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A prognostic model comprising pT stage, N status, and the chemokine receptors CXCR4 and CXCR7 powerfully predicts outcome in neoadjuvant resistant rectal cancer patients
Author(s) -
D'Alterio Crescenzo,
Avallone Antonio,
Tatangelo Fabiana,
Delrio Paolo,
Pecori Biagio,
Cella Laura,
Pelella Alessia,
D'Armiento Francesco Paolo,
Carlomagno Chiara,
Bianco Franco,
Silvestro Lucrezia,
Pacelli Roberto,
Napolitano Maria,
Iaffaioli Rosario Vincenzo,
Scala Stefania
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28689
Subject(s) - cxcr4 , medicine , colorectal cancer , oncology , stage (stratigraphy) , chemokine receptor , chemoradiotherapy , chemokine , cancer , adjuvant therapy , metastasis , adjuvant , receptor , biology , paleontology
Despite the optimization of the local treatment of advanced rectal cancer (LARC), combination of preoperative chemoradiotherapy (CRT) and surgery, approximately one third of patients will develop distant metastases. Since the chemokine receptor CXCR4 has been implicated in metastasis development and prognosis in colorectal cancer, the role of the entire axis CXCR4‐CXCL12‐CXCR7 was evaluated to identify high relapse risk rectal cancer patients. Tumor specimens of 68 LARC patients undergoing surgery after neoadjuvant‐CRT were evaluated for CXCR4, CXCR7, and CXCL12 expression through immunohistochemistry. Multivariable prognostic model was developed using classical prognostic factors along with chemokine receptor expression profiles. High CXCR4 correlated with a shorter relapse‐free survival (RFS) ( p = 0.0006) and cancer specific survival (CSS) ( p = 0.0004). Concomitant high CXCR4‐negative/low CXCR7 or high CXCR4‐negative/low CXCL12 significantly impaired RFS ( p = 0.0003 and p = 0.0043) and CSS ( p = 0.0485 and p = 0.0026). High CXCR4/N+ identified the worst prognostic category for RFS ( p < 0.0001) and CSS ( p = 0.0003). The optimal multivariable predictive model for RFS was a five‐variable model consisting of gender, pT stage, N status, CXCR4, and CXCR7 (AUC = 0.92, 95% CI = 0.77–0.98). The model is informative and supportive for adjuvant treatment and identifies CXCR4 as a new therapeutic target in rectal cancer.© 2013 UICC