title: Aberrant expression of nuclear KPNA2 is correlated with early recurrence and poor prognosis in patients with small hepatocellular carcinoma after hepatectomy.
abstract: 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 < 0.05). Nuclear KPNA2 expression was associated with a poor prognosis in HCC patients. Univariate and multivariate analyses demonstrated that KPNA2 was an independent prognostic factor for both overall survival (p < 0.001) and time to recurrence (p < 0.001) in HCC patients. Furthermore, in a validation cohort, nuclear expression of KPNA2 was observed in 16 of 47 (34.0 %) small hepatocellular carcinoma patients. Importantly, the risk of recurrence associated with nuclear KPNA2 expression (9/16, 56.2 %) was significantly higher than the risk associated with an absence of nuclear KPNA2 expression (6/31, 19.3 %; p = 0.01). Our results demonstrate that nuclear KPNA2 expression is a poor prognostic biomarker for HCC, especially for early-stage HCC.
authors.affiliation: Department of Hepatobiliary Oncology, Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou, 510095, Guangdong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Tang
authors.forename: Lu
authors.initials: L
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Cong
authors.initials: C
authors.lastname: Mai
authors.forename: Lijuan
authors.initials: L
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism*; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D011379:Prognosis; D028901:alpha Karyopherins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C490630:KPNA2 protein, human; D028901:alpha Karyopherins