Ogawa J I, Inoue H, Koide S
First Department of Surgery, School of Medicine, Tokai University, Japan.
Cancer. 1997 May 1;79(9):1678-85. doi: 10.1002/(sici)1097-0142(19970501)79:9<1678::aid-cncr7>3.0.co;2-8.
Biosynthesis of sialyl Lewis(x) (sLe(x)) requires a sialyltransferase for alpha-2,3-sialylation and a fucosyltransferase for alpha-1,3-fucosylation. To date, five human alpha-1,3-fucosyltransferase (Fuc-T) genes and five human alpha-2,3-sialyltransferase (ST) genes have been cloned. However, it is not known which enzyme is mainly responsible for sLe(x) synthesis.
Three hundred thirteen patients with nonsmall cell lung carcinoma who had a curative tumor resection were the subjects of this study. Using tumor tissues fixed in formaldehyde, amplification of genomic DNA of Fuc-T and ST was performed by PCR and correlated with sLe(x) staining and patient prognosis.
The frequency of strong ST3N and Fuc-TVII amplification was significantly higher than that of STZ, ST4, Fuc-TIII, Fuc-TV, and Fuc-TVI amplification (P < 0.01). The frequency of sLe(x) staining was similar to ST3N and Fuc-TVII amplification. Survival of the patients whose tumors had strong amplification of both ST3N and Fuc-TVII was significantly shorter than that of patients whose tumors had no amplification of either gene (P < 0.01). In a multivariate analysis of survival, Fuc-TVII remained a statistically significant prognostic factor.
In lung carcinoma, ST3N and Fuc-TVII may both be related to sLe(x) synthesis, and Fuc-TVII is a more important indicator of poor prognosis.
唾液酸化路易斯寡糖x(sLe(x))的生物合成需要一种用于α-2,3-唾液酸化的唾液酸转移酶和一种用于α-1,3-岩藻糖基化的岩藻糖基转移酶。迄今为止,已克隆出5个人类α-1,3-岩藻糖基转移酶(Fuc-T)基因和5个人类α-2,3-唾液酸转移酶(ST)基因。然而,尚不清楚哪种酶主要负责sLe(x)的合成。
本研究以313例行根治性肿瘤切除术的非小细胞肺癌患者为研究对象。利用甲醛固定的肿瘤组织,通过聚合酶链反应(PCR)对Fuc-T和ST的基因组DNA进行扩增,并与sLe(x)染色及患者预后相关联。
ST3N和Fuc-TVII强扩增的频率显著高于STZ、ST4、Fuc-TIII、Fuc-TV和Fuc-TVI的扩增频率(P<0.01)。sLe(x)染色频率与ST3N和Fuc-TVII扩增相似。肿瘤同时有ST3N和Fuc-TVII强扩增的患者的生存期显著短于肿瘤这两个基因均无扩增的患者(P<0.01)。在生存期的多因素分析中,Fuc-TVII仍然是一个具有统计学意义的预后因素。
在肺癌中,ST3N和Fuc-TVII可能均与sLe(x)合成有关,且Fuc-TVII是预后不良的一个更重要指标。