title: Prognostic and predictive role of JWA and XRCC1 expressions in gastric cancer.
abstract: OBJECTIVE
  To investigate the expression pattern and significance of DNA repair genes JWA and X-ray repair cross complement group 1 (XRCC1) in gastric cancer.
  
  
  METHODS
  Expressions of JWA and XRCC1 were assessed by immunohistochemistry in a training cohort and they went into a second testing cohort and finally to a validating cohort. Prognostic and predictive role of JWA and XRCC1 expression status in cases treated with surgery alone or combined with adjuvant chemotherapy was evaluated, respectively.
  
  
  RESULTS
  JWA and XRCC1 protein levels were significantly downregulated in gastric cancer lesions compared with adjacent noncancerous tissues. Low tumoral JWA or XRCC1 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients without adjuvant treatment. Multivariate regression analysis showed that low JWA and XRCC1 expressions, separately and together, were independent negative markers of OS. Adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) significantly improved OS compared with surgery alone (log-rank test, P = 0.01). However, this effect was evident only in the JWA or XRCC1 low expression group (HR = 0.44; 95% CI: 0.26-0.73; P = 0.002, and HR = 0.44, 95% CI: 0.26-0.75; P = 0.002, respectively); Adjuvant fluorouracil-leucovorin-platinol (FLP) did not improve OS, except in the patients with low JWA and XRCC1 expressions (P = 0.010 for JWA and 0.024 for XRCC1, respectively).
  
  
  CONCLUSIONS
  JWA and XRCC1 protein expressions in tumor are novel candidate prognostic markers and predictive factors for benefit from adjuvant platinum-based chemotherapy (FLO or FLP) in resectable human gastric carcinoma.
authors.affiliation: Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center; School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.forename: Xuming
authors.initials: X
authors.lastname: Wu
authors.forename: Yansu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jianbing
authors.initials: J
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ding
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Tan
authors.forename: Fulin
authors.initials: F
authors.lastname: Qiang
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.forename: Jinyan
authors.initials: J
authors.lastname: Zeng
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Gong
authors.forename: Aiping
authors.initials: A
authors.lastname: Li
authors.forename: Gang
authors.initials: G
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; D017024:Chemotherapy, Adjuvant; D002681:China; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D026901:Membrane Transport Proteins; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: C484566:ARL6IP5 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D009944:Organoplatinum Compounds; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil