Elevated Expression of Autocrine Motility Factor Receptor Correlates with Overexpression of RhoC and Indicates Poor Prognosis in Hepatocellular Carcinoma
- 144 Downloads
- 15 Citations
Abstract
Our previous study identified RhoC as an invasion and metastasis marker in hepatocellular carcinoma patients. Recent document suggested RhoGTPase is required for autocrine motility factor signaling. In this study, we questioned whether there is a correlation between expression of autocrine motility factor receptor and RhoC. Furthermore, we questioned whether elevated expression of autocrine motility factor correlates with metastasis and poor prognosis of HCC. The mRNA expression level of AMFR and RhoC were examined by RT-PCR in 25 cases of HCC and pericarcinomatous liver tissues (PCLT). In addition, the correlation between the expression level of AMFR and clinical pathologic parameters was analyzed. Furthermore, follow-up information was collected to evaluate the prognostic value of AMFR for HCC patients. Our results showed that the expression of AMFR and RhoC significantly increased in HCC compared with PCLT; extrahepatic metastatic lesions expressed significantly higher levels of AMFR and RhoC than corresponding intrahepatic HCC tissues. There is a highly significant correlation of AMFR expression levels with tumor vein invasion, number of tumor nodes, and tumor stage. Anticipatively, positive correlation was observed between mRNA expression of AMFR and RhoC gene. Furthermore, the HCC patients with high-expression of AMFR had significant high recurrence/metastasis and shorter survival than those with low-expression of AMFR. Together, our findings suggested a strong correlation between the expression of AMFR and RhoC and also a correlation between overexpression of them and invasion and metastasis of HCC. Furthermore, our data indicated AMFR as a potential prognosis for HCC.
Keywords
Hepatocellular carcinoma Gene AMFR RhoC Recurrence Metastasis PrognosisNotes
Acknowledgments
Supported by a grant from National Key Technologies R and D Program of China (No.2001BA703B04), a grant from National keystone basic research program of China (973 Program) (No. 2004CB720303) and National Science Fund for Distinguished Young Scholars of China (No. 30328028), a grant from the Ph.D. Programs Foundation of Ministry of Education of China (No. 20030533037), and Distinguished Young Scholars of Xiangya hospital CSU.
References
- 1.Tung P, Poon R, Fan ST, Wong J (2000) Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 232:10–24CrossRefGoogle Scholar
- 2.Murray CJ, Lopez AD (1997) Mortality by cause for eight regions of the world. Global Burden of Disease Study. Lancet 349:1269–1276PubMedCrossRefGoogle Scholar
- 3.Schafer DF, Sorrell MF (1999) Hepatocellular carcinoma. Lancet 353:1253–1256PubMedCrossRefGoogle Scholar
- 4.Makuuchi M, Takayama T, Kubota K, Kimura W, Midorikawa Y, Miyagawa S, Kawasaki S (1998) Hepatic resection for hepatocellular carcinoma: Japanese experience. Hepatogastroenterology 45:1267–1274PubMedGoogle Scholar
- 5.Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J (1999) Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths. Ann Surg 229:322–330PubMedCrossRefGoogle Scholar
- 6.Poon TPR, Fan ST, Wong J (2000) Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 232:10–24CrossRefGoogle Scholar
- 7.Yamaguchi H, Wyckoff J, Condeelis J (2005) Cell migration in tumors. Curr Opin Cell Biol 17:559–564PubMedCrossRefGoogle Scholar
- 8.Yamazaki D, Kurisu S, Takenawa T (2005) Regulation of cancer cell motility through actin reorganization. Cancer Sci 96:379–386PubMedCrossRefGoogle Scholar
- 9.Silletti S, Watanabe H, Hogan V, Nabi IR, Raz A (1991) Purification of B16-F1 melanoma autocrine motility factor and its receptor. Cancer Res 51:3507–3511PubMedGoogle Scholar
- 10.Watanabe H, Carmi P, Hogan V, Raz T, Silletti S, Nabi IR, Raz A (1991) Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor. J Biol Chem 266:13442–13448PubMedGoogle Scholar
- 11.Stracke ML, Guirguis R, Liotta LA, Schiffmann E (1987) Pertussis toxin inhibits stimulated motility independently of the adenylate cyclase pathway in human melanoma cells. Biochem Biophys Res Commun 146:339–345PubMedCrossRefGoogle Scholar
- 12.Tsutsumi S, Gupta SK, Hogan V, Collard JG, Raz A (2002) Activation of small GTPase Rho is required for autocrine motility factor signaling. Cancer Res 62:4484–4490PubMedGoogle Scholar
- 13.Bishop AL, Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348:241–255PubMedCrossRefGoogle Scholar
- 14.Van Aelst L, D'Souza-Schorey C (1997) Rho GTPases and signaling networks. Genes Dev 11:2295–2322PubMedGoogle Scholar
- 15.Sahai E, Marshall CJ (2002) RhoGTPases and cancer. Nat Rev Cancer 2:133–142PubMedCrossRefGoogle Scholar
- 16.Suwa H, Ohshio G, Imamura T, Watanabe G, Arii S, Imamura M, Narumiya S, Hiai H, Fukumoto M (1998) Overexpression of RhoC gene correlates with progression of ductal adenocarcinoma of the pancreas. Br J Cancer 77:147–152PubMedGoogle Scholar
- 17.Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y, Nakamura Y (2001) Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res 61:2129–2137PubMedGoogle Scholar
- 18.Wang W, Yang LY, Yang ZL, Huang GW, Lu WQ (2003) Expression and significance of RhoC gene in hepatocellular carcinoma. World J Gastroenterol 9:1950–1953PubMedGoogle Scholar
- 19.Wang W, Yang LY, Huang GW, Lu WQ, Yang ZL, Yang JQ, Liu HL (2004) Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis. Br J Cancer 90:2349–2355PubMedGoogle Scholar
- 20.Yang LY, Wang W, Peng JX, Yang JQ, Huang GW (2004) Differentially expressed genes between solitary large hepatocellular carcinoma and nodular hepatocellular carcinoma. World J Gastroenterol 10:3569–3573PubMedGoogle Scholar
- 21.Charalabopoulos K, Mittari E, Karakosta A, Golias C, Batistatou A (2005) Integrins adhesion molecules and some of their ligands in laryngeal cancer. Exp Oncol 27:86–90PubMedGoogle Scholar
- 22.Gogali A, Charalabopoulos K, Constantopoulos S (2004) Integrin receptors in primary lung cancer. Exp Oncol 26:106–110PubMedGoogle Scholar
- 23.Donald CD, Cooper CR, Harris-Hooker S, Emmett N, Scanlon M, Cooke DB (2001) Cytoskeletal organization and cell motility correlates with metastatic potential and state of differentiation in prostate cancer. Cell Mol Biol (Noisy-le-grand) 47:1033–1038Google Scholar
- 24.Shimizu K, Tani M, Watanabe H, Nagamachi Y, Niinaka Y, Shiroishi T, Ohwada S, Raz A, Yokota J (1999) The autocrine motility factor receptor gene encodes a novel type of seven transmembrane protein. FEBS Lett 456:295–300PubMedCrossRefGoogle Scholar
- 25.Baumann M, Kappl A, Lang T, Brand K, Siegfried W, Paterok E (1990) The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer. Cancer Invest 8:351–356PubMedGoogle Scholar
- 26.Ridley AJ (2001) RhoGTPases and cell migration. J Cell Sci 114:2713–2722PubMedGoogle Scholar
- 27.Clark EA, Golub TR, Lander ES, Hynes RO (2000) Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406:532–535PubMedCrossRefGoogle Scholar