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1、CDH17论文：肝肠钙粘蛋白在胃癌中的表达及意义【中文摘要】检测肝肠钙粘蛋口 (CDH17)在胃癌中的表达,研究其 与胃癌临床病理参数之间的关系，分析其对胃癌术后患者预后的影响, 探索其在胃癌发生发展中的作用。方法：(1) 应用实时定量聚合酶链 反应(real-time PCR)检测69例胃癌及相应正常粘膜中CDH17 mRNA 的表达。(2)应用Western blot技术检测69例胃癌及相应止常粘膜 中CDH17蛋白的表达。(3).应用组织芯片(tissue microarray, TMA) 技术和免疫组织化学方法检测264例胃癌、正常粘膜及104例转移淋 巴结中CDH17的表达。(4)
2、应用Kappa 一致性检验方法检测CDH17在 mRNA与蛋白水平表达的关系；利用x 2检验、校止x 2检验或Fisher 精确概率法检验CDH17蛋白表达与临床病理参数之间的相关性；通过 单因索及多因索统计分析方法研究CDH17蛋白过表达对胃癌术后患 者预后的影响。结果：(1). Real-time PCR结果显示：69例胃癌样本 中，46例(66. 67%, 46/69)胃癌组织CDH17 mRNA表达较止常粘膜上调2 倍以上(2. 23-65. 34倍)，差距有统计学意义(P001)。(2). Western blot结果显示：69例胃癌样本中，47例(6& 12%, 43/69)肿瘤组
3、织 CDH17蛋口较其配对正常组织表达上调；CDH17的表达在蛋口水平与 mRNA水平显示了较强的一致性(P=0. 000, Kappa=0. 769)。(3) 免疫 组织化学结果显示：CDH17蛋白定位于胃癌细胞胞膜；CDH17蛋白在 胃癌组织阳性率(63. 26%, 167/264)高于正常粘膜(9. 85%, 26/264),差 距有统计学意义(卩0001) ； 104例转移淋巴结组织中CDH17的阳性率为81. 73%(85/104),显著高于原发癌和疋常粘膜(P0. 001) (4)CDH17蛋白表达与胃癌临床病理参数的关系：CDH17蛋 口表达上调与UICC分期(P001)、浸润深
4、度(P0.05)、淋巴结转移 (P0. 01)及远处转移(P0. 05)密切相关。CDH17蛋白在III、IV期组织 表达阳性率(73. 55% 89/121)高于I、I期(54. 55% 78/143),两者差 异有统计学意义(P0.01)；淋巴结转移组CDH17蛋白表达阳性率 (70. 95% 105/148)高于未转移组(53. 45%62/116),两者差异有统计学 意义(P0.01) (5).CDH17蛋白表达与术后患者预后的关系：随访结果 显示,CDH17阳性患者总体生存率与无瘤生存率均显著降低(P0 01)； CDH17阳性患者远处转移或复发风险相对阴性患者增加近5倍。多变 量统
5、计分析表明,CDH17是影响总体生存(HR 1.97； 95%CI 1.39-4.28； P0. 05)和无瘤生存(HR 1. 32； 95%CI0.62-3. 25； P0. 05)的独立预后 因索。排除分期影响后，11、III期胃癌患者中,CDH17阳性患者复发风 险显著高于阴性患者(P0.01)o结论：CDH17蛋口表达上调与临床分 期、浸润深度、淋巴结转移及远处转移密切相关，提示其参与了胃癌 的侵袭和转移，在胃癌发生发展过程中起到促进作用；CDH17可作为 一个新的胃癌标记物，预测II、III期冒癌患者根治术后复发的可能， 对于胃癌的诊断、预后评估和治疗具有重要的研究价值。【英文摘要】
6、:To investigate the expressiom of liver-intestine cadherin(CDH17) in gastric cancer and its association with clinicopathological parameters To explore the effect of CDH17 upon prognosis in gastric cancer and its role in carcinogenesi s and progression of thedisease .Methods:(1). CDH17 mRNA expressio
7、n was detected in 69 cases of gastric cancer and adjace nt normal mucosa by real-time polymerase chain reaction(PCR)(2). In the above-mentioned cases, protein 1evels of CDH17 were analyzed using Western blot(3). CDH17 protein expression was detected by immunohistochemistry on tissue microarray, whic
8、h containing 264 samples of primary gastric cancer and the correspond!ng para-cancerous tissue, and 104 paired 1ymph node metastases(LNM)(4). kappa tests were used to analyze the association between CDH17 mRNA and protein expression. Chi-square (x 2) tests were used to analyze the association betwee
9、n CDH17 protein expression and cl inicopathological data The effect of CDH17 upon prognosis in gastric cancer was further evaluated using univariate and multivariate Cox regression analysesResults:( 1). Tn these 69 paired samples,46 (66.67%) analyzed samples expressed a higher level (at least a 2-fo
10、ld change) of CDH17 mRNA in gastric cancer tissue specimens than in noncancerous tissue specimens(2). According to the analysis by western blot, CDH17 protein expression was high in 47 of these cases (47/69,68 12%), which was in agreement with the findings of the qRT-PCR data The Kappa test showed t
11、hat there was a correl ati on between the express!on of bigl yean mRNA and protein (P二 0. 000, k 二 0. 769)(3). By immunohistochemistry, we found that CDH17 protein was localized in the plasma membrane of gastric cancer cells and CDH17 was up-regulated in gastric cancer compared with paired nomal gas
12、tric mucosa(P0.001). Inininoreactivity of CDH17 was significantly higher in LNM than in primary gastric cancer and normal mucosa(P0.001). (4). Association between CDH17 protein expression and cl ini copathologic factors in gastric cancer:The up-regulation of CDH17 in gastric cancer was correlated wi
13、th clinical stage(P0. 01), invasion depth(P0. 01), LNM(P0. 01), distant metastasis(P0.05). Following the developing of UICC stage, the expression of CDH17 protein was increasing subsequently. Among the samples with lymph node metastasis, 105 of 148 (70. 95%) were positive compared with the samples w
14、ithout lymph node metastasis, of which 62 of 116 samples (53.45%) were positive(卩0.01). (5). Association of CDH17 protein expression with prognosis of patients with gastric cancer: Both overall survival(OS) and disease free survival(DFS) of gastric cancer patients with high expression of CDH17 were
15、decreased significantly during the follow-up period (P0.01). PositiveCDH17 expression was associated with a nearly 5-fold increasedri sk of di stant metastaseshazard ratio (HR) 4.67; 95%confidence interval(CI) 1. 76-14.73; P001 On multivariate analysis, CDH17 was an independent prognostic factor for
16、 OS (HR1.97; 95%CI 1.39-4.28; P0. 05)and DFS(HRL32; 95% CI 0.62-325; P0.05). Tumours with positive CDH17 expression were at greater risk for tumour recurrence in the patients of stage II andllldisease (P0. 01). Conclusion:The up-regulation ofCDH17 in gastric cancer was correlated with clinical stage, invasion depth, LNM, di stant metastasis, which showed thatCDH17 may participate in tumor invasion and metastasis and play a
