Clinical significance of hepatocyte growth factor/c-Met expression in the assessment of gastric cancer progression

Noguchi,Eiichiro; Saito,Noboru; Kobayashi,Makio; Kameoka,Shingo

doi:10.3892/mmr.2015.3205

Clinical significance of hepatocyte growth factor/c-Met expression in the assessment of gastric cancer progression

Authors:
- Eiichiro Noguchi
- Noboru Saito
- Makio Kobayashi
- Shingo Kameoka
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Affiliations: Department of Surgery II, Tokyo Women's Medical University, Tokyo 162‑8666, Japan, Department of Pathology I, Tokyo Women's Medical University, Tokyo 162‑8666, Japan
Published online on: January 15, 2015 https://doi.org/10.3892/mmr.2015.3205
Pages: 3423-3431
Copyright: © Noguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Among the mechanisms that control cancer progression, cell mobility is a significant factor required for cellular liberation from the primary focus and infiltration. Hepatocyte growth factor (HGF) has been shown to facilitate cell mobility. In the present study, the clinical significance of the HGF/c‑Met pathway in the assessment of gastric cancer progression was evaluated. From a cohort of patients with gastric cancer who underwent surgical resection between April 1999 and March 2003, 110 subjects were randomly selected. Preoperative serum HGF levels were measured and various pathological factors were analyzed. Furthermore, 50 subjects were randomly selected from within this group and immunohistochemical staining of tissue preparations for HGF and its receptor c‑Met were performed. In the infiltrative growth pattern [(INF)α,β vs. INFγ], advanced progression was associated with elevated preoperative serum HGF levels (P<0.001). No correlation was identified between serum HGF levels and immunostaining for HGF or c‑Met in the tissue preparations. Immunostaining revealed a significant correlation between c‑Met expression and lymphatic vessel invasion (ly0.1 vs. 2.3; P=0.0416), lymph node metastasis (n0.1 vs. 2; P=0.0184) and maximum tumor diameter (≤50 mm vs. >50 mm; P=0.0469). Furthermore, c‑Met‑positivity was associated with a significant difference in overall survival (P=0.0342), despite stage I and II cases accounting for 82% of the total cohort (41 of 50 cases). These results suggested that the expression of the HGF/c‑Met pathway in gastric cancer may be a potential predictive factor for disease progression.

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1	Yamada A, Saito N, Kameoka S and Kobayashi M: Clinical significance of epidermal growth factor (EGF) expression in gastric cancer. Hepatogastroenterology. 54:1049–1052. 2007.PubMed/NCBI
2	Hirosawa T, Saito N, Kameoka S and Kobayashi M: Clinical significance of epidermal growth factor (EGF) expression for assessing the spreading of human colon cancer. Nippon Daicho Komonbyo Gakkai Zasshi. 55:402–412. 2002.(In Japanese). View Article : Google Scholar
3	Soyama K, Saito N and Kameoka S: Study on adhesion molecule beta1 integrin in colorectal cancer-quantification of blood levels and immunohistological staining. Nippon Daicho Komonbyo Gakkai Zasshi. 52:119–127. 1999.(In Japanese). View Article : Google Scholar
4	Saito N, Nishimura H and Kameoka S: Clinical significance of fibronectin expression in colorectal cancer. Mol Med Rep. 1:77–81. 2008.PubMed/NCBI
5	Tani H, Saito N, Kobayashi M and Kameoka S: Clinical significance of keratinocyte growth factor and K-sam gene expression in gastric cancer. Mol Med Rep. 7:1381–1386. 2013.PubMed/NCBI
6	Suda A, Saito N, Seshimo A, Kameoka S and Kobayashi M: Examination of transforming growth factor beta1 expression in the serum and tumor tissue of gastric cancer. Int Surg. 94:182–188. 2009.
7	Daiko W, Saito N and Kameoka S: Clinical significance of TGF-beta1 expression in evaluation of the malignancy of colorectal cancer. Nippon Daicho Komonbyo Gakkai Zasshi. 58:377–382. 2005.(In Japanese). View Article : Google Scholar
8	Hashimoto T, Saito N, Kameoka S, Shibata N and Kobayashi M: Clinical significance of hepatocyte growth factor and its specific receptor c-Met expression in colorectal cancer progression. Acta Histochem Cytochem. 37:139–146. 2004. View Article : Google Scholar
9	Nakamura T, Nawa K and Ichihara A: Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun. 122:1450–1459. 1984. View Article : Google Scholar : PubMed/NCBI
10	Nakamura T, Teramoto H and Ichihara A: Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sci USA. 83:6489–6493. 1986. View Article : Google Scholar : PubMed/NCBI
11	Nakamura T, Nawa K, Ichihara A, Kaise N and Nishino T: Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett. 224:311–316. 1987. View Article : Google Scholar : PubMed/NCBI
12	Nakamura T, Nishizawa T, Hagiya M, et al: Molecular cloning and expression of human hepatocyte growth factor. Nature. 342:440–443. 1989. View Article : Google Scholar : PubMed/NCBI
13	Higashio K, Shima N, Goto M, et al: Identity of a tumor cytotoxic factor from human fibroblasts and hepatocyte growth factor. Biochem Biophys Res Commun. 170:397–404. 1990. View Article : Google Scholar : PubMed/NCBI
14	Stoker M and Gherardi E: Regulation of cell movement: the motogenic cytokines. Biochim Biophys Acta. 1072:81–102. 1991.PubMed/NCBI
15	Nakamura T: Structure and function of hepatocyte growth factor. Prog Growth Factor Res. 3:67–85. 1991. View Article : Google Scholar : PubMed/NCBI
16	Botraro DP, Rubin JS, Faletro DL, et al: Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 251:802–804. 1991. View Article : Google Scholar
17	Naldini L, Weidner KM, Vigna E, et al: Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J. 10:2867–2878. 1991.PubMed/NCBI
18	Conrotto P, Valdembri D, Corso S, et al: Sema4D induces angiogenesis through Met recruitment by Plexin B1. Blood. 105:4321–4329. 2005. View Article : Google Scholar : PubMed/NCBI
19	Yi S and Tsao MS: Activation of hepatocyte growth factor-met autocrine loop enhances tumorigenicity in a human lung adenocarcinoma cell line. Neoplasia. 2:226–234. 2000. View Article : Google Scholar : PubMed/NCBI
20	Schmidt L, Duh FM, Chen F, et al: Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet. 16:68–73. 1997. View Article : Google Scholar : PubMed/NCBI
21	Schmidt L, Junker K, Weirich G, et al: Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene. Cancer Res. 58:1719–1722. 1998.PubMed/NCBI
22	Park WS, Dong SM, Kim SY, et al: Somatic mutations in the kinase domain of the Met/hepatocyte growth factor receptor gene in childhood hepatocellular carcinomas. Cancer Res. 59:307–310. 1999.PubMed/NCBI
23	Lee JH, Han SU, Cho H, et al: A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene. 19:4947–4953. 2000. View Article : Google Scholar : PubMed/NCBI
24	Ma PC, Kijima T, Maulik G, et al: c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res. 63:6272–6281. 2003.PubMed/NCBI
25	Ma PC, Jagdeesh S, Jagadeeswaran R, et al: c-MET expression/activation, functions and mutations in non-small cell lung cancer. Proc Am Assoc Cancer Res. 44:18752004.
26	Christensen JG, Burrows J and Salgia R: c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett. 225:1–26. 2005. View Article : Google Scholar : PubMed/NCBI
27	Nakamura T, Sakai K, Nakamura T and Matsumoto K: Hepatocyte growth factor twenty years on: Much more than a growth factor. J Gastroenterol Hepatol. 26:188–202. 2011. View Article : Google Scholar : PubMed/NCBI
28	Japanese Gastric Cancer Association. Gastric cancer. 1. Japanese Classification of Gastric Carcinoma. 2nd English Edition. June. 1998, pp. 10–24
29	Hattori Y, Itoh H, Uchino S, et al: Immunohistochemical detection of K-sam protein in stomach cancer. Clin Cancer Res. 2:1373–1381. 1996.PubMed/NCBI
30	Maeda K, Chung YS, Ogawa Y, et al: Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 77:858–863. 1996. View Article : Google Scholar : PubMed/NCBI
31	Nishimoto N: Identification of clinicopathological and molecular prognostic factors in patients of gastric cancer by multivariate analyses. Hiroshima J Med Sci. 49:171–181. 2001.(In Japanese).
32	Wu CW, Chi CW, Su TL, Liu TY, Lui WY and P’eng FK: Serum hepatocyte growth factor level associate with gastric cancer progression. Anticancer Res. 18:3657–3659. 1998.PubMed/NCBI
33	Han SU, Lee JH, Kim WH, Cho YK and Kim MW: Significant correlation between serum level of hepatocyte growth factor and progression of gastric carcinoma. World J Surg. 23:1176–1180. 1999. View Article : Google Scholar : PubMed/NCBI
34	Taniguchi T, Kitamura M, Arai K, Iwasaki Y, Yamamoto Y, Igari A and Toi M: Increase in the circulating level of hepatocyte growth factor in gastric cancer patients. Br J Cancer. 75:673–677. 1997. View Article : Google Scholar : PubMed/NCBI
35	Niki M, Okajima K, Isozaki H, et al: Clinical evaluation of preoperative measurement of the serum human hepatocyte growth factor levels in patients of gastric cancer. Jpn J Gastroenterol Surg. 28:2139–2144. 1995.(In Japanese). View Article : Google Scholar
36	Ide T, Kitajima Y, Miyoshi A, et al: Tumor-stromal cell interaction under hypoxia increases the invasiveness of pancreatic cancer cells through the hepatocyte growth factor/c-Met pathway. Int J Cancer. 119:2750–2759. 2006. View Article : Google Scholar : PubMed/NCBI
37	Jiang WG, Martin TA, Parr C, Davies G, Matsumoto K and Nakamura T: Hepatocyte growth factor, its receptor, and their potential value in cancer therapies. Crit Rev Oncol Hematol. 53:35–69. 2005. View Article : Google Scholar
38	Catenacci DV, Cervantes G, Yala S, et al: RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma. Cancer Biol Ther. 12:9–46. 2011. View Article : Google Scholar : PubMed/NCBI
39	Li Y, Chen CQ, He YL, Cai SR, Yang DJ, et al: Abnormal expression of e-cadherin in tumor cells is associated with poor prognosis of gastric carcinoma. J Surg Oncol. 106:304–310. 2012. View Article : Google Scholar : PubMed/NCBI
40	Taniguchi K, Yonemura Y, Nojima N, et al: The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor. Cancer. 82:2112–2122. 1998. View Article : Google Scholar : PubMed/NCBI
41	Nakajima M, Sawada H, Yamada Y, et al: The prognostic significance of amplification and overexpression of c-met and c-erb B-2 in human gastric carcinomas. Cancer. 85:1894–1902. 1999. View Article : Google Scholar : PubMed/NCBI
42	Huang TJ, Wang JY, Lin SR, Lian ST and Hsieh JS: Overexpression of the c-met protooncogene in human gastric carcinoma: Correlation to clinical features. Acta Oncol. 40:638–643. 2001. View Article : Google Scholar
43	Kubicka S, Claas C, Staab S, et al: p53 mutation pattern and expression of c-erbB2 and c-met in gastric cancer: relation to histological subtypes, Helicobacter pylori infection, and prognosis. Dig Dis Sci. 47:114–121. 2002. View Article : Google Scholar : PubMed/NCBI
44	Han SU, Lee HY, Lee JH, et al: Modulation of E-cadherin by hepatocyte growth factor induces aggressiveness of gastric carcinoma. Ann Surg. 242:676–683. 2005. View Article : Google Scholar : PubMed/NCBI
45	Drebber U, Baldus SE, Nolden B, et al: The overexpression of c-met as a prognostic indicator for gastric carcinoma compared to p53 and p21 nuclear accumulation. Oncol Rep. 19:1477–1483. 2008.PubMed/NCBI
46	Zhao J, Zhang X and Xin Y: Up-regulated expression of Ezrin and c-Met proteins are related to the metastasis and prognosis of gastric carcinomas. Histol Histopathol. 26:1111–1120. 2011.PubMed/NCBI
47	Iveson T, Donehower RC, Davidenko I, et al: Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 15:1007–1018. 2014. View Article : Google Scholar : PubMed/NCBI
48	Davidenko I, Iveson T, Donehower RC, et al: Updated efficacy, biomarker, and exposure-response data form a phase 2 study of rilotumumab (R) plus epirubicin, cisplatin, and capecitabine (ECX) in gastric (G) or esophagogastric junction (EGJ) cancer. In: European Society for Medical Oncology Congress; Vienna. pp. 687P2012
49	Yamada Yasuhide: Molecular therapy for gastric cancer. Chin Clin Oncol. 2:52013.