Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study

BMC Cancer

Research Article

David Arroyo-Manzano¹  Maria Jesus Fernandez-Aceñero²  Begoña Lopez-Botet³  Juan Pablo Marin-Arango³  Marlid Cruz-Ramos⁴  Javier Martinez-Useros⁴  Maria Rodriguez-Remirez⁴  Teresa Gomez del Pulgar⁴  Cristina Carames⁴  Aurea Borrero-Palacios⁴  Jesús Garcia-Foncillas⁴  Laura del Puerto-Nevado⁴  Arancha Cebrian⁴ 

[1] Clinical Biostatistics Unit, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Carretera de Colmenar Viejo km. 9,100, 28034 Madrid, Spain and CIBER of Epidemiology and Public Health (CIBERESP), C/Melchor Fernández Almagro, 3-5, Madrid, Spain;Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital “Fundacion Jimenez Diaz”, Avenida Reyes Catolicos, 2, 28040, Madrid, Spain;Present address at University Hospital Clinico San Carlos, Profesor Martin Lagos, S/N, 28040, Madrid, Spain;Radiotherapy Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital “Fundacion Jimenez Diaz”, Avda Reyes Catolicos, 2, 28040, Madrid, Spain;Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital “Fundacion Jimenez Diaz”, Avenida Reyes Catolicos, 2, 28040, Madrid, Spain;

关键词: VRK1;    VRK2;    Rectal cancer;    Chemoradiotherapy;    Tumor response;    Nomogram;    Composite score;    NACRT;   

DOI  :  10.1186/s12885-016-2574-9

 received in 2016-02-16, accepted in 2016-07-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundNeoadjuvant chemoradiotherapy (NACRT) followed by surgical resection is the standard therapy for locally advanced rectal cancer. However, tumor response following NACRT varies, ranging from pathologic complete response to disease progression. We evaluated the kinases VRK1 and VRK2, which are known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis, and as such are potential predictors of tumor response and may aid in identifying patients who could benefit from NACRT.MethodsSixty-seven pretreatment biopsies were examined for VRK1 and VRK2 expression using tissue microarrays. VRK1 and VRK2 Histoscores were combined by linear addition, resulting in a new variable designated as “composite score”, and the statistical significance of this variable was assessed by univariate and multivariate logistic regression. The Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC) analysis were carried out to evaluate calibration and discrimination, respectively. A nomogram was also developed.ResultsUnivariate logistic regression showed that tumor size as well as composite score were statistically significant. Both variables remained significant in the multivariate analysis, obtaining an OR for tumor size of 0.65 (95 % CI, 0.45–0.94; p = 0.021) and composite score of 1.24 (95 % CI, 1.07–1.48; p = 0.005). Hosmer-Lemeshow test showed an adequate model calibration (p = 0.630) and good discrimination was also achieved, AUC 0.79 (95 % CI, 0.68–0.90).ConclusionsThis study provides novel data on the role of VRK1 and VRK2 in predicting tumor response to NACRT, and we propose a model with high predictive ability which could have a substantial impact on clinical management of locally advanced rectal cancer.

【 授权许可】

CC BY   
© The Author(s). 2016