Prognostic importance and therapeutic implications of PAK1, a drugable protein kinase, in gastroesophageal junction adenocarcinoma.
Gastroesophageal junction (GEJ) adenocarcinoma is a lethal cancer with rising incidence, yet the molecular biomarkers that have strong prognostic impact and also hold great therapeutic promise remain elusive. We used a data mining approach and identified the p21 protein-activated kinase 1 (PAK1), an oncogene and drugable protein kinase, to be among the most promising targets for GEJ adenocarcinoma. Immunoblot analysis and data mining demonstrated that PAK1 protein and mRNA were upregulated in cancer tissues compared to the noncancerous tissues. Immunohistochemistry revealed PAK1 overexpression in 72.6% of primary GEJ adenocarcinomas (n = 113). A step-wise increase in PAK1 levels was noted from paired normal epithelium, to atypical hyperplasia and adenocarcinoma. PAK1 overexpression in tumor was associated with lymph node (LN) metastasis (P<0.001), advanced tumor stage (P<0.001), large tumor size (P = 0.006), residual surgical margin (P = 0.033), and unfavorable overall survival (P<0.001). Multivariate analysis showed PAK1 overexpression is an independent high-risk prognostic predictor (P<0.001). Collectively, PAK1 is overexpressed during tumorigenic progression and its upregulation correlates with malignant properties mainly relevant to invasion and metastasis. PAK1 expression could serve as a prognostic predictor that holds therapeutic promise for GEJ adenocarcinoma.
Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, China ; Cancer Research Center, Shantou University Medical College, Shantou, China.
Zongtai
Z
Li
Xiaofang
X
Zou
Liangxi
L
Xie
Hongmei
H
Dong
Yuping
Y
Chen
Qing
Q
Liu
Xiao
X
Wu
David
D
Zhou
Dongfeng
D
Tan
Hao
H
Zhang
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D019295:Computational Biology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004943:Esophagogastric Junction / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D054462:p21-Activated Kinases