Skip to main content

Advertisement

SpringerLink
Log in

High RIN1 expression is associated with poor prognosis in patients with gastric adenocarcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

The aim of this study was to investigate the expression and prognostic significance of RIN1 in gastric adenocarcinoma. RIN1 expression was analyzed using quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemical staining on tissue samples from a consecutive series of 315 gastric adenocarcinoma patients who underwent tumor resections between 2003 and 2006. The relationship between RIN1 expression, clinicopathological factors, and patient survival was investigated. qRT-PCR results showed that the RIN1 mRNA expression was higher in tumor tissue samples than in the adjacent normal tissues, and a corresponding increase in protein expression was confirmed by Western blotting. Immunohistochemical staining indicated that RIN1 is highly expressed in 54.3 % of gastric adenocarcinomas. RIN1 expression levels were closely associated with tumor size, histological differentiation, tumor stage, and lymph node involvement. Kaplan–Meier survival analysis showed that high RIN1 expression exhibited a significant correlation with poor prognosis for gastric adenocarcinoma patients. Multivariate analysis revealed that RIN1 expression is an independent prognostic parameter for the overall survival rate of gastric adenocarcinoma patients. Our data suggest that RIN1 plays an important role in gastric adenocarcinoma progression and that a high RIN1 expression predicts an unfavorable prognosis in gastric adenocarcinoma patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Hohenberger P, Gretschel S. Gastric cancer. Lancet. 2003;362:305–15. doi:10.1016/S0140-6736(03)13975-X.

    Article  PubMed  Google Scholar 

  2. Dcken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 2005;241:27–39. doi:10.1097/01.sla.0000149300.28588.23.

    PubMed  PubMed Central  Google Scholar 

  3. Zhang B, Cao W, Zhang F, Zhang L, Niu R, Niu Y, Fu L, Hao X, Cao X. Protein interacting with C alpha kinase 1 (PICK1) is involved in promoting tumor growth and correlates with poor prognosis of human breast cancer. Cancer Sci. 2010;101:1536–42. doi:10.1111/j.1349-7006.2010.01566.x.

    Article  CAS  PubMed  Google Scholar 

  4. Han L, Wong D, Dhaka A, Afar D, White M, Xie W, Herschman H, Witte O, Colicelli J. Protein binding and signaling properties of RIN1 suggest a unique effector function. Proc Natl Acad Sci USA. 1997;94:4954–9. PMCID: PMC24612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Tall GG, Barbieri MA, Stahl PD, Horazdovsky BF. Ras-activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1. Dev Cell. 2001;1:73–82.

    Article  CAS  PubMed  Google Scholar 

  6. Barbieri MA, Kong C, Chen PI, Horazdovsky BF, Stahl PD. The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis. J Biol Chem. 2003;278:32027–36. doi:10.1074/jbc.M304324200.

    Article  CAS  PubMed  Google Scholar 

  7. Hu H, Bliss JM, Wang Y, Colicelli J. RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration. Curr Biol. 2005;15:815–23. doi:10.1016/j.cub.2005.03.049.

    Article  CAS  PubMed  Google Scholar 

  8. Deininger K, Eder M, Kramer ER, Zieglgänsberger W, Dodt HU, Dornmair K, Colicelli J, Klein R. The Rab5 guanylate exchange factor Rin1 regulates endocytosis of the EphA4 receptor in mature excitatory neurons. Proc Natl Acad Sci USA. 2008;105:12539–44. doi:10.1073/pnas.0801174105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dhaka A, Costa RM, Hu H, Irvin DK, Patel A, Kornblum HI, Silva AJ, O’Dell TJ, Colicelli J. The RAS effector RIN1 modulates the formation of aversive memories. J Neurosci. 2003;23:748–57.

    CAS  PubMed  Google Scholar 

  10. Goi T, Senda K, Yamaguchi A. Expression of RIN1 gene in gastric and colorectal cancers. Nihon Geka Gakkai Zasshi. 2001;102:783.

    CAS  PubMed  Google Scholar 

  11. Morikawa J, Li H, Kim S, Nishi K, Ueno S, Suh E, Dougherty E, Shmulevich I, Shiku H, Zhang W, Kobayashi T. Identification of signature genes by microarray for acute myeloid leukemia without maturation and acute promyelocytic leukemia with t(15;17) (q22;q12) (PML/RARalpha). Int J Oncol. 2003;23:617–25.

    CAS  PubMed  Google Scholar 

  12. Milstein M, Mooser CK, Hu H, Fejzo M, Slamon D, Goodglick L, Dry S, Colicelli J. RIN1 is a breast tumor suppressor gene. Cancer Res. 2007;67:11510–6. doi:10.1158/0008-5472.CAN-07-1147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Senda K, Goi T, Hirono Y, Katayama K, Yamaguchi A. Analysis of RIN1 gene expression in colorectal cancer. Oncol Rep. 2007;17:1171–5.

    CAS  PubMed  Google Scholar 

  14. Tomshine JC, Severson SR, Wigle DA, Sun Z, Beleford DA, Shridhar V, Horazdovsky BF. Cell proliferation and epidermal growth factor signaling in non-small cell lung adenocarcinoma cell lines are dependent on Rin1. J Biol Chem. 2009;284:26331–9. doi:10.1074/jbc.M109.033514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chetcuti A, Aktas S, Mackie N, Ulger C, Toruner G, Alkan M, Catchpoole D. Expression profiling reveals MSX1 and EphB2 expression correlates with the invasion capacity of Wilms tumors. Pediatr Blood Cancer. 2011;57:950–7. doi:10.1002/pbc.23003.

    Article  PubMed  Google Scholar 

  16. Fujioka M, Goi T, Hirono Y, Katayama K, Yamaguchi A. Cloning of a novel splicing variant of RIN1 and its expression in gastric and colon cancer. Oncol Res. 2009;17:593–9.

    Article  PubMed  Google Scholar 

  17. Brown RS, Wahl RL. Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer. 1993;72:2979–85.

    Article  CAS  PubMed  Google Scholar 

  18. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  19. Kelly K, Crowley J, Bunn Jr PA, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001;19:3210–8.

    CAS  PubMed  Google Scholar 

  20. Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update. Lancet Oncol. 2004;5:341–53.

    Article  PubMed  Google Scholar 

  21. Shuster MI, Han L, Le Beau MM, Davis E, Sawicki M, Lese CM, Park NH, Colicelli J, Gollin SM. A consistent pattern of RIN1 rearrangements in oral squamous cell carcinoma cell lines supports a breakage–fusion–bridge cycle model for 11q13 amplification. Genes Chromosomes Cancer. 2000;28:153–63.

    Article  CAS  PubMed  Google Scholar 

  22. Zainabadi K, Benyamini P, Chakrabarti R, Veena MS, Chandrasekharappa SC, Gatti RA, Srivatsan ES. A 700-kb physical and transcription map of the cervical cancer tumor suppressor gene locus on chromosome 11q13. Genomics. 2005;85:704–14.

    Article  CAS  PubMed  Google Scholar 

  23. Hu H, Milstein M, Bliss JM, Thai M, Malhotra G, Huynh LC, Colicelli J. Integration of transforming growth factor beta and RAS signaling silences a RAB5 guanine nucleotide exchange factor and enhances growth factor-directed cell migration. Mol Cell Biol. 2008;28:1573–83. doi:10.1128/MCB.01087-07.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of General Surgery, Yixing People’s Hospital, No. 75, Tongzhen Guan Rd, Yixing, China

    Hai-Feng Yu, Jie Chen, Yun Zhang, Tian-Zhou Zha, Kai Zhang, Miao Zhang, Su-Jun Zhou & Chao Jiang

  2. Department of Gastroenterology, Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, 710004, China

    Gang Zhao

  3. Department of Anesthesiology, Yixing People’s Hospital, No. 75, Tongzhen Guan Rd, Yixing, China

    Zhi-Jun Ge

  4. Department of General Surgery, Northern Jiangsu People’s Hospital, No. 95, Nantong Western Rd, Yangzhou, 22500, China

    Hai-Feng Yu, Dao-Rong Wang & Jie Chen

  5. Department of Cardiothoracic Surgery, Yixing People’s Hospital, No. 75, Tongzhen Guan Rd, Yixing, China

    Yong-Fei Tan

Authors
  1. Hai-Feng Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhi-Jun Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dao-Rong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jie Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tian-Zhou Zha
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kai Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Miao Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yong-Fei Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Su-Jun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Chao Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dao-Rong Wang, Su-Jun Zhou or Chao Jiang.

Additional information

Hai-Feng Yu, Gang Zhao, and Zhi-Jun Ge contributed equally to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, HF., Zhao, G., Ge, ZJ. et al. High RIN1 expression is associated with poor prognosis in patients with gastric adenocarcinoma. Tumor Biol. 33, 1557–1563 (2012). https://doi.org/10.1007/s13277-012-0409-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-012-0409-0

Keywords

Search

Navigation