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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

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

Authors: Laura del Puerto-Nevado, Juan Pablo Marin-Arango, Maria Jesus Fernandez-Aceñero, David Arroyo-Manzano, Javier Martinez-Useros, Aurea Borrero-Palacios, Maria Rodriguez-Remirez, Arancha Cebrian, Teresa Gomez del Pulgar, Marlid Cruz-Ramos, Cristina Carames, Begoña Lopez-Botet, Jesús Garcia-Foncillas

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

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.
Appendix
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Metadata
Title
Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study
Authors
Laura del Puerto-Nevado
Juan Pablo Marin-Arango
Maria Jesus Fernandez-Aceñero
David Arroyo-Manzano
Javier Martinez-Useros
Aurea Borrero-Palacios
Maria Rodriguez-Remirez
Arancha Cebrian
Teresa Gomez del Pulgar
Marlid Cruz-Ramos
Cristina Carames
Begoña Lopez-Botet
Jesús Garcia-Foncillas
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2574-9

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