title: A prognostic model comprising pT stage, N status, and the chemokine receptors CXCR4 and CXCR7 powerfully predicts outcome in neoadjuvant resistant rectal cancer patients.
abstract: 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.
authors.affiliation: Department of Oncological Immunology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"-IRCCS-ITALIA, via M. Semmola, 80131, Naples, Italy.
authors.forename: Crescenzo
authors.initials: C
authors.lastname: D'Alterio
authors.forename: Antonio
authors.initials: A
authors.lastname: Avallone
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tatangelo
authors.forename: Paolo
authors.initials: P
authors.lastname: Delrio
authors.forename: Biagio
authors.initials: B
authors.lastname: Pecori
authors.forename: Laura
authors.initials: L
authors.lastname: Cella
authors.forename: Alessia
authors.initials: A
authors.lastname: Pelella
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: D'Armiento
authors.forename: Chiara
authors.initials: C
authors.lastname: Carlomagno
authors.forename: Franco
authors.initials: F
authors.lastname: Bianco
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Silvestro
authors.forename: Roberto
authors.initials: R
authors.lastname: Pacelli
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Rosario Vincenzo
authors.initials: RV
authors.lastname: Iaffaioli
authors.forename: Stefania
authors.initials: S
authors.lastname: Scala
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis; D054377:Chemokine CXCL12 / Q000378:metabolism; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D011836:Radiation Tolerance; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*
chemical_list: C501896:ACKR3 protein, human; D014408:Biomarkers, Tumor; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4
keywords: CXCR4; outcome; predictive model; preoperative radio chemotherapy; rectal cancer