title: Nuclear karyopherin-α2 expression in primary lesions and metastatic lymph nodes was associated with poor prognosis and progression in gastric cancer.
abstract: Karyopherin-α2 (KPNA2) functions as an adaptor that transports several proteins to the nucleus. We investigated the clinical and functional significance of KPNA2 in gastric cancer (GC). Immunohistochemistry was performed to examine KPNA2 expression in primary GC and metastatic lymph nodes. Next, KPNA2 was suppressed by small interfering RNA (siRNA) to examine KPNA2 function in proliferation and cisplatin-induced apoptosis of GC cell lines. Nuclear expression of KPNA2 in marginal regions of primary GC was stronger than in central regions of GC and normal tissues. The high expression of marginal KPNA2 was significantly associated with β-catenin accumulation in the nucleus and poor prognosis in two independent GC cohorts (discovery cohort, n = 90, P = 0.018; validation cohort, n = 89, P = 0.0125). We detected correlations between nuclear KPNA2 expression in marginal region and progression of macroscopic type (P = 0.036), tumor depth (P = 0.013), lymph node metastasis (P = 0.0064), venous invasion (P = 0.034) and clinical stage (P = 0.0006). Nuclear KPNA2 expression in marginal regions of metastatic lymph nodes was significantly higher than in the central region. It was associated with poor survival of GC patients with lymph node metastasis (n = 96; center, P = 0.4384; marginal, P < 0.0001). KPNA2 suppression enhanced cisplatin-induced apoptosis and reduced proliferation in the KPNA2 siRNA group compared with the control siRNA group. The expression of the DNA repair gene NBS1 (NBN) in the nucleus was suppressed in KPNA2-suppressed cells. KPNA2 might be a useful prognostic marker and an effective therapeutic target for GC.
authors.affiliation: Department of General Surgical Science and.
authors.forename: Bolag
authors.initials: B
authors.lastname: Altan
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.forename: Erito
authors.initials: E
authors.lastname: Mochiki
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ohno
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ogata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Baigalimaa
authors.initials: B
authors.lastname: Luvsandagva
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D028901:alpha Karyopherins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D028901:alpha Karyopherins; D051176:beta Catenin; C087978:karyopherin alpha 2; D002945:Cisplatin