Guo Rui-fang, Zang Shi-zhu, Zhang Liang, Li Wen-mei, Hu Fu-lian, Lü You-yong
Department of Gastroenterology, Inner Mongolia Hospital, Hohhot 010017, China.
Zhonghua Yi Xue Za Zhi. 2006 Dec 12;86(46):3249-54.
To clarify the correlation of transforming growth factor-beta1 (TGF-beta1) expression with the differentiation and prognosis of advanced gastric cancer (GC).
Whole genome expression chip hybridization, was used to detect the expression of TGF-beta1 and TGF-betaR1 in 20 specimens of intestinal-type GC and para-cancer tissues. RT-PCR and immunohistochemistry (IHC) analysis were used to detect the mRNA and protein expression of TGF-beta1 and TGF-betaR1 in 30 specimens of intestinal-type GC tissue and para-cancer tissues. The mixture of gastric mucosa tissues from 20 non-tumor patients was used as common reference.
The expression level of TGF-beta1 and TGF-betaR-1 genes was higher in the GC tissues than in the para-cancer tissues. However, the expression of Smad gene family was not significantly different between the GC tissues and para-tumor normal tissues. TGF-beta1 gene expression and TGF-betaR1 gene expression were higher in the GC tissues. RT-PCR showed that both TGF-beta1 and TGF-betaR-1 genes were highly expressed in the mRNA level in 21 of the 30 CC patients IHC showed that TGF-beta1 protein was expressed mainly in the cytoplasm. 32 of the 90 specimens of GC tissue were highly positive in TGF-beta1 protein (64%), in comparison with the positive rate of 5% (1/20) in the para-cancer normal tissues. The TGF-beta1 protein expression rate of the highly and moderately differentiated GC tissues was 59% (59%, 23/39), significantly higher than that of the lowly differentiated GC tissues (18%, 9/51, P < 0.01). IHC showed that the TGF-beta R-I rate was 57% (42/74) in the well differentiated specimens, particularly 68% (26/38) in the highly differentiated specimens, and was 44% in the poorly differentiated GC (6/20, P < 0.05). Log rank test showed that the prognosis of the patients positive in TGF-beta1 was significantly better than those negative in TGF-beta1 (P = 0.0058). However, the survival rate did not differ significantly according to TGF-beta R-I expression (P = 0.8453).
TGF-beta1 expression is significantly correlated with the differentiation degree of GC. Moreover, positive expression of TGF-beta1 is a favorable prognostic factor in advanced GC. Expression of TGF-beta1 may be an important preoperative prognostic variable for advanced GC.
阐明转化生长因子-β1（TGF-β1）表达与进展期胃癌（GC）分化及预后的相关性。
采用全基因组表达芯片杂交技术检测20例肠型GC组织及癌旁组织中TGF-β1和TGF-βR1的表达。运用逆转录聚合酶链反应（RT-PCR）和免疫组织化学（IHC）分析检测30例肠型GC组织及癌旁组织中TGF-β1和TGF-βR1的mRNA及蛋白表达。选取20例非肿瘤患者的胃黏膜组织混合样本作为共同对照。
GC组织中TGF-β1和TGF-βR-1基因的表达水平高于癌旁组织。然而，GC组织与癌旁正常组织中Smad基因家族的表达无显著差异。GC组织中TGF-β1基因表达和TGF-βR1基因表达较高。RT-PCR显示，30例GC患者中有21例TGF-β1和TGF-βR-1基因在mRNA水平均高表达。IHC显示，TGF-β1蛋白主要表达于细胞质中。90例GC组织样本中有32例TGF-β1蛋白呈高阳性（64%），而癌旁正常组织的阳性率为5%（1/20）。高、中分化GC组织的TGF-β1蛋白表达率为59%（59%，23/39），显著高于低分化GC组织（18%，9/51，P<0.01）。IHC显示，高分化样本中TGF-βR-I率为57%（42/74），其中高分化样本尤其为68%（26/38），低分化GC组织中为44%（6/20，P<0.05）。对数秩检验显示，TGF-β1阳性患者的预后显著优于TGF-β1阴性患者（P = 0.0058）。然而，根据TGF-βR-I表达，生存率无显著差异（P = 0.8453）。
TGF-β1表达与GC的分化程度显著相关。此外，TGF-β1的阳性表达是进展期GC的一个有利预后因素。TGF-β1的表达可能是进展期GC重要的术前预后变量。
