5-脂加氧酶在胃癌中的表达与环氧化酶-2和甲酰肽受体2的关系及其临床意义

Expressions of 5-LOX in gastric carcinoma and its relationships with COX-2 and FPR2 and their clinicopathological implications

目的 探讨5-脂加氧酶(5-LOX)在胃癌中的表达与5-LOX与环氧化酶-2(COX-2)和甲酰肽受体2(FPR_(2))的关系及其临床意义。方法 采用免疫组织化学法检测70例胃癌组织中3个指标的表达情况,并分析三者间的关系以及临床病理联系。沉默5-LOX基因观察对COX-2及FPR_(2)的表达有无影响。结果 ≤45岁和>45岁患者5-LOX阳性表达率分别为76.0%和84.4%;肿块直径≤3 cm和>3 cm者阳性表达率分别为82.1%和81.0%;低分化腺癌、中-高分化腺癌和黏液腺癌阳性表达率分别为80.0%、80.0%和90.0%,组间差异均无统计学意义(P>0.05)。在无、有淋巴结转移组中5-LOX阳性率分别为71.8%和93.5%;在Ⅰ~Ⅱ、Ⅲ~Ⅳ期胃癌中5-LOX的阳性表达率分别为75.0%和95.5%,组间差异均有统计学意义(P<0.05);5-LOX在COX-2阳性和阴性病例中阳性率分别为81.6%和81.0%,组间差异无统计学意义(P>0.05);5-LOX在FPR_(2)阳性和阴性病例中阳性率分别为78.1%和84.2%,组间差异无统计学意义(P>0.05)。在SGC-7901转染实验中,沉默5-LOX基因对COX-2及FPR_(2)的表达没有影响。结论 5-LOX在胃癌的侵袭、转移过程中起重要作用,同时靶向5-LOX和COX-2有望成为治疗胃癌的有效手段。

Objective To investigate 5-lipoxygenase(5-LOX) expression in gastric carcinoma, its relationships with cyclooxygenase-2(COX-2) and formyl peptide receptor type 2(FPR_(2)), and their clinicopathological implications. Methods Expressions of the above three indexes were detected from 70 gastric carcinoma patients by immunohistochemistry. The relationships among them and clinicopathological features were analyzed. Moreover, whether knockdowning 5-LOX had effects on COX-2 and FPR_(2) mRNA expression in SGC-7901 cells was investigated.Results The positive expression rates of 5-LOX were 76.0% in cases ≤45 years and 84.4% in cases >45 years;82.1%in cases with tumor diameter ≤3 cm and 81.0% in cases with tumor diameter >3 cm;80.0%, 80.0%, and 90.0% in cases of poorly differentiated, middle-highly differentiated, and mucinous adenocarcinoma, respectively, with no significant difference(P>0.05). The positive expression rates of 5-LOX in cases of gastric carcinoma without and with axillary node metastasis were 71.8% and 93.5%;in cases at stage Ⅰ-Ⅱ and Ⅲ-Ⅳ, 75.0% and 95.5% respectively, with significant difference(P<0.05). The positive expression rates of 5-LOX in cases of gastric carcinoma with positive COX-2 expression and negative COX-2 expression were 81.6% and 81.0% resepctively, without significant difference(P>0.05), and the values in cases of gastric carcinoma with positive FPR_(2) expression and negative FPR_(2) expression were 78.1% and 84.2% respectively, without significant difference as well(P>0.05). Moreover, silencing 5-LOX had no effects on COX-2 and FPR_(2) mRNA expressions in SGC-7901 cells. Conclusion 5-LOX plays an important role in the invasion and metastasis of gastric carcinoma, and combined targeting 5-LOX and COX-2 would be an effective approach for gastric carcinoma.