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目的:采用免疫组化法检测胃癌、癌前病变和正常胃黏膜组织中鞘氨醇激酶(sphingosine kinase 1,SPHK1)和缺氧诱导因子-1α(hypoxiainduciblef actor-1α,HIF-1α)蛋白的表达,分析两者表达的差异性和相关性,并探讨两者表达与胃癌发生和转移的关系及临床病理意义。方法:检测胃癌标本254例(其中205例距癌灶边缘>5cm处取配对正常胃黏膜作为对照),慢性萎缩性胃炎43例,肠上皮化生107例及异型增生17例中SPHK1和HIF-1α蛋白的表达。结果:SPHK1蛋白在胃癌组织阳性表达率为60.6%,显著高于正常胃黏膜组织的22.0%,χ2=69.106,P<0.001;在慢性萎缩性胃炎组织中阳性表达率为41.9%,显著高于正常胃黏膜组织的22.0%,χ2=7.435,P=0.006;在肠上皮化生中阳性表达率为59.8%,显著高于正常胃黏膜组织的22.0%,χ2=44.338,P<0.001;在异型增生中阳性表达率为82.4%,显著高于正常胃黏膜组织的22.0%,Fisher确切概率法检测P<0.001。HIF-1α蛋白在胃癌组织阳性表达率为65.4%,显著高于正常胃黏膜组织的24.9%,χ2=74.564,P<0.001;在慢性萎缩性胃炎组织中阳性表达率为39.5%,显著高于正常胃黏膜组织的24.9%,χ2=3.837,P=0.050;在肠上皮化生中阳性表达率为71.0%,显著高于正常胃黏膜组织的24.9%,χ2=62.038,P<0.001;在异型增生中阳性表达率为82.4%,显著高于正常胃黏膜组织的24.9%,χ2=25.004,P=0.001。胃癌Borrmann分型中SPHK1在Ⅲ和Ⅳ型的阳性表达率为64.2%,显著高于Ⅰ和Ⅱ型的阳性表达率的42.9%,χ2=6.659,P=0.010;淋巴结转移阳性表达率为65.0%,显著高于无淋巴结转移的50.6%,χ2=4.611,P=0.032。胃癌Borrmann分型中HIF-1α蛋白在Ⅲ和Ⅳ型的阳性表达率为69.8%,显著高于Ⅰ和Ⅱ型的阳性表达率的42.9%,χ2=11.248,P=0.001;淋巴结转移阳性表达率为70.6%,显著高于无淋巴结转移的53.2%,χ2=7.154,P=0.007。胃癌组织中SPHK1和HIF-1α蛋白表达呈正相关,rk=0.302,P=0.001。结论:SPHK1和HIF-1α在胃癌和癌前病变组织中的过表达提示其在胃癌发生和转移过程中起重要的作用,两者可同成为胃癌诊断和预警转移有价值的生物标志。胃癌组织中SPHK1和HIF-1α表达的相关性提示SPHK1的过表达可能导致HIF-1α表达上调。
OBJECTIVE: To detect the expression of sphingosine kinase 1 (SPHK1) and hypoxia-inducible factor-1 alpha (HIF-1α) protein in gastric cancer, precancerous lesions and normal gastric mucosa by immunohistochemistry , Analyze the difference between the two expression and correlation, and explore the relationship between the two expression and the occurrence and metastasis of gastric cancer and clinicopathological significance. Methods: Twenty-four gastric cancer specimens (205 of which were matched to the normal gastric mucosa at a distance of> 5cm from the edge of the lesion), 43 cases of chronic atrophic gastritis, 107 cases of intestinal metaplasia and 17 cases of dysplasia were examined for SPHK1 and HIF- 1α protein expression. Results: The positive rate of SPHK1 protein in gastric cancer was 60.6%, significantly higher than that in normal gastric mucosa (χ2 = 69.106, P <0.001). The positive rate of SPHK1 protein was 41.9% in chronic atrophic gastritis The positive rate of gastric mucosa was 22.0% (χ2 = 44.338, P <0.001) in the normal gastric mucosa, which was significantly higher than that in the normal mucosa (22.0%, χ2 = 7.435, P = 0.006) The positive rate of hyperplasia was 82.4%, which was significantly higher than that of normal gastric mucosa (22.0%), Fisher exact test (P <0.001). The positive rate of HIF-1α protein in gastric cancer was 65.4%, significantly higher than that in normal gastric mucosa (χ2 = 74.564, P <0.001). The positive rate of HIF-1α protein in chronic atrophic gastritis was 39.5% The positive rate of gastric mucosa was 24.9%, χ2 = 3.837, P = 0.050. The positive rate in intestinal metaplasia was 71.0%, significantly higher than that in normal gastric mucosa (χ2 = 62.038, P <0.001) The positive expression rate in hyperplasia was 82.4%, which was significantly higher than that in normal gastric mucosa (χ2 = 25.004, P = 0.001). The positive expression rate of SPHK1 in type Ⅲ and type Ⅳ in gastric cancer Borrmann type was 64.2%, which was significantly higher than that in type Ⅰ and type Ⅱ (42.9%, χ2 = 6.659, P = 0.010). The positive rate of lymph node metastasis was 65.0% , Significantly higher than those without lymph node metastasis 50.6%, χ2 = 4.611, P = 0.032. The positive expression rate of HIF-1α protein in type Ⅲ and type Ⅳ of Borrmann’s classification of gastric cancer was 69.8%, which was significantly higher than that of type Ⅰ and type Ⅱ (42.9%, χ2 = 11.248, P = 0.001). The positive rate of lymph node metastasis Was 70.6%, significantly higher than 53.2% without lymph node metastasis, χ2 = 7.154, P = 0.007. The expression of SPHK1 and HIF-1α in gastric cancer tissues was positively correlated, rk = 0.302, P = 0.001. Conclusion: Overexpression of SPHK1 and HIF-1α in gastric cancer and precancerous lesions suggest that SPHK1 and HIF-1α play an important role in carcinogenesis and metastasis of gastric cancer. Both of them may be valuable biomarkers for diagnosis and early warning of gastric cancer. The correlation between the expression of SPHK1 and HIF-1α in gastric cancer suggests that overexpression of SPHK1 may result in the up-regulation of HIF-1α expression.