应用低密度芯片初步筛选胃癌淋巴转移相关基因的研究  

Elementary screening lymph node metastatic-related genes in gastric cancer by low-density cDNA microarray

作　　者：黄宝俊[1] 徐惠绵[1] 赵雨杰[2,3] 

机构地区：[1]中国医科大学(附属第一医院肿瘤外科),辽宁沈阳110001 [2]中国医科大学(附属第一医院 [3]生物芯片中心),辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2006年第24期1841-1845,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30370640)

摘　　要：目的:运用低密度cDNA芯片技术初步筛选影响胃癌淋巴结转移的分子标志。方法:运用自制低密度cDNA芯片检测15例胃癌患者原发癌灶和淋巴结转移癌中多个基因mRNA表达,并用RT-PCR方法进行验证,分析其与胃癌侵袭和淋巴结转移的相关性。结果:hTERT在淋巴结转移癌中表达明显高于胃原发癌灶(P= 0．001)。原发癌灶中MMP-7和Heparanase表达在小结节孤立型淋巴结病例中明显高于大结节融合型者(P值分别为0．022和0．002),而CDH1表达明显降低(P= 0．002);淋巴结转移癌灶中CDH1表达在小结节孤立型淋巴结病例中亦明显降低(P=0．046)。按淋巴结转移个数分成轻重两组(≤6个为轻度转移,≥7个为重度转移),原发癌灶中MMP-7和hTERT表达在重组明显高于轻组(P值分别为0．001和0．005);淋巴结转移癌灶中MMP-7、S100A4和hTERT基因表达在重组明显增高(P值分别为0．000 05、0．007和0．016),而nm23H1和CDH1表达明显降低(P值分别为0．013和0．001)。胃原发癌中MMP-7、Heparanase、S100A4过表达和(或)nm23H1、CDH1、KAI-1表达降低或缺失者,胃癌多侵透浆膜,且浆膜受侵面积较大。结论:hTERT、MMP-7、S100A4、Heparanase、CDH1和nm23H1基因表达与胃癌淋巴结转移关系密切,可望成为胃癌淋巴结转移诊断和治疗的分子靶点。OBJECTIVE： To screen the lymph node metastatic-related genes in human gastric cancer by the low-density eDNA microarray technique. METHODS： A total of 15 gastric cancer primary and nodal involvement lesions were examined by a low-density eDNA microarray containing 23 genes and RT-PCR was used for the further verification. The correlation between the gene expression and invasion and nodal involvement were analyzed. RERULTS： Hybridization signals had good specificity, which were seen for the house keeping genes（internal control）, but were not seen for the hepatitis B gene （negative control） and spotting solution only （blank control）. The expressions of hTERT in the nodal lesions were higher than those in the coupled primary lesions （P = 0. 001）. With respect to the number of nodal involvement, MMP-7 and hTERT expressions in the primary lesions were higher in the heavier nodal involvement group （no less than 7） than those in the lighter one （no more than 6）（P= 0.001,0. 005 respectively）. MMP-7, S100A4 and hTERT expressions in nodal lesions were higher in the heavier than those in the lighter （P = 0. 000 05, P = 0. 007, P = 0. 016, respectively）, whereas nm23H1 and CDH1 were lower（P=0. 013,P=0. 001）. With respect to the nodal type, in the primary lesions MMP-7 and Heparanase expressions in the small node isolation were higher than those in the big node fusion （P= 0. 022,0. 002 respectively）. Whereas CDH1 expression was lower （P= 0. 002）, so did CDH1 expression in nodal lesions （P = 0. 046）. In patients with MMP-7, Heparanase, S100A4 overexpressions and/or nm23H1, CDH1, KAI-1 lessexpressions or.loss in gastric enaeer primary lesions, most eases were serosa involvement and the area of serosa involvement was biggish. CONCLUSION：MMP-7, hTERT, Heparanase, CDH1 correlated closely with nodal involvement in gastric carcinomas, and may be the molecular target for an early diagnosis of nodal involvement and treatment in gastric cancer.

关 键 词：胃肿瘤/病理学 胃肿瘤/遗传学 淋巴转移 CDNA芯片 基因表达 

分 类 号：R735.2[医药卫生—肿瘤]