【摘要】 目的本研究探讨胃癌组织及对应的癌旁正常组织中Sfrp5基因甲基化修饰及蛋白表达与临床病理参数的关系并探讨其临床意义。方法选择外科手术切除并病理证实为胃癌的新鲜癌组织及其新鲜癌旁正常组织各90例,每例患者均在胃癌原发病变区和切除标本距离切缘大于5 cm处(正常未发生癌变)分别取材;新鲜组织置于液氮罐中暂存,另外一块组织经中性甲醛固定,经脱水、透明制成蜡块,切片、常规HE染色切片经临床病理科医生的观察保证取材的准确性。所有患者术前均未经化疗和放疗,均有完整的临床和病理资料。不符合上述条件的标本被排除于研究之外。甲基化特异性PCR测定患者癌组织及正常组织中Sfrp5基因发生甲基化的状况,用免疫组织化学(Envision)法检测Sfrp5蛋白的表达情况。结果 Sfrp5蛋白在胃癌和癌旁正常组织中的阳性表达率分别为20%(18/90)和90%(81/90),2组差异有统计学意义(P<0.05)。Sfrp5基因在癌组织及癌旁组织中的甲基化频率分别为82.2%(74/90)和18.9%(17/90),差异有统计学意义(P<0.05);Sfrp5基因甲基化频率在无淋巴结转移组[66.7%(22/33)]显著低于有淋巴结转移组[86.0%(49/57)],差异有统计学意义(P<0.05);高中分化组中Sfrp5基因的甲基化频率为71.4%(25/35),低分化组的甲基化率为81.8%(45/55),但2组间差异无统计学意义(P>0.05);≥50岁年龄组基因甲基化频率[84.5%(71/84)]低于≤50岁年龄组[100%(6/6)],女性组[76.4%(13/17)]甲基化频率低于男性组[76.7%(56/73)],但差异均无统计学意义(P>0.05)。结论 Sfrp5基因高甲基化是其蛋白表达降低的重要原因并且可能与胃癌的发生、发展有关。更多还原

【Abstract】 Objective To investigate the expression and clinical significance methylation modification of Sfrp5 gene in gastric cancer tissues and adjacent normal tissues,and to explore its correlation with clinical pathological parameters.Methods Ninety specimens of gastric cancer tissues which were confirmed by pathological examination and 90 cases of normal tissues adjacent to carcinoma were enrolled in the study. Among the patients with gastric cancer tissues,there were 73 males,17 females,with age arrang being 46 ～ 76 yr,and the average age being 64 yr. In the aspect of histological type,there were 35 cases of high and moderately differentiated adenocarcinoma,55 cases of poorly differentiated and undifferentiated adenocarcioma. Moreover 33 cases had lymph node metastasis and 57 cases had no lymph node metastasis. All the specimens were taken from primary tumor and normal tissues adjacent to carcinoma( more than 5 cm away from the cut edge). The specimens were frozened in liquid nitrogen immediately after obtained. The specimens were treated by routine method for pathological examination. Moreover all the patients were not treated by chemotherapy and radiotherapy before surgery,with complete clinical and pathological data. The methylation status of Sfrp5 gene in cancer tissues and in adjacent normal tissues was detected by methylation specific PCR methylation,and the expression levels of Sfrp5 were detected by immunohistochemistry. Results The positive expression rate of Sfrp5 protein in gastric cancer tissues and in normal tissues adjacent to carcinoma was 20%( 18/90) and 90%( 81/90),respectively,there was significant difference between the two groups( P < 0. 05). The methylation rate of Sfrp5 gene in gastric cancer tissues and normal tissues adjacent to carcinoma was82. 2%( 74/90) and 18. 9%( 17/90),respectively,there was significant difference between the two groups( P < 0. 05).Moreover the methylation rate of Sfrp5 gene in tissues without lymph node metastasis was 66. 7%( 22/33),which was significantly lower than that [86. 0%( 49/57) ]in the tissues with lymph node metastasis( P < 0. 05). The methylation rate of Sfrp5 gene in high differentiation group was 71. 4%( 25/35),which was lower than that [81. 8%( 45/55) ] in poor differentiation group,however,there was no significant difference between the two groups( P > 0. 05). In addition the methylation rate of Sfrp5 gene was 84. 5%( 71/84) in ≥50 years group,which was 100%( 6/6) in≤50 years group,but there was no significant difference between the two groups( P > 0. 05). The methylation rate of Sfrp5 gene was 76. 4%( 13/17) in female group,which was lower than that [76. 7%( 56/73) ]in male group,but there was no significant difference between the two groups( P > 0. 0 5).C on clu sion T he high levels of Sfrp5 gene m ethylation frequency are the m ain reason of the decrease of its protein in gastric cancer tissues,which may be correlated with the pathogenesis and development of gastric cancer.更多还原