title: Karyopherin alpha 2 is a novel prognostic marker and a potential therapeutic target for colon cancer.
abstract: BACKGROUND
  Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, plays a vital role in carcinogenesis. Yet its role in colon cancer is poorly characterized. We sought to clarify the clinical significance of its dysregulated expression in human colon tumor specimens.
  
  
  METHODS
  We evaluated KPNA2 mRNA and protein expression by real-time polymerase chain reaction and Western blotting in 40 primary colon cancer tissues and paired adjacent normal colon mucosa specimens. KPNA2 protein expression in colon tissue microarray of tumor and normal tissue specimens and lymph node metastasis specimens obtained from 195 colon cancer patients were analyzed immunohistochemically. The effect of KPNA2 knockdown on carcinogenesis potential of human colon cancer cells was determined using Cell Counting Kit-8 (CCK8), colony formation, cell migration, and tumorigenesis in nude mice.
  
  
  RESULTS
  KPNA2 was expressed at higher levels in colon tumors and lymph node metastasis specimens than in normal tissues. Patients with KPNA2-positive tumors were significantly correlated with the American Joint Committee on Cancer (AJCC) stage (p = 0.01), T-classification (p = 0.018), regional lymph node metastasis (p = 0.025), distant metastasis (p = 0.014), and differentiated degree (p = 0.001). KPNA2 was shown to be an independent prognostic indicator of disease-free survival (HR 1.681; 95 % CI: 1.170-2.416; p = 0.005) and overall survival (HR 2.770; 95 % CI: 1.314-5.837; p = 0.007) for patients with colon cancer. Knockdown of KPNA2 expression inhibited colon cancer cell proliferation, colony formation, and migration.
  
  
  CONCLUSIONS
  KPNA2 might play an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for colorectal cancer.
authors.affiliation: Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. zhangyugood217@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. doc_zm@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. fdyush@163.com.
authors.forename: Fudong
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. xuxulusu@163.com.
authors.forename: Su
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. sunhuimin0408@163.com.
authors.forename: Huimin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. huamei-tang@hotmail.com.|Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. huamei-tang@hotmail.com.
authors.forename: Huamei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. pengzhihai1958@163.com.|Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai, 200080, People's Republic of China. pengzhihai1958@163.com.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden; D055815:Young Adult; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D028901:alpha Karyopherins; C087978:karyopherin alpha 2