title: High FAK combined with low JWA expression: clinical prognostic and predictive role for adjuvant fluorouracil-leucovorin-oxaliplatin treatment in resectable gastric cancer patients.
abstract: BACKGROUND
  The multifunctional protein JWA was previously identified as a novel regulator of focal adhesion kinase (FAK/PTK2) in suppressing cancer cell adhesion, invasion and metastasis. JWA is downregulated in gastric cancer (GC) and a prognostic and predictive biomarker for resectable GC. However, the value of FAK combined with JWA for GC patients as a biomarker has not been studied. Here we evaluated the roles of FAK alone and combined with JWA in GC patients treated with surgery alone or combined with adjuvant platinum-based chemotherapy.
  
  
  METHODS
  Two tissue microarrays were constructed of specimens from resected GC (n = 709 in total) for detection of FAK and JWA expression by immunohistochemistry. Correlations between both proteins and clinicopathological features as well as prognostic and predictive values were evaluated.
  
  
  RESULTS
  Compared with adjacent non-cancerous tissues, FAK protein levels were remarkably up-regulated in GC lesions (P < 0.001). High FAK alone or combined with low JWA expression significantly correlated with worse overall survival (OS) (both P < 0.001 in two cohorts). Simultaneously, JWA plus FAK expression was a more valuable prognostic biomarker than JWA or FAK alone. Moreover, the patients with high FAK only or combined with low JWA had significant benefit from adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) therapy compared with those with surgery alone (P = 0.003); however, the cases with adjuvant fluorouracil-leucovorin-cisplatin (FLP) therapy did not show these effects.
  
  
  CONCLUSIONS
  FAK plus JWA may serve as a more prognostic and predictive biomarker for GC than each separately with a potential clinical application.
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People's Republic of China.
authors.forename: Yansu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xia
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.forename: Xuming
authors.initials: X
authors.lastname: Wu
authors.forename: Jianbing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Tan
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.forename: Fulin
authors.initials: F
authors.lastname: Qiang
authors.forename: Aiping
authors.initials: A
authors.lastname: Li
authors.forename: Oluf Dimitri
authors.initials: OD
authors.lastname: Røe
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D005743:Gastrectomy; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery
chemical_list: C484566:ARL6IP5 protein, human; D014408:Biomarkers, Tumor; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D051418:Focal Adhesion Kinase 2; D002955:Leucovorin; D005472:Fluorouracil