Dataset Information

MAP2K6 is associated with radiation resistance and adverse prognosis for locally advanced nasopharyngeal carcinoma patients.

ABSTRACT: Background:Although radiotherapy is the primary therapeutic option for nasopharyngeal carcinoma (NPC), local recurrence and distant metastasis caused by radioresistance are still the major barriers for some NPC patients who cannot benefit from radiotherapy. In this study, we analyzed the association between MAP2K6 expression and radioresistance in patients with locally advanced NPC. Methods:We collected 120 NPC patients who received radiotherapy in the Xiangya Hospital of Central South University from August 2008 to July 2012. The clinical data and tissue samples of patients were collected. Detection of MAP2K6 was performed using immunohistochemical staining. Results:The rates of two groups were 19.4% and 4.2%, and significant difference was observed between MAP2K6 high expression group and low expression group (?2=5.817, P=0.016). The Kaplan-Meier analysis suggested a significant difference in the survival rate between two groups (P<0.05). The results from multivariate Cox regression indicated that the MAP2K6 was independently related to adverse prognosis in NCP patients (HR =3.40, 95% CI =1.13-10.26, P=0.030). Conclusion:The present study indicated that MAP2K6 was correlated with radioresistance, and the elevated expression of MAP2K6 predicted poor prognosis in NPC patients. MAP2K6 may be a new therapy target for radioresistance of NPC.

SUBMITTER: Li Z

PROVIDER: S-EPMC6296680 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MAP2K6 is associated with radiation resistance and adverse prognosis for locally advanced nasopharyngeal carcinoma patients.

Li Zhanzhan Z Li Na N Shen Liangfang L

Cancer management and research 20181212

<h4>Background</h4>Although radiotherapy is the primary therapeutic option for nasopharyngeal carcinoma (NPC), local recurrence and distant metastasis caused by radioresistance are still the major barriers for some NPC patients who cannot benefit from radiotherapy. In this study, we analyzed the association between MAP2K6 expression and radioresistance in patients with locally advanced NPC.<h4>Methods</h4>We collected 120 NPC patients who received radiotherapy in the Xiangya Hospital of Central ...[more]

PMID: 30588096

Similar Datasets

Project description:BackgroundTo investigate the feasibility of a knowledge-based automated intensity-modulated radiation therapy (IMRT) planning technique for locally advanced nasopharyngeal carcinoma (NPC) radiotherapy.MethodsOne hundred forty NPC patients treated with definitive radiation therapy with the step-and-shoot IMRT techniques were retrospectively selected and separated into a knowledge library (n = 115) and a test library (n = 25). For each patient in the knowledge library, the overlap volume histogram (OVH), target volume histogram (TVH) and dose objectives were extracted from the manually generated plan. 5-fold cross validation was performed to divide the patients in the knowledge library into 5 groups before validating one group by using the other 4 groups to train each neural network (NN) machine learning models. For patients in the test library, their OVH and TVH were then used by the trained models to predict a corresponding set of mean dose objectives, which were subsequently used to generate automated plans (APs) in Pinnacle planning system via an in-house developed automated scripting system. All APs were obtained after a single step of optimization. Manual plans (MPs) for the test patients were generated by an experienced medical physicist strictly following the established clinical protocols. The qualities of the APs and MPs were evaluated by an attending radiation oncologist. The dosimetric parameters for planning target volume (PTV) coverage and the organs-at-risk (OAR) sparing were also quantitatively measured and compared using Mann-Whitney U test and Bonferroni correction.ResultsAPs and MPs had the same rating for more than 80% of the patients (19 out of 25) in the test group. Both AP and MP achieved PTV coverage criteria for no less than 80% of the patients. For each OAR, the number of APs achieving its criterion was similar to that in the MPs. The AP approach improved planning efficiency by greatly reducing the planning duration to about 17% of the MP (9.85 ± 1.13 min vs. 57.10 ± 6.35 min).ConclusionA robust and effective knowledge-based IMRT treatment planning technique for locally advanced NPC is developed. Patient specific dose objectives can be predicted by trained NN models based on the individual's OVH and clinical TVH goals. The automated planning scripts can use these dose objectives to efficiently generate APs with largely shortened planning time. These APs had comparable dosimetric qualities when compared to our clinic's manual plans.

Project description:PurposeConcurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta-analysis investigates the value of adding ICT to CCRT in LA-NPC.Materials and methodsTwo reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment-naive adult patients with histologically proven nonmetastatic LA-NPC.ResultsEight RCTs with in total 2,384 randomized patients, of whom 69% had N2-N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%-100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) -0.001-0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, -0.243; 95% CI, -0.403 to -0.083; p = .003). Grade 3-4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511-0.905; p = .001) and progression-free survival (HR, 0.657; 95% CI, 0.568-0.760; p < .001).ConclusionAlthough ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA-NPC, but further study on optimal patient selection for this treatment is warranted.Implications for practiceLocally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta-analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA-NPC is associated with a significant clinical improvement in both overall survival and progression-free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA-NPC.

Project description:BackgroundAlthough the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study.MethodsThis retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18-70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the β regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors.ResultsThe median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients.ConclusionsCompared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.

Project description:Background: Recurrence remains one of the key reasons of relapse after the radical radiation for locally advanced nasopharyngeal carcinoma (NPC). Here, the multiple molecular and clinical variables integrated decision tree algorithms were designed to predict individual recurrence patterns (with VS without recurrence) for locally advanced NPC. Methods: A total of 136 locally advanced NPC patients retrieved from a randomized controlled phase III trial, were included. For each patient, the expression levels of 33 clinicopathological biomarkers in tumor specimen, 3 Epstein-Barr virus related serological antibody titer and 5 clinicopathological variables, were detected and collected to construct the decision tree algorithm. The expression level of 33 clinicopathological biomarkers in tumor specimen was evaluated by immunohistochemistry staining. Results: Three algorithm classifiers, augmented by the adaptive boosting algorithm for variable selection and classification, were designed to predict individual recurrence pattern. The classifiers were trained in the training subset and further tested using a 10-fold cross-validation scheme in the validation subset. In total, 13 molecules expression level in tumor specimen, including AKT1, Aurora-A, Bax, Bcl-2, N-Cadherin, CENP-H, HIF-1α, LMP-1, C-Met, MMP-2, MMP-9, Pontin and Stathmin, and N stage were selected to construct three 10-fold cross-validation decision tree classifiers. These classifiers showed high predictive sensitivity (87.2-93.3%), specificity (69.0-100.0%), and overall accuracy (84.5-95.2%) to predict recurrence pattern individually. Multivariate analyses confirmed the decision tree classifier was an independent prognostic factor to predict individual recurrence (algorithm 1: hazard ration (HR) 0.07, 95% confidence interval (CI) 0.03-0.16, P < 0.01; algorithm 2: HR 0.13, 95% CI 0.04-0.44, P < 0.01; algorithm 3: HR 0.13, 95% CI 0.03-0.68, P = 0.02). Conclusion: Multiple molecular and clinicopathological variables integrated decision tree algorithms may individually predict the recurrence pattern for locally advanced NPC. This decision tree algorism provides a potential tool to select patients with high recurrence risk for intensive follow-up, and to diagnose recurrence at an earlier stage for salvage treatment in the NPC endemic region.

Dataset Information

MAP2K6 is associated with radiation resistance and adverse prognosis for locally advanced nasopharyngeal carcinoma patients.

Publications

MAP2K6 is associated with radiation resistance and adverse prognosis for locally advanced nasopharyngeal carcinoma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets