Mitra P, Shibuta K, Mathai J, Shimoda K, Banner B F, Mori M, Barnard G F
Division of Digestive Disease and Nutrition, University of Massachusetts Medical Center, Worcester, MA 01655, USA.
Int J Oncol. 1999 May;14(5):917-25. doi: 10.3892/ijo.14.5.917.
We have recently demonstrated by Northern blot and RT-PCR that the mRNA expression of the alpha-chemokine hIRH/SDF-1alpha is reduced in hepatocellular carcinoma (HCC), several digestive tract cancers and premalignant colon adenomas, and that its receptor CXCR4 mRNA expression is reduced in HCC. Here we investigate the expression of CXCR4 mRNA expression in several digestive tract cancers and hepatitis C viral (HCV) infected liver, a premalignant condition. There was no difference in the CXCR4 mRNA expression in colon, esophageal or gastric cancers compared to non-cancerous tissues. This is significantly different from the reduced expression we have seen with hepatocellular carcinoma (p<0.05). To better refine regional tumor or hepatic cytokine mRNA analysis within a biopsy sample we describe a micro-isolation technique for RNA extraction from portal and triad areas of liver biopsies or other small malignant or non-malignant biopsy samples suitable for use in RT-PCR and differential display reactions. In HCV liver biopsies, the expression of hIRH and its receptor CXCR4 mRNA, corrected for G3PDH, was not significantly different from that of control non-HCV (steatosis) biopsies. CXCR4 is expressed on leukocytes and its expression was predicted to correlate with hepatic inflammation. CXCR4 receptor mRNA expression did correlate significantly with that of its ligand hIRH/SDF-1alpha (p=0.001), and with the severity of fibrosis (p<0.05), but not with portal inflammation (p<0.10), piecemeal necrosis (p<0.10), lobular inflammation (p>0.10), the presence of lymphoid aggregates (p>0.10), or the total histological activity index (p=0.07). There was no difference in expression of hIRH or CXCR4 between responders and non-responders to interferon (IFN) treatment, while as a control, the responder group of patients did show a higher expression of IFNalpha receptor than the non-responder group (p=0.05).
我们最近通过Northern印迹法和逆转录聚合酶链反应（RT-PCR）证明，α-趋化因子hIRH/SDF-1α的mRNA表达在肝细胞癌（HCC）、几种消化道癌症和癌前结肠腺瘤中降低，并且其受体CXCR4 mRNA表达在HCC中降低。在此，我们研究CXCR4 mRNA表达在几种消化道癌症以及丙型肝炎病毒（HCV）感染的肝脏（一种癌前状态）中的情况。与非癌组织相比，结肠癌、食管癌或胃癌中的CXCR4 mRNA表达没有差异。这与我们在肝细胞癌中观察到的表达降低显著不同（p<0.05）。为了在活检样本中更好地优化区域肿瘤或肝脏细胞因子mRNA分析，我们描述了一种微分离技术，用于从肝活检的门静脉和三联区或其他适用于RT-PCR和差异显示反应的小的恶性或非恶性活检样本中提取RNA。在HCV肝活检中，经甘油醛-3-磷酸脱氢酶（G3PDH）校正后，hIRH及其受体CXCR4 mRNA的表达与对照非HCV（脂肪变性）活检没有显著差异。CXCR4在白细胞上表达，并且预计其表达与肝脏炎症相关。CXCR4受体mRNA表达确实与其配体hIRH/SDF-1α的表达显著相关（p=0.001），并且与纤维化的严重程度相关（p<0.05），但与门静脉炎症（p<0.10）、桥接坏死（p<0.10）、小叶炎症（p>0.10）、淋巴滤泡的存在（p>0.10）或总组织学活动指数（p=0.07）无关。在干扰素（IFN）治疗的应答者和非应答者之间，hIRH或CXCR4的表达没有差异，而作为对照，应答者组患者的IFNα受体表达确实高于非应答者组（p=0.05）。
