Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2574-9) contains supplementary material, which is available to authorized users.
Highlights
Neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection is the standard therapy for locally advanced rectal cancer
Neoadjuvant chemoradiation therapy (NACRT) followed by surgical resection is widely accepted as the standard therapeutic algorithm for locally advanced rectal cancer [1, 2]
The group of vaccinia-related kinases received its name from vaccinia virus B1R, a serine/threonine kinase present in infecting virions which is essential for viral DNA synthesis [8]
Summary
Neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection is the standard therapy for locally advanced rectal cancer. Neoadjuvant chemoradiation therapy (NACRT) followed by surgical resection is widely accepted as the standard therapeutic algorithm for locally advanced rectal cancer [1, 2]. A wide range of tumor responses has been shown following NACRT, ranging from pathologic complete response to progression of the disease. The universally accepted clinicopathological variables for assessing tumor response after neoadjuvant treatment are tumor regression grade (TRG) and tumor downstaging [3]. The evaluation of both parameters has been highly associated to sphincter preservation following curative resection in these patients [4, 5]. The mammalian kinase family comprises three members: VRK1, VRK2, and the catalytically inert VRK3 [10]
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