Aberrant expression of nuclear KPNA2 is correlated with early recurrence and poor prognosis in patients with small hepatocellular carcinoma after hepatectomy

详细信息    查看全文

• 作者：Peng Jiang (1)
  Yunqiang Tang (1)
  Lu He (1)
  Hui Tang (1)
  Min Liang (1)
  Cong Mai (1)
  Lijuan Hu (2)
  Jian Hong (1)
  
• 关键词：Small hepatocellular carcinoma (sHCC) ; Hepatectomy ; KPNA2 ; Early recurrence
• 刊名：Medical Oncology
• 出版年：2014
• 出版时间：August 2014
• 年：2014
• 卷：31
• 期：8
• 全文大小：4,311 KB
• 参考文献：1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-0. doi:10.3322/caac.20107 . CrossRef
  2. Hong J, Hu K, Yuan Y, Sang Y, Bu Q, Chen G, et al. CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma. J Clin Investig. 2012;122(6):2165-5. doi:10.1172/jci61380 . CrossRef
  3. Suh SW, Lee KW, Lee JM, You T, Choi Y, Kim H, et al. Prediction of aggressiveness in early-stage hepatocellular carcinoma for selection of surgical resection. J Hepatol. 2014;. doi:10.1016/j.jhep.2014.01.027 .
  4. Kelley JB, Talley AM, Spencer A, Gioeli D, Paschal BM. Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors. BMC Cell Biol. 2010;11:63. doi:10.1186/1471-2121-11-63 . CrossRef
  5. Radu A, Blobel G, Moore MS. Identification of a protein complex that is required for nuclear protein import and mediates docking of import substrate to distinct nucleoporins. Proc Natl Acad Sci USA. 1995;92(5):1769-3. CrossRef
  6. Weis K, Mattaj IW, Lamond AI. Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences. Science (New York, NY). 1995;268(5213):1049-3. CrossRef
  7. Weis K, Ryder U, Lamond AI. The conserved amino-terminal domain of hSRP1 alpha is essential for nuclear protein import. EMBO J. 1996;15(8):1818-5.
  8. Hogarth CA, Calanni S, Jans DA, Loveland KL. Importin alpha mRNAs have distinct expression profiles during spermatogenesis. Dev Dyn. 2006;235(1):253-2. doi:10.1002/dvdy.20569 . CrossRef
  9. Hall MN, Griffin CA, Simionescu A, Corbett AH, Pavlath GK. Distinct roles for classical nuclear import receptors in the growth of multinucleated muscle cells. Dev Biol. 2011;357(1):248-8. doi:10.1016/j.ydbio.2011.06.032 . CrossRef
  10. Cabot RA, Prather RS. Cleavage stage porcine embryos may have differing developmental requirements for karyopherins alpha2 and alpha3. Mol Reprod Dev. 2003;64(3):292-01. doi:10.1002/mrd.10238 . CrossRef
  11. Fischer N, Kremmer E, Lautscham G, Mueller-Lantzsch N, Grasser FA. Epstein-Barr virus nuclear antigen 1 forms a complex with the nuclear transporter karyopherin alpha2. J Biol Chem. 1997;272(7):3999-005. CrossRef
  12. Qu Q, Sawa H, Suzuki T, Semba S, Henmi C, Okada Y, et al. Nuclear entry mechanism of the human polyomavirus JC virus-like particle: role of importins and the nuclear pore complex. J Biol Chem. 2004;279(26):27735-2. doi:10.1074/jbc.M310827200 . CrossRef
  13. Merle E, Rose RC, LeRoux L, Moroianu J. Nuclear import of HPV11 L1 capsid protein is mediated by karyopherin alpha2beta1 heterodimers. J Cell Biochem. 1999;74(4):628-7. CrossRef
  14. Noetzel E, Rose M, Bornemann J, Gajewski M, Knuchel R, Dahl E. Nuclear transport receptor karyopherin-alpha2 promotes malignant breast cancer phenotypes in vitro. Oncogene. 2012;31(16):2101-4. doi:10.1038/onc.2011.403 . CrossRef
  15. Altan B, Yokobori T, Mochiki E, Ohno T, Ogata K, Ogawa A, et al. Nuclear karyopherin-alpha2 expression in primary lesions and metastatic lymph nodes was associated with poor prognosis and progression in gastric cancer. Carcinogenesis. 2013;34(10):2314-1. doi:10.1093/carcin/bgt214 . CrossRef
  16. Wang CI, Chien KY, Wang CL, Liu HP, Cheng CC, Chang YS, et al. Quantitative proteomics reveals regulation of karyopherin subunit alpha-2 (KPNA2) and its potential novel cargo proteins in nonsmall cell lung cancer. Mol Cell Proteomics. 2012;11(11):1105-2. doi:10.1074/mcp.M111.016592 . CrossRef
  17. Zheng M, Tang L, Huang L, Ding H, Liao WT, Zeng MS, et al. Overexpression of karyopherin-2 in epithelial ovarian cancer and correlation with poor prognosis. Obstet Gynecol. 2010;116(4):884-1. doi:10.1097/AOG.0b013e3181f104ce . CrossRef
  18. Jensen JB, Munksgaard PP, Sorensen CM, Fristrup N, Birkenkamp-Demtroder K, Ulhoi BP, et al. High expression of karyopherin-alpha2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy. Eur Urol. 2011;59(5):841-. doi:10.1016/j.eururo.2011.01.048 . CrossRef
  19. He L, Zhou X, Qu C, Tang Y, Zhang Q, Hong J. Serglycin (SRGN) overexpression predicts poor prognosis in hepatocellular carcinoma patients. Med Oncol (Northwood, London, England). 2013;30(4):707. doi:10.1007/s12032-013-0707-4 . CrossRef
  20. He L, Zhou X, Qu C, Hu L, Tang Y, Zhang Q, et al. Musashi2 predicts poor prognosis and invasion in hepatocellular carcinoma by driving epithelial-mesenchymal transition. J Cell Mol Med. 2014;18(1):49-8. doi:10.1111/jcmm.12158 . CrossRef
  21. Sherman M. Recurrence of hepatocellular carcinoma. N Engl J Med. 2008;359(19):2045-. doi:10.1056/NEJMe0807581 . CrossRef
  22. Poon RT. Differentiating early and late recurrences after resection of HCC in cirrhotic patients: implications on surveillance, prevention, and treatment strategies. Ann Surg Oncol. 2009;16(4):792-. doi:10.1245/s10434-009-0330-y . CrossRef
  23. Hong J, Yuan Y, Wang J, Liao Y, Zou R, Zhu C, et al. Expression of variant isoforms of the tyrosine kinase SYK determines the prognosis of hepatocellular carcinoma. Cancer Res. 2014;74(6):1845-6. doi:10.1158/0008-5472.can-13-2104 . CrossRef
  24. Radu A, Moore MS, Blobel G. The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex. Cell. 1995;81(2):215-2. CrossRef
  25. Dankof A, Fritzsche FR, Dahl E, Pahl S, Wild P, Dietel M, et al. KPNA2 protein expression in invasive breast carcinoma and matched peritumoral ductal carcinoma in situ. Virchows Arch. 2007;451(5):877-1. doi:10.1007/s00428-007-0513-5 . CrossRef
  
• 作者单位：Peng Jiang (1)
  Yunqiang Tang (1)
  Lu He (1)
  Hui Tang (1)
  Min Liang (1)
  Cong Mai (1)
  Lijuan Hu (2)
  Jian Hong (1)
  
  1. Department of Hepatobiliary Oncology, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
  2. Department of Medical Oncology, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, 510095, Guangdong, China
  
• ISSN：1559-131X

文摘

Karyopherin α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. Emerging evidence suggests that KPNA2 plays a crucial role in oncogenesis and early recurrence. In the present study, we evaluated the expression pattern of KPNA2 in 221 hepatocellular carcinoma (HCC) specimens and matching adjacent, non-tumorous tissues (NT) by immunohistochemical assays. We found that nuclear KPNA2 expression was significantly upregulated (30.3?%, 67/221) in HCC tissues; however, no nuclear expression of KPNA2 in NT tissues was observed. A correlation analysis demonstrated that nuclear KPNA2 expression was positively associated with serum AFP level, tumor differentiation, vascular invasion, BCLC stage and early recurrence (all p?p?p?p?=?0.01). Our results demonstrate that nuclear KPNA2 expression is a poor prognostic biomarker for HCC, especially for early-stage HCC.