鞘氨醇激酶1和核因子κB p65在结肠癌中的表达及其临床意义

The expression and clinical significance of SphK1 and nuclear factor-κB p65 in human coloncarcinoma

目的探讨鞘氨醇激酶1（SphKl）和NF-κB在结肠癌组织中的表达及其临床意义。方法采用免疫组化sP法、Western blot法和半定量RT-PCR法，检测66例结肠癌、癌旁及正常结肠黏膜组织中SpbKl和NF-κB的蛋白及mRNA表达。结果RT-PCR结果显示，66例结肠癌组织中SphKl和NF-κBmRNA阳性表达率分别为84．85％（56／66）和74．24％（49／66），Westernblot结果显示其SphKl和NF-κB蛋白阳性表达率分别为78．79％（52／66）和69．70％（46／66），均高于癌旁[mRNA：63．64％（42／66），48．49％（32／66）；蛋白：57．58％（38／66），45．45％（30／66）]和正常黏膜组织[mRNA：42．42％（28／66），25．76％（17／66）；蛋白：36．36％（24／66），24．24％（16／66）]，P值均〈0．05。结肠癌组织中SphKl和NF-κB的mRNA及蛋白的相对表达水平均高于癌旁及正常结肠黏膜组织（mRNA：0．554-0．06比0．354-0．05比0．25±0．05，0．75±0．06比0．434-0．05比0．304-0．04：蛋白：0．774-0．05比0．384-0．06比0．124-0．03，0．454-0．08比0．23±0．05比0．134-0．03；p值均〈0．05）。SphKl和NF-κB表达之间存在明显相关性（r=0．459，P=0．036）。免疫组化结果与前述较为一致。SphKl和NF-κB在癌组织中的高表达水平与肿瘤浸润程度、有无远处转移、淋巴结转移、临床分期有关（P值均〈0．05）。SphKl的高表达水平还与组织分化程度有关（P〈0．05）。结论SphKl和NF-κB可能与结肠癌的发生、发展密切相关，并可能在结肠癌的浸润和转移中起重要作用。

Objective To investigate the expression of sphingosine kinase 1 （ SphK1 ） and NF-κB in colon carcinoma tissues and their correlation with clinicopathologic features. Methods Sixty-six paraffin- embedded colon carcinoma samples and 66 fresh colon carcinoma samples were tested using immunohistoehemistry, RT-PCR and Western blot, respectively. Results In 66 fresh colon carcinoma samples, the positive rate of SphK1 and NF-κB mRNA expression were 84. 85% （56/66） and 74. 24% （49/66） , while the positive rate of SphK1 and NF-κB protein detected by Western blot were 78.79% （52/66） and 69. 70% （46/66）. The positive rates were higher than those in the adjacent tissues [ mRNA： 63.64% （42/66） ,48.49% （32/66） ;protein：57.58% （38/66） ,45.45% （30/66） ] and the normal mucosa [ mRNA：42. 42% （ 28/66 ）, 25.76% （ 17/66 ） ; protein： 36. 36% （ 24/66 ）, 24. 24% （ 16/66 ） ], with statistical significances （ all P values 〈 0. 05 ）. The mean expressive levels of SphK1 and NF-κB mRNA and protein in colon carcinoma were both significantly higher than those in the adjacent tissues and the normal mucosa （mRNA： 0.55±0.06 vs0.35 ±0.05 vs0.25±0.05, 0.75±0.06 vs0.43±0.05 vsO. 30± 0.04; protein： 0.77±0.05 vs0.38±0.06vsO. 12±0.03, 0.45±0.08 vs0.23±0.05 vs0.13±0.03; all P values 〈 0. 05 ）. There was a close correlation between SphK1 and NF-κB expression levels （ r = 0. 459, P = 0. 036）. The results of immunohistochemistry were similar to those of RT-PCR and Western blot. Overexpression of SphK1 and NF-κB in colon carcinoma was related with depth of invasion, distant and lymph node metastasis and Dukes＇stages （all P values 〈 0. 05）. The expression of SphK1 was also relatedwith differentiation （P 〈 0. 05）. Conclusions Overexpression of SphK1 and NF-κB may be involved in the pathogenesis and progression of colon carcinoma. Moreover, SphK1 and NF-κB may be correlated with the invasion and metastasis of colon carcinoma.