Department of Anorectal Surgery and Colorectal Cancer Center, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Dig Dis. 2013 Aug;14(8):417-24. doi: 10.1111/1751-2980.12060.
To determine the hedgehog (Hh) signaling pathway correlated with the development of colon cancer and melanosis coli.
Protein and mRNA levels of Hh signaling pathway components (sonic hedgehog [Shh], protein patched homolog 1 [Ptch 1], GLI family zinc finger 1 [Gli 1] and suppressor of fused homolog [Drosophila] [Sufu]) in 127 patients with colon cancer, 36 with melanosis coli and 20 adjacent normal mucosal tissues taken from surgical specimens were evaluated using antibody staining and quantitative real-time polymerase chain reaction.
In adjacent normal tissue Shh and Ptch1, but not Gli1 or Sufu, were weakly expressed and mainly in the lining epithelium of the colonic mucosa. In cancerous tissues Shh and Gli1 were uniformly strong while Ptch1 was patchy and weak, and Sufu uniformly weak, which paralleled their levels of corresponding mRNA. Elevated protein levels of Shh and Ptch were significantly associated with mucinous colonic tissues. Elevated Sufu protein levels were positively correlated with the diameter and invasion of the tumor. In patients with melanosis coli, mRNA levels of Shh, Ptch1, Gli1 and Sufu were very low, which was similar to those of adjacent normal tissues; but protein levels of Shh, Ptch1 and Gli1, but not Sufu, were high, which was similar to those of cancerous tissues.
The mRNA and protein levels of Hh pathway components are aberrantly elevated in colon cancer, which may be the potential molecular classification markers. Further studies are required to determine the role of melanosis coli in the colon tumorigenesis.
确定与结肠癌和结肠黑变病发展相关的刺猬(Hh)信号通路。
采用抗体染色和实时定量聚合酶链反应检测 127 例结肠癌患者、36 例结肠黑变病患者和 20 例手术标本相邻正常黏膜组织中 Hh 信号通路成分( sonic hedgehog [Shh]、protein patched homolog 1 [Ptch 1]、GLI 家族锌指蛋白 1 [Gli 1]和 suppressor of fused homolog [Drosophila] [Sufu])的蛋白和 mRNA 水平。
在相邻正常组织中,Shh 和 Ptch1 蛋白表达较弱,主要位于结肠黏膜的衬里上皮,而 Gli1 和 Sufu 蛋白则不表达或表达较弱。在癌组织中,Shh 和 Gli1 蛋白均匀强表达,而 Ptch1 蛋白呈斑片状和弱表达,Sufu 蛋白均匀弱表达,这与其相应 mRNA 的水平一致。Shh 和 Ptch 蛋白水平升高与黏液性结肠组织显著相关。Sufu 蛋白水平升高与肿瘤直径和侵袭呈正相关。在结肠黑变病患者中,Shh、Ptch1、Gli1 和 Sufu 的 mRNA 水平非常低,与相邻正常组织相似;但 Shh、Ptch1 和 Gli1 蛋白水平升高,与癌组织相似。
Hh 通路成分的 mRNA 和蛋白水平在结肠癌中异常升高,可能是潜在的分子分类标志物。需要进一步研究结肠黑变病在结肠肿瘤发生中的作用。