title: ANCCA protein expression is a novel independent poor prognostic marker in surgically resected lung adenocarcinoma.
abstract: BACKGROUND
  AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored.
  
  
  METHODS
  ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions.
  
  
  RESULTS
  Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075-2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955-20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11.
  
  
  CONCLUSIONS
  We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Fang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Pan
authors.forename: Haichuan
authors.initials: H
authors.lastname: Hu
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Luo
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Haiquan
authors.initials: H
authors.lastname: Chen
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ji
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
chemical_list: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C117307:KRAS protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C544857:ATAD2 protein, human