Dataset Information

Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer.

ABSTRACT: Neoadjuvant chemotherapy (NACT) has been an increasingly used therapeutic strategy to improve the outcome of advanced gastric cancer (GC) over the past few decades. Lymphocytic infiltration has been reported to be associated with response to NACT, but the immune cell subpopulation and its prognosis contributing to response in GC have not been clarified yet. In the current study, the tumor infiltration of FOXP3+ and GARP+ regulatory T-cells (Tregs, marked by FOXP3 and GARP) response to NACT in advanced GC and their correlation with prognosis were evaluated. The infiltration of FOXP3+ and GARP+ Tregs in 102 patients with advanced GC who were treated with or without NACT was measured using immunohistochemical method. The infiltration of FOXP3+ and GARP+ Tregs was significantly decreased in the NACT group than in the non-NACT group (P=0.023 and P=0.012, respectively) and significantly associated with tumor, node, metastasis stage (P=0.019 and P=0.011, respectively). There was no significant difference in patient's overall survival between the NACT and non-NACT groups (P=0.166); however, patients in the NACT group with decreased infiltration of FOXP3+ and GARP+ Tregs had longer overall survival (P=0.002 and P<0.001, respectively). Univariate and multivariate analyses indicated that the infiltration of GARP+ Tregs and lymph node metastasis were independent prognostic factors (P=0.038 and P=0.013, respectively). The results demonstrated that NACT could decrease the infiltration of FOXP3+ and GARP+ Tregs, and that the infiltration of GARP+ Tregs may serve as a new prognostic factor of human GC response to NACT.

SUBMITTER: Li K

PROVIDER: S-EPMC4913533 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer.

Li Kai K Chen Fuchao F Xie Huijuan H

OncoTargets and therapy 20160614

Neoadjuvant chemotherapy (NACT) has been an increasingly used therapeutic strategy to improve the outcome of advanced gastric cancer (GC) over the past few decades. Lymphocytic infiltration has been reported to be associated with response to NACT, but the immune cell subpopulation and its prognosis contributing to response in GC have not been clarified yet. In the current study, the tumor infiltration of FOXP3+ and GARP+ regulatory T-cells (Tregs, marked by FOXP3 and GARP) response to NACT in ad ...[more]

PMID: 27366089

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Project description:BackgroundSerum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery.MethodsIn total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher's exact test. Multivariate analyses were performed by the Cox regression model.ResultsPre- and post-CA199, -CA125 and -CA724 could predict overall survival (all P < 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, -CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P < 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05).ConclusionsCA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.

Project description:ObjectivesTo develop and evaluate machine learning models using baseline and restaging computed tomography (CT) for predicting and early detecting pathological downstaging (pDS) with neoadjuvant chemotherapy in advanced gastric cancer (AGC).MethodsWe collected 292 AGC patients who received neoadjuvant chemotherapy. They were classified into (a) primary cohort (206 patients with 3-4 cycles chemotherapy) for model development and internal validation, (b) testing cohort I (46 patients with 3-4 cycles chemotherapy) for evaluating models' predictive ability before and after the complete course, and (c) testing cohort II (n = 40) for model evaluation on its performance at early treatment. We extracted 1,231 radiomics features from venous phase CT at baseline and restaging. We selected radiomics models based on 28 cross-combination models and measured the areas under the curve (AUC). Our prediction radiomics (PR) model is designed to predict pDS outcomes using baseline CT. Detection radiomics (DR) model is applied to restaging CT for early pDS detection.ResultsPR model achieved promising outcomes in two testing cohorts (AUC 0.750, p = .009 and AUC 0.889, p = .000). DR model also showed a good predictive ability (AUC 0.922, p = .000 and AUC 0.850, p = .000), outperforming the commonly used RECIST method (NRI 39.5% and NRI 35.4%). Furthermore, the improved DR model with averaging outcome scores of PR and DR models showed boosted results in two testing cohorts (AUC 0.961, p = .000 and AUC 0.921, p = .000).ConclusionsCT-based radiomics models perform well on prediction and early detection tasks of pDS and can potentially assist surgical decision-making in AGC patients.Key points• Baseline contrast-enhanced computed tomography (CECT)-based radiomics features were predictive of pathological downstaging, allowing accurate identification of non-responders before therapy. • Restaging CECT-based radiomics features were predictive to achieve pDS after and even at an early stage of neoadjuvant chemotherapy. • Combination of baseline and restaging CECT-based radiomics features was promising for early detection and preoperative evaluation of pathological downstaging of AGC.

Dataset Information

Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer.

Publications

Decreased FOXP3+ and GARP+ Tregs to neoadjuvant chemotherapy associated with favorable prognosis in advanced gastric cancer.

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