Medical Oncology

, 30:726 | Cite as

CRM1 is a novel independent prognostic factor for the poor prognosis of gastric carcinomas

  • Fang Zhou
  • Wensheng Qiu
  • Ruyong Yao
  • Jinyu Xiang
  • Xiaoxiao Sun
  • Shihai Liu
  • Jing Lv
  • Lu YueEmail author
Original Paper


Gastric cancer (GC) is a highly aggressive malignant tumor. Its high mortality rate prompts the urgent need for novel therapeutic agents. The aim of this study is to detect the expression of CRM1 in GC, which has not been reported to date. The expression of CRM1 in GC and adjacent noncancerous tissues (ANCT) of gastrectomy specimens from 120 GC patients was measured by immunohistochemistry. In addition, correlations between the CRM1 staining and the clinicopathologic features as well as survival were analyzed. Positive expression rates of CRM1 in GC and ANCT were 57.8 and 6.7 %, respectively. High expression of CRM1 was significantly associated with increased serum level of carcinoma embryonic antigen (CEA, P = 0.02) but not associated with that of carbohydrate antigen 19–9 (P = 0.38). CRM1 levels were correlated with more advanced tumor stages (P = 0.01), positive Her2 status (P = 0.01), and distant metastasis (P = 0.02). Univariate analysis showed that CEA (P = 0.0076), TNM stage (P = 0.0001), metastasis (P = 0.027), and CRM1 expression (P = 0.0019) were significant risk factors affecting overall survival of GC patients. The multivariate analysis indicated that the CRM1 was an independent indicator for GC survival (P = 0.0048). The current results indicated that CRM1 expressed in a subpopulation of GC with aggressive behavior and could serve as a prognosis marker for poor outcome.


Gastric cancer CRM1 Biomarker Prognosis 



This study is supported by Shandong Natural Science Foundation (2009HW024), Shandong Excellent Young Scientist Research Award Fund Project (2006BSB14114), and Shandong Tackle Key Problems in Science and Technology (2010GSF10245).

Conflict of interest

We have no conflicts of interest to report.


  1. 1.
    Lee J, Lee SH, Hur KY, Woo SY, Kim SW, Kang WK. Statins and the risk of gastric cancer in diabetes patients. BMC Cancer. 2012;12:596.CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Syrios J, Sougioultzis S, Xynos ID, Kavantzas N, Kosmas C, Agrogiannis G, Griniatsos J, Karavokyros I, Pikoulis E, Patsouris ES, et al. Survival in patients with stage IV noncardia gastric cancer—the influence of DNA ploidy and Helicobacter pylori infection. BMC Cancer. 2012;12:264.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Kwon KJ, Shim KN, Song EM, Choi JY, Kim SE, Jung HK, Jung SA. Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the stomach. Gastric Cancer. 2013 [Epub ahead of print].Google Scholar
  4. 4.
    Liu D, Zhang L, Shen Z, Tan F, Hu Y, Yu J, Li G. Clinicopathological significance of NMIIA Overexpression in Human Gastric Cancer. Int J Mol Sci. 2012;13:15291–304.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Wang JH, Mai C, Hong J, Zhang Q, Tang HS, Tang YQ, Cui SZ. Predicting value of serum CEA and CA19-9 in neoadjuvant chemotherapy for advanced gastric carcinoma. Zhonghua Wei Chang Wai Ke Za Zhi. 2012;15:1273–6.PubMedGoogle Scholar
  6. 6.
    Camara Mde L, Bouvier LA, Canepa GE, Miranda MR, Pereira CA. Molecular and functional characterization of a Trypanosoma cruzi nuclear adenylate kinase isoform. PLoS Negl Trop Dis. 2013;7:e2044.CrossRefPubMedGoogle Scholar
  7. 7.
    Zhang KJ, Wang M. Potential effects of CRM1 inhibition in mantle cell lymphoma. Chin J Cancer Res. 2012;24:374–87.CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Shen A, Wang Y, Zhao Y, Zou L, Sun L, Cheng C. Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis. Neurosurgery. 2009;65:153–9 (discussion 159–160).CrossRefPubMedGoogle Scholar
  9. 9.
    Yao Y, Dong Y, Lin F, Zhao H, Shen Z, Chen P, Sun YJ, Tang LN, Zheng SE. The expression of CRM1 is associated with prognosis in human osteosarcoma. Oncol Rep. 2009;21:229–35.PubMedGoogle Scholar
  10. 10.
    Huang WY, Yue L, Qiu WS, Wang LW, Zhou XH, Sun YJ. Prognostic value of CRM1 in pancreas cancer. Clin Invest Med. 2009;32:E315.PubMedGoogle Scholar
  11. 11.
    Noske A, Weichert W, Niesporek S, Roske A, Buckendahl AC, Koch I, Sehouli J, Dietel M, Denkert C. Expression of the nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 is a prognostic factor in human ovarian cancer. Cancer. 2008;112:1733–43.CrossRefPubMedGoogle Scholar
  12. 12.
    van der Watt PJ, Maske CP, Hendricks DT, Parker MI, Denny L, Govender D, Birrer MJ, Leaner VD. The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation. Int J Cancer. 2009;124:1829–40.CrossRefPubMedGoogle Scholar
  13. 13.
    Jiang CG, Xu Y, Wang ZN, Sun Z, Liu FN, Yu M, Xu HM. Clinicopathological analysis and prognostic significance of peritoneal cytology in Chinese patients with advanced gastric cancer. ANZ J Surg. 2011;81:608–13.CrossRefPubMedGoogle Scholar
  14. 14.
    Nesi G, Basili G, Girardi LR, Manetti A, Biliotti G, Barchielli A. Pathological predictors of lymph node involvement in submucosal gastric carcinoma: a retrospective analysis of long-term outcome. In Vivo. 2009;23:337–41.PubMedGoogle Scholar
  15. 15.
    Jiexian J, Xiaoqin X, Lili D, Baoguo T, Ting S, Xianwen Z, Cunzhi H. Clinical assessment and prognostic evaluation of tumor markers in patients with gastric cancer. Int J Biol Mark. 2013;28:e192–200.CrossRefGoogle Scholar
  16. 16.
    Zhang X, Hakata Y, Tanaka Y, Shida H. CRM1, an RNA transporter, is a major species-specific restriction factor of human T cell leukemia virus type 1 (HTLV-1) in rat cells. Microbes Infect. 2006;8:851–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Smulevitch S, Michalowski D, Zolotukhin AS, Schneider R, Bear J, Roth P, Pavlakis GN, Felber BK. Structural and functional analysis of the RNA transport element, a member of an extensive family present in the mouse genome. J Virol. 2005;79:2356–65.CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Li J, Shiraki T, Igarashi K. Bach1 as a regulator of mitosis, beyond its transcriptional function. Commun Integr Biol. 2012;5:477–9.CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    He W, Wang X, Chen L, Guan X. A crosstalk imbalance between p27(Kip1) and its interacting molecules enhances breast carcinogenesis. Cancer Biother Radiopharm. 2012;27:399–402.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Fukumoto M, Sekimoto T, Yoneda Y. Proteomic analysis of importin alpha-interacting proteins in adult mouse brain. Cell Struct Funct. 2011;36:57–67.CrossRefPubMedGoogle Scholar
  21. 21.
    Wang YC, Zhang DM, Shen AG, Lu JX, Shao XY, He S, Cheng C. Expression and relationship of p27(kip1) and its related molecules Jab1 and CRM1 during proliferation of lymphoma cells U937. Zhonghua Zhong Liu Za Zhi. 2007;29:657–61.PubMedGoogle Scholar
  22. 22.
    Budhu AS, Wang XW. Loading and unloading: orchestrating centrosome duplication and spindle assembly by Ran/Crm1. Cell Cycle. 2005;4:1510–4.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Siddiqui N, Borden KL. mRNA export and cancer. Wiley Interdiscip Rev RNA. 2012;3:13–25.CrossRefPubMedGoogle Scholar
  24. 24.
    Dearling JL, Flynn AA, Qureshi U, Whiting S, Boxer GM, Green A, Begent RH, Pedley RB. Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake. Nucl Med Biol. 2009;36:883–94.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Fang Zhou
    • 1
    • 2
  • Wensheng Qiu
    • 1
  • Ruyong Yao
    • 3
  • Jinyu Xiang
    • 1
    • 4
  • Xiaoxiao Sun
    • 1
  • Shihai Liu
    • 3
  • Jing Lv
    • 1
  • Lu Yue
    • 1
    Email author
  1. 1.Department of Oncology, Affiliated Hospital of Medical CollegeQingdao UniversityQingdaoChina
  2. 2.Department of RadiotherapyYantai Yuhuangding Hospital Affiliated to Medical College of Qingdao UniversityYantaiChina
  3. 3.Central Laboratory, Affiliated Hospital of Medical CollegeQingdao UniversityQingdaoChina
  4. 4.Department of OncologyYantai Yuhuangding Hospital Affiliated to Medical College of Qingdao UniversityYantaiChina

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