95％CI 3．42—9．59)增至113．49(95％CI 56．38—228．46)。同时,COX-2表达与H．pylori感染密切相关,两者以协同交互作用方式,共同影响胃癌癌前病变。COX-2表达阳性、同时感染H．pylori的个体与两者均阴性相比,发生CAG、IM、Ind DYS和DYS的风险分别增至13．64(95％CI 6．40—29．09)、20．72(95％CI 9．50— 45．16)、83．34(95％CI 34．10—203．79)和29．49倍(95％CI 10．82—80．42)。另外,研究还发现COX-2表达与PGE2水平存在明显的正相关,并与细胞增殖水平密切相关。结论:本研究首次在大规模人群中证明COX-2表达及表达程度与胃癌癌前病变的程度存在等级相关关系,并且COX-2表达与 H．pylori感染存在协同交互作用,共同影响胃癌癌前病变的进程。本研究结果为针对H．pylori感染和COX-2表达进行干预,以阻滞胃癌癌前病变的进展提供了重要的理论依据。更多还原

【Abstract】 Objective: To evaluate the association of COX-2 expression and precancerous gastric lesions, and its biological features, including Helicobacter pylori infection, prostaglandin (PG) E2 levels, cell proliferation-associated Ki-67 antigen expression and cell apoptosis, a cross-sectional study was conducted in a high-risk population in Linqu County, Shandong Province. Methods: A total of 1523 subjects with precancerous gastric lesions were selected at random. Expression of COX-2 and Ki-67 were detected by immunohistochemical analysis, apoptosis cells were evaluated by terminal deoxynucleotide transferase mediated dUTP nick end-labeling (TUNEL), and PGE2 levels were determined by enzyme immunoassay (EIA). Results: The prevalence of COX-2 expression varied markedly by histological status, 47.0% among those with superficial gastritis/ normal (SG/N), and 89.8% among those with dysplasia (DYS). The ORs were significantly increased for chronic atrophic gastritis (CAG, OR=2.37, 95%CI 2.10-2.67), intestinal metaplasia (IM, OR=6.30, 95%CI 5.29-7.50), indefinite dysplasia (Ind DYS, OR=6. 63,95%CI 5.54-7.94), and DYS (OR=9.89,95%CI 6.04-16.20) compared with SG/N. COX-2 expression was graded setniquantitatively at scores from 0 to 3 (0, none; 1, mild; 2, moderate; 3, severe). The ORs were increased for IM from 4.57(95% CI 3.81-5.48) at grade 1 to 46.36 (95% CI 29.41-73.08) at grade 3, Ind DYS from 4.44(95% CI 3.68-5.37) at grade 1 to 49.05 (95% CI 31.02-77.56) at grade 3, and DYS from 5.73(95% CI 3.42-9.59) at grade 1 to 113. 49 (95% CI 56.38-228.46) at grade 3. COX-2 expression was associated with H. pylori infection. Stratified analysis indicated elevated risks of advanced lesions were observed in subjects with COX-2 expression and H. pylori infection. The ORs were significantly increased for IM (OR=20.72, 95%CI 9.50-45.16), Ind DYS (OR=83.34,95%CI 34.10-203.79), and DYS (OR=29.49,95%CI 10.82-80.42) compared with SG/N. COX-2 expression was also correlated with PGE2 levels and cell proliferation. Conclusion: This study provided the strong evidence that COX-2 expression was significantly associated with precancerous gastric lesions in a high-risk population. Moreover, an interaction between COX-2 expression and H. pylori infection was observed. These findings suggest that COX-2 expression plays an important role in the progression of precancerous gastric lesions.更多还原