title: Overexpression of T-LAK cell-originated protein kinase predicts poor prognosis in patients with stage I lung adenocarcinoma.
abstract: Tumor recurrence is the most common cause of disease failure after surgical resection in early-stage lung adenocarcinoma. Identification of clinically relevant prognostic markers could help to predict patients with high risk of disease recurrence. A meta-analysis of available lung adenocarcinoma microarray datasets revealed that T-LAK cell-originated protein kinase (TOPK), a serine/threonine protein kinase, is overexpressed in lung cancer. Using stable cell lines with overexpression or knockdown of TOPK, we have shown that TOPK can promote cell migration, invasion, and clonogenic activity in lung cancer cells, suggesting its crucial role in lung tumorigenesis. To evaluate the prognostic value of TOPK expression in resected stage I lung adenocarcinoma, a retrospective analysis of 203 patients diagnosed with pathological stage I lung adenocarcinoma was carried out to examine the expression of TOPK by immunohistochemistry (IHC). The prognostic significance of TOPK overexpression was examined. Overexpression of TOPK (IHC score >3) was detected in 67.0% of patients, and these patients were more frequently characterized with disease recurrence and angiolymphatic invasion. Using multivariate analysis, patient age (>65 years old; P = 0.002) and TOPK overexpression (IHC score >3; P < 0.001) significantly predicted a shortened overall survival. Moreover, TOPK overexpression (IHC score >3; P = 0.005) also significantly predicted a reduced time to recurrence in the patients. Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence.
authors.affiliation: Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Di-Cing
authors.initials: DC
authors.lastname: Wei
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Yeh
authors.forename: Jung-Jyh
authors.initials: JJ
authors.lastname: Hung
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Wu
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Cheng
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Hsu
authors.forename: Yu-Lun
authors.initials: YL
authors.lastname: Kuo
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Lai
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012008:Recurrence; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D017346:Protein Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase