Dataset Information

Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases.

ABSTRACT:

Background and objectives

This study was designed to identify and validate gene signatures that can predict disease free survival (DFS) in patients undergoing a radical resection for their colorectal liver metastases (CRLM).

Methods

Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France) and the University Medical Center Utrecht (The Netherlands). Patients were divided into high and low risk groups. A randomly selected training set was used to find predictive gene signatures. The ability of these gene signatures to predict DFS was tested in an independent validation set comprising the remaining patients. Furthermore, 5 known clinical risk scores were tested in our complete patient cohort.

Result

No gene signature was found that significantly predicted DFS in the validation set. In contrast, three out of five clinical risk scores were able to predict DFS in our patient cohort.

Conclusions

No gene signature was found that could predict DFS in patients undergoing CRLM resection. Three out of five clinical risk scores were able to predict DFS in our patient cohort. These results emphasize the need for validating risk scores in independent patient groups and suggest improved designs for future studies.

SUBMITTER: Snoeren N

PROVIDER: S-EPMC3504021 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases.

Snoeren Nikol N van Hooff Sander R SR Adam Rene R van Hillegersberg Richard R Voest Emile E EE Guettier Catherine C van Diest Paul J PJ Nijkamp Maarten W MW Brok Mariel O MO van Leenen Dik D Koerkamp Marian J A Groot MJ Holstege Frank C P FC Rinkes Inne H M Borel IH

PloS one 20121121 11

<h4>Background and objectives</h4>This study was designed to identify and validate gene signatures that can predict disease free survival (DFS) in patients undergoing a radical resection for their colorectal liver metastases (CRLM).<h4>Methods</h4>Tumor gene expression profiles were collected from 119 patients undergoing surgery for their CRLM in the Paul Brousse Hospital (France) and the University Medical Center Utrecht (The Netherlands). Patients were divided into high and low risk groups. A ...[more]

PMID: 23185333

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Project description:ImportanceIschemia-reperfusion injury during hepatic resection has been shown to accelerate progression of liver cancer. However, the prognostic relevance of remnant liver ischemia (RLI) after resection of colorectal liver metastases (CLMs) is unknown to date.ObjectivesTo assess the prognostic influence of RLI after resection of CLMs and to identify correlates of greater extent of RLI.Design, setting, and participantsThis study was a retrospective analysis at The University of Texas MD Anderson Cancer Center based on prospectively collected data. The study identified 202 patients who underwent curative resection of CLMs between January 1, 2008, and December 31, 2014, and had enhanced computed tomographic images obtained within 30 days after surgery.Main outcomes and measuresRemnant liver ischemia was defined as reduced or absent contrast enhancement during the portal phase. Postoperative RLI was classified as grade 0 (none), 1 (marginal), 2 (partial), 3 (segmental), or 4 (necrotic) as previously defined. Experienced members of the surgical team retrospectively performed imaging assessments. Team members were masked to the postoperative outcomes. Survival after resection was stratified by RLI grade. Predictors of RLI grade 2 or higher and survival were identified.ResultsAmong 202 patients (median [range] age, 56 [27-87] years; 84 female), the RLI grades were as follows: grade 0 (105 patients), grade 1 (47 patients), grade 2 (45 patients), grade 3 (5 patients), and grade 4 (0 patients). Recurrence-free survival (RFS) and cancer-specific survival (CSS) rates after hepatic resection were worse in patients with RLI grade 2 or higher vs grade 1 or lower (RFS at 3 years, 6.4% [3 of 50] vs 39.2% [60 of 152]; P < .001 and CSS at 5 years, 20.7% [10 of 50] vs 63.7% [97 of 152]; P < .001). A largest metastasis at least 3 cm (OR, 2.74; 95% CI, 1.35-5.70; P = .005), multiple CLMs (OR, 2.51; 95% CI, 1.25-5.24; P = .009), and nonanatomic resection (odds ratio [OR], 3.29; 95% CI, 1.52-7.63; P = .002) were associated with RLI grade 2 or higher. A largest metastasis at least 3 cm (hazard ratio [HR], 1.70; 95% CI, 1.01-2.88; P = .045), mutant RAS (HR, 2.15; 95% CI, 1.27-3.64; P = .005), and RLI grade 2 or higher (HR, 2.90; 95% CI, 1.69-4.84; P < .001) were associated with worse CSS.Conclusions and relevanceIn this study, remnant liver ischemia grade 2 or higher was associated with worse CSS after resection of CLMs. High-quality anatomic surgery to minimize RLI after resection is essential.

Project description:BackgroundMost current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables.MethodsA prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort.ResultsA total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases.ConclusionThe contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.

Dataset Information

Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases.

Background and objectives

Methods

Result

Conclusions

Publications

Exploring gene expression signatures for predicting disease free survival after resection of colorectal cancer liver metastases.

Similar Datasets

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