title: Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study.
abstract: Neoadjuvant 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.
  
  
  
  Sixty-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.
  
  
  
  Univariate 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).
  
  
  
  This 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.
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Del Puerto-Nevado
authors.affiliation: Radiotherapy Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avda Reyes Catolicos, 2, Madrid, 28040, Spain.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Marin-Arango
authors.affiliation: Pathology Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, Madrid, 28040, Spain.|Present address at University Hospital Clinico San Carlos, Profesor Martin Lagos, S/N, Madrid, 28040, Spain.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Fernandez-Aceñero
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Arroyo-Manzano
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Useros
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Aurea
authors.initials: A
authors.lastname: Borrero-Palacios
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Rodriguez-Remirez
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Cebrian
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gomez Del Pulgar
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Marlid
authors.initials: M
authors.lastname: Cruz-Ramos
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Carames
authors.affiliation: Radiotherapy Department, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avda Reyes Catolicos, 2, Madrid, 28040, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Lopez-Botet
authors.affiliation: Translational Oncology Division, Oncohealth Institute, Health Research Institute FJD-UAM, University Hospital "Fundacion Jimenez Diaz", Avenida Reyes Catolicos, 2, 28040, Madrid, Spain. jesus.garciafoncillas@oncohealth.eu.
authors.forename: Jesús
authors.initials: J
authors.lastname: Garcia-Foncillas
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000628:therapy; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000628:therapy; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C109890:VRK1 protein, human; C109891:VRK2 protein, human
keywords: Chemoradiotherapy; Composite score; NACRT; Nomogram; Rectal cancer; Tumor response; VRK1; VRK2