Dataset Information

Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer.

ABSTRACT:

Purpose

This study was aimed at developing and validating a quantitative multigene assay for predicting tumor recurrence after gastric cancer surgery.

Experimental design

Gene expression data were generated from tumor tissues of patients who underwent surgery for gastric cancer (n = 267, training cohort). Genes whose expression was significantly associated with activation of YAP1 (a frequently activated oncogene in gastrointestinal cancer), 5-year recurrence-free survival, and 5-year overall survival were first identified as candidates for prognostic genes (156 genes, P < 0.001). We developed the recurrence risk score (RRS) by using quantitative RT-PCR to identify genes whose expression levels were significantly associated with YAP1 activation and patient survival in the training cohort.

Results

We based the RRS assay on 6 genes, IGFBP4, SFRP4, SPOCK1, SULF1, THBS, and GADD45B, whose expression levels were significantly associated with YAP1 activation and prognosis in the training cohort. The RRS assay was further validated in an independent cohort of 317 patients. In multivariate analysis, the RRS was an independent predictor of recurrence [HR, 1.6; 95% confidence interval (CI), 1.02-2.4; P = 0.03]. In patients with stage II disease, the RRS had an HR of 2.9 (95% CI, 1.1-7.9; P = 0.03) and was the only significant independent predictor of recurrence.

Conclusions

The RRS assay was a valid predictor of recurrence in the two cohorts of patients with gastric cancer. Independent prospective studies to assess the clinical utility of this assay are warranted. Clin Cancer Res; 22(24); 6228-35. ©2016 AACR.

SUBMITTER: Lee KW

PROVIDER: S-EPMC5458637 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer.

Lee Keun-Wook KW Lee Sung Sook SS Hwang Jun-Eul JE Jang Hee-Jin HJ Lee Hyun-Sung HS Oh Sang Cheul SC Lee Sang Ho SH Sohn Bo Hwa BH Kim Sang Bae SB Shim Jae-Jun JJ Jeong Woojin W Cha Minse M Cheong Jae-Ho JH Cho Jae Yong JY Lim Jae Yun JY Park Eun Sung ES Kim Sang Cheol SC Kang Yoon-Koo YK Noh Sung Hoon SH Ajani Jaffer A JA Lee Ju-Seog JS

Clinical cancer research : an official journal of the American Association for Cancer Research 20160921 24

<h4>Purpose</h4>This study was aimed at developing and validating a quantitative multigene assay for predicting tumor recurrence after gastric cancer surgery.<h4>Experimental design</h4>Gene expression data were generated from tumor tissues of patients who underwent surgery for gastric cancer (n = 267, training cohort). Genes whose expression was significantly associated with activation of YAP1 (a frequently activated oncogene in gastrointestinal cancer), 5-year recurrence-free survival, and 5-y ...[more]

PMID: 27654712

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Project description:ObjectivesCellulitis is often treated with antibiotics for longer than recommended by guidelines. Prolonged therapy may reduce recurrence in certain patients, but it is not known which patients are at greatest risk. Our objective was to develop and temporally validate a risk prediction score to identify patients attending hospital with cellulitis at highest risk of recurrence.MethodsWe included UK adult patients with cellulitis attending hospital in an electronic health records (EHR) study to identify demographic, comorbid, physiological, and laboratory factors predicting recurrence (before death) within 90 days, using multivariable logistic regression with backwards elimination in complete cases. A points-based risk score integerised model coefficients for selected predictors. Performance was assessed using the C-index in development and temporal validation samples.ResultsThe final model included 4938 patients treated for median 8 days (IQR 6-11); 8.8% (n = 436) experienced hospitalisation-associated recurrence. A risk score using eight variables (age, heart rate, urea, platelets, albumin, previous cellulitis, venous insufficiency, and liver disease) ranged from 0-15, with C-index = 0.65 (95%CI: 0.63-0.68). Categorising as low (score 0-1), medium (2-5) and high (6-15) risk, recurrence increased fourfold; 3.2% (95%CI: 2.3-4.4%), 9.7% (8.7-10.8%), and 16.6% (13.3-20.4%). Performance was maintained in the validation sample (C-index = 0.63 (95%CI: 0.58-0.67)). Among patients at high risk, four distinct clinical phenotypes were identified using hierarchical clustering 1) young, acutely unwell with liver disease; 2) comorbid with previous cellulitis and venous insufficiency; 3) chronic renal disease with severe renal impairment; and 4) acute severe illness, with substantial inflammatory responses.ConclusionsRisk of cellulitis recurrence varies markedly according to individual patient factors captured in the Baseline Recurrence Risk in Cellulitis (BRRISC) score. Further work is needed to optimise the score, considering baseline and treatment response variables not captured in EHR data, and establish the utility of risk-based approaches to guide optimal antibiotic duration.

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Dataset Information

Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer.

Purpose

Experimental design

Results

Conclusions

Publications

Development and Validation of a Six-Gene Recurrence Risk Score Assay for Gastric Cancer.

Similar Datasets

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