XAF1 mRNA expression improves progression-free and overall survival for patients with advanced bladder cancer treated with neoadjuvant chemotherapy.
OBJECTIVE
The aim of this study was to investigate whether mRNA expression of the apoptosis-associated genes, XAF1 and XIAP, in bladder cancer patients correlates with response to neoadjuvant treatment.


METHODS
Gene expression was analyzed by a real-time quantitative PCR method in paired samples from 14 bladder cancer patients treated with a combination of neoadjuvant gemcitabine and cisplatin. The prognostic significance of XAF1 and XIAP mRNA expression as well as the correlation with several clinical and pathological findings were evaluated.


RESULTS
The clinical response in the XAF1-high subset (n = 5) was remarkably higher compared with the XAF1-low subset (n = 9) (100% vs. 44.4%; P = 0.038). These results translated into a notably improvement of progression-free survival (PFS) in the XAF1-high subset (log-rank P = 0.012). In addition, patients in the XAF1-high subset had a 3.9-fold decreased chance of dying from the disease (hazard ratio for death (HR), 0.257; (CI 95%), 0.043-1.536, P = 0.036). When we evaluated the expression of XIAP, although an inverse correlation was found between expression and pathological response, there were no statistically significant associations with the clinical response, the length of PFS, and OS.


CONCLUSIONS
This is one of the few studies to address the role of XAF1 in a clinical setting. The data presented here identify XAF1 as a novel predictive and prognostic factor in bladder cancer patients. Furthermore, our observations are in line with previous studies, which point towards XAF1 as a tumor-suppressor gene. Nonetheless, additional studies, both mechanistic and translational, are warranted and may help not only in corroborating the role of XAF1 as a prognostic marker, but also as a potential target for anticancer therapy.
Division of Clinical and Translational Research, Research Coordination, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Marcos B
MB
Pinho
Fernanda
F
Costas
João
J
Sellos
Rodrigo
R
Dienstmann
Patricia B
PB
Andrade
Daniel
D
Herchenhorn
Fábio Afonso
FA
Peixoto
Valdelice O
VO
Santos
Isabele A
IA
Small
Denise P
DP
Guimarães
Carlos G
CG
Ferreira
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002945:Cisplatin / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology*; D011379:Prognosis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D000093542:Gemcitabine
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C417551:XAF1 protein, human; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine