RhoC与CD44v6在肝细胞癌中的表达及其临床意义
摘要
目的研究RhoC与CD44v6蛋白在肝细胞癌中的表达情况并探讨其与肝细胞癌的发展中的作用及与肝细胞癌侵袭、转移和预后的关系。并研究RhoC与CD44v6二者在肝细胞癌中表达的相关性。
方法应用S-P免疫组化方法检测51例肝细胞癌及对应的癌旁组织中的RhoC与CD44v6的表达情况。
结果1.在51例肝癌中RhoC蛋白染色阳性信号呈棕黄或棕褐色,主要定位于细胞浆。CD44v6蛋白染色阳性信号呈棕黄色,主要位于细胞膜,少量在细胞质表达。RhoC蛋白在肝细胞癌及癌旁组织中的阳性表达率分别为86.27%、58.82% (P<0.01), CD44v6蛋白在肝细胞癌及癌旁组织中的阳性表达率分别为54.90 %、13.73 %;RhoC与CD44v6蛋白在肝癌组织中均明显高于在对照组癌旁组织中的表达率,统计学分析有显著差异(P<0.01)。2.在51例肝细胞癌病例中RhoC和CD44v6在Edmondson病理分级III-IV级中的阳性表达率高于I-II级的肝癌组织,在多结节肝癌中阳性表达率高于单结节的肝癌组织,在伴有淋巴结转移的肝癌中的表达率高于无淋巴结转移的肝癌组织,在伴有门静脉侵犯的肝癌组织中的阳性表达率高于无门静脉侵犯的肝癌组织,均存在显著性差异(P均<0.05);而RhoC和CD44v6的表达与性别、年龄、肿瘤直径大小、AFP表达水平、有无HBV感染无关(P均﹥0.05)。3. RhoC阴性组的中位无瘤生存时间36.94个月,阳性组中位无瘤生存时间为16.92个月;CD44v6阴性组的中位无瘤生存时间25.89个月,阳性组的中位无瘤生存时间14.93个月;对肝癌患者术后无瘤生存期进行分析,从生存曲线看,RhoC阴性表达者无瘤生存时间明显较RhoC阳性表达者长,CD44v6阴性表达者无瘤生存时间明显较CD44v6阳性表达者长。4.在肝癌组织中CD44v6阳性表达的28例中RhoC全部阳性表达,阳性率达100%,在23例CD44v6阴性表达中RhoC阳性表达16例,阳性率69.57% (16/23); RhoC的表达在肝细胞癌中与CD44v6的表达呈明显的正相关(P<0.001)。
结论RhoC与CD44v6的表达在肝细胞癌中同时存在,二者的表达参与了肝细胞癌的侵袭和转移,RhoC与CD44v6蛋白的检测对评估肝细胞癌侵袭、转移能力和预后具有重要意义。
Objective To study the expression of RhoC and CD44v6 in the progression of hepatocellular carcinama, and the relationship between the expression of them and invasion, metastasis and prognosis.And to study the relationship of the expression of RhoC and CD44v6.
Methods The expression of RhoC and CD44v6 in 51 cases of hepatocellular carcinoma were examined with S-P immunohistochemical technique.
Results The positive rate of RhoC expression in hepatocellular carcinoma and tumor-adjacent was 86.27%、58.85%, respectively (P<0.01); The positive rate of CD44v6 expression in hepatocellular carcinoma and tumor-adjacent was 54.90%、13.73%, respectively(P<0.01)。2. In 51 cases of hepatocellular carcinoma, the significant correlation was observed between high RhoC expression and pathological grade, Mass amount, metastasis and Portal vein invasion (P<0.05),and no difference could be found between RhoC expression and sex, age of patients, size of tumor, the level of AFP and HBV (P>0.05); The significant correlation was observed between high CD44v6 expression and pathological grade, Mass amount, metastasis and Portal vein invasion (P<0.05), and no difference could be found between CD44v6 expression and sex, age of patients, size of tumor, the level of AFP and HBV (P>0.05). 3. The median survival time in negative group of RhoC protein was 36.94 months and the positive one was 16.92 months . The survival rate of patients with negative RhoC expression was significantly higher than that of patients with positive expression (P<0.05); The median survival time in negative group of CD44V6 protein was 25.89 months and the positive one was 14.93 months . The survival rate of patients with negative CD44v6 expression was significantly higher than that of patients with positive expression (P<0.05); 4. The positive rate of RhoC expression was 100%(28/28) in 28 cases of positive CD44v6 expression; The positive rate of RhoC expression was 69.57 % (16/23) in 23 cases of negative CD44v6 expression. In hepatocellular carcinama, RhoC expression was positive cor- relation with CD44v6 expression(P<0.01).
Conclusion The expression of RhoC and CD44v6 may be linked with invasion and metastasis. Determination of RhoC and CD44v6 will help in predicting tumor metastatic potential and prognosis of patients with hepatocellular carcinama.
方法应用S-P免疫组化方法检测51例肝细胞癌及对应的癌旁组织中的RhoC与CD44v6的表达情况。
结果1.在51例肝癌中RhoC蛋白染色阳性信号呈棕黄或棕褐色,主要定位于细胞浆。CD44v6蛋白染色阳性信号呈棕黄色,主要位于细胞膜,少量在细胞质表达。RhoC蛋白在肝细胞癌及癌旁组织中的阳性表达率分别为86.27%、58.82% (P<0.01), CD44v6蛋白在肝细胞癌及癌旁组织中的阳性表达率分别为54.90 %、13.73 %;RhoC与CD44v6蛋白在肝癌组织中均明显高于在对照组癌旁组织中的表达率,统计学分析有显著差异(P<0.01)。2.在51例肝细胞癌病例中RhoC和CD44v6在Edmondson病理分级III-IV级中的阳性表达率高于I-II级的肝癌组织,在多结节肝癌中阳性表达率高于单结节的肝癌组织,在伴有淋巴结转移的肝癌中的表达率高于无淋巴结转移的肝癌组织,在伴有门静脉侵犯的肝癌组织中的阳性表达率高于无门静脉侵犯的肝癌组织,均存在显著性差异(P均<0.05);而RhoC和CD44v6的表达与性别、年龄、肿瘤直径大小、AFP表达水平、有无HBV感染无关(P均﹥0.05)。3. RhoC阴性组的中位无瘤生存时间36.94个月,阳性组中位无瘤生存时间为16.92个月;CD44v6阴性组的中位无瘤生存时间25.89个月,阳性组的中位无瘤生存时间14.93个月;对肝癌患者术后无瘤生存期进行分析,从生存曲线看,RhoC阴性表达者无瘤生存时间明显较RhoC阳性表达者长,CD44v6阴性表达者无瘤生存时间明显较CD44v6阳性表达者长。4.在肝癌组织中CD44v6阳性表达的28例中RhoC全部阳性表达,阳性率达100%,在23例CD44v6阴性表达中RhoC阳性表达16例,阳性率69.57% (16/23); RhoC的表达在肝细胞癌中与CD44v6的表达呈明显的正相关(P<0.001)。
结论RhoC与CD44v6的表达在肝细胞癌中同时存在,二者的表达参与了肝细胞癌的侵袭和转移,RhoC与CD44v6蛋白的检测对评估肝细胞癌侵袭、转移能力和预后具有重要意义。
Objective To study the expression of RhoC and CD44v6 in the progression of hepatocellular carcinama, and the relationship between the expression of them and invasion, metastasis and prognosis.And to study the relationship of the expression of RhoC and CD44v6.
Methods The expression of RhoC and CD44v6 in 51 cases of hepatocellular carcinoma were examined with S-P immunohistochemical technique.
Results The positive rate of RhoC expression in hepatocellular carcinoma and tumor-adjacent was 86.27%、58.85%, respectively (P<0.01); The positive rate of CD44v6 expression in hepatocellular carcinoma and tumor-adjacent was 54.90%、13.73%, respectively(P<0.01)。2. In 51 cases of hepatocellular carcinoma, the significant correlation was observed between high RhoC expression and pathological grade, Mass amount, metastasis and Portal vein invasion (P<0.05),and no difference could be found between RhoC expression and sex, age of patients, size of tumor, the level of AFP and HBV (P>0.05); The significant correlation was observed between high CD44v6 expression and pathological grade, Mass amount, metastasis and Portal vein invasion (P<0.05), and no difference could be found between CD44v6 expression and sex, age of patients, size of tumor, the level of AFP and HBV (P>0.05). 3. The median survival time in negative group of RhoC protein was 36.94 months and the positive one was 16.92 months . The survival rate of patients with negative RhoC expression was significantly higher than that of patients with positive expression (P<0.05); The median survival time in negative group of CD44V6 protein was 25.89 months and the positive one was 14.93 months . The survival rate of patients with negative CD44v6 expression was significantly higher than that of patients with positive expression (P<0.05); 4. The positive rate of RhoC expression was 100%(28/28) in 28 cases of positive CD44v6 expression; The positive rate of RhoC expression was 69.57 % (16/23) in 23 cases of negative CD44v6 expression. In hepatocellular carcinama, RhoC expression was positive cor- relation with CD44v6 expression(P<0.01).
Conclusion The expression of RhoC and CD44v6 may be linked with invasion and metastasis. Determination of RhoC and CD44v6 will help in predicting tumor metastatic potential and prognosis of patients with hepatocellular carcinama.
引文
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[2] Kato T,Hashikabe H,Iwata C,et al.Statin blocks Rho/Rho-kinase signaling,and disrupts the actin cytoskeleton:relationship to enhancement of LPS-mediated nitric oxide synthesis in vascular smooth muscle cells[J].Biochim Biophys Acta,2004,1689:267-272.
[3] Wettschureck N,Offermanns S.Rho/Rho-kinase mediated signaling in physiology and pathophysiology[J].J Mol Med,2002,80(10):629-638.
[4] Kimura K,Ito M,Amano M,et al.Reagulation of myosin phosphatase by Rho and Rho-associated inase (Rho-Kinase) [J]. Science, 1996, 273(5272): 245-248.
[5].Pan Y,Bi F,Liu N,et al.Expression of seven main Rho family members in gastriccarcinoma[J].Biochem Biophys Res Commun,2004,315(3):686-691.
[6] Liu N,Bi F,Pan Y,et al.Reversal of the malignant phenotype of gastric cancer cells by inhibition of RhoA expression and activity[J].Clin Cancer Res,2004,10(18P): 6239-6247.
[7] Clark EA, Golub TR,Lander ES , et al. Genomic analysis ofmetastasis reveals an essential role for RhoC [ J ]. N ature, 2000, 406(6795) : 532-535.
[8] Zalcman G,Closson V ,Linares2Cruz G, et al . Regulation of Ras2related RhoB protein expression during the cell cycle [J ] . Oncogene, 1995, 10(10): 1935-1945.
[9] Kaibuchi K, Kuroda S ,Amano M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells[J ] . Annu Rev Biochem,1999 ,68 (2) :459-486.
[10] Oxford G, Theodorescu D. Ras superfamily monomeric G p roteins in carcinoma cell motility [ J ]. Cancer Letters, 2003, 189 ( 2 ) : 117-128.
[11] Wang W, Yang LY, Huang GW, et al. Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinama with poor prognosis[ J ]. B r J Cancer, 2004, 90 (12) : 2349-2355
[12] WangW, Yang LY, Yang ZL, et al. Exp ression and significance of RhoC gene in hepatocellullar carcinoma[ J ]. W ould J Gastroenterol,2003, 9 (9) : 1950-1953.
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