title: Activated Pak4 expression correlates with poor prognosis in human gastric cancer patients.
abstract: Despite considerable advances in gastrectomy and chemotherapy, the prognosis of gastric cancer (GC) has not noticeably improved due to lymph node or distant metastases. P21-activated serine/threonine kinase 4 (Pak4) plays an important role in cell morphology and cytoskeletal reorganization-both prerequisite steps for cell migration. However, it is still unclear if activated Pak4 (p-Pak4) is related to prognosis in GC patients. In our study, the level of p-Pak4 in 95 GC tissue specimens was examined by immunohistochemistry (IHC). We observed significant correlation between the level of p-Pak4 and grosstype (advanced stage GC vs. early stage GC, P = 0.04). Moreover, GC patients with higher p-Pak4 levels had a poorer prognosis than those with lower p-Pak4 levels (17 vs. 38 months, P = 0.001). Multivariate analysis showed that high phosphorylation level of Pak4, advanced stage GC, and lymph node metastasis were independent prognostic factors for GC patients (p-Pak4, P = 0.026; advanced stage GC, P = 0.030; lymph node metastasis, P = 0.016). In addition, in vitro assays indicated that knockdown of Pak4 accompanied with decreased p-Pak4, inhibited cell migration via downregulation of the traditional downstream signaling pathways of Pak4, LIMK1, and cofilin. In conclusion, this report reveals that high level of p-Pak4 correlates with poor prognosis in GC, thereby suggesting that p-Pak4 might be a potential prognostic marker for GC.
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, China.
authors.forename: Danni
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, China. zhangye@mail.emu.edu.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Respiratory and Infectious disease of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Ximing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Medical Oncology, The First Hospital of China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang, 110001, China. ypliu@mail.cmu.edu.cn.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D054462:p21-Activated Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C116367:PAK4 protein, human; D054462:p21-Activated Kinases
keywords: Gastric cancer; Migration; Prognosis; p-Pak4