Association of steroid and xenobiotic receptor (SXR) and multidrug resistance 1 (MDR1) gene expression with survival among patients with invasive bladder carcinoma.
What's known on the subject? and What does the study add? SXR and MDR1 are known as responsible for chemo and radiotherapy resistance in some cancers, like kidney cancer (MDR1). Invasive bladder cancer is an aggressive disease, with different behaviour upon its tumoral stage, and also within the same tumoral stage, therefore molecular markers are sought. This study shows a new molecular marker, which has shown as a predictor for bad prognosis cancers, therefore, allowing us for a better patient selection for aggressive therapies.


OBJECTIVE
To investigate the prognostic value of steroid and xenobiotic receptor (SXR) and multidrug resistance 1 (MDR1) gene expression in relation to survival among patients with invasive bladder cancer.


METHODS
The prospective study included 67 patients diagnosed with invasive bladder cancer and treated with radical cystectomy at one of two institutions. SXR and MDR1 gene expression was assessed by real-time quantitative polymerase chain reaction (RT-PCR) in tumoral and normal tissue from frozen surgical specimens.


RESULTS
Patients were followed for a mean of 29 months; 31 patients (46%) had progression. In univariate analysis, significant predictors of overall survival (OS) were pathological stage, lymph node (LN) status, histological grade, vascular-lymphatic invasion, and SXR expression. In multivariate analysis, independent predictors of OS were LN status (odds ratio [OR], 2.96; P=0.034), vascular-lymphatic invasion (OR, 2.50; P=0.029), and SXR expression (OR, 1.05, P=0.03). Among the 51 patients with negative LNs (pN0), univariate predictors of OS were SXR expression, MDR1 expression, and pathological stage. In multivariate analysis, SXR expression (OR, 1.06; P=0.01) and MDR1 expression (OR, 3.27; P=0.03) were independently associated with survival. Within the pN0 group, patients with SXR expression had shorter progression-free survival than did those without expression (P=0.004). This association persisted in the N0 subgroup with stage pT3-pT4 disease (P=0.028). However, in the pN1 group SXR expression did not have any influence.


CONCLUSIONS
For patients with invasive bladder cancer, SXR expression has value as a predictor of survival independent of the standard pathological predictors. Its maximum importance appears to be in patients with stage pT3-pT4 pN0 disease.
Rioja
Jorge
J
Department of Urology, Clínica Universitaria Universidad de Navarra, Pamplona, Spain. jriojazu@gmail.com
Bandrés
Eva
E
Rosell Costa
David
D
Rincón
Anibal
A
López
Ines
I
Zudaire Bergera
Juan Javier
JJ
García Foncillas
Jesús
J
Gil
María Jesús
MJ
Panizo
Angel
A
Plaza
Luis
L
Rioja
Luis Angel
LA
Berián Polo
José María
JM
D000368:Aged; D000704:Analysis of Variance; D015331:Cohort Studies; D015653:Cystectomy / Q000379:methods* / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D016017:Odds Ratio; D000077297:Pregnane X Receptor; D011379:Prognosis; D011446:Prospective Studies; D011987:Receptors, Steroid / Q000235:genetics*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery
D000077297:Pregnane X Receptor; D011987:Receptors, Steroid