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Development and Evaluation of a Clinically Applicable 53-Gene Prognostic Assay in Gastric Cancer: A Multicenter Study
36 Pages Posted: 14 Jul 2020
More...Abstract
Background: We previously established a 53-gene prognostic signature for predicting overall survival (OS) of patients with gastric adenocarcinoma. Here we aimed to develop a clinically applicable assay for quantifying mRNA of 53 genes and to validate the prognostic significance of this signature in a retrospective multi-centered study.
Methods: We developed a mRNA hybridization-based 53-gene expression assay applicable to formalin-fixed paraffin-embedded (FFPE) tissues. Total 540 patients were enrolled in the study from three hospitals between 2008-2013. 180 patents from two hospitals were randomly selected to build a prognostic prediction model based on the 53-gene signature using leave-p-out (one-third out) cross-validation method (resample 100 times) together with Cox regression and Kaplan-Meier analysis, and the model was tested in the independent cohorts, a total of 360 gastric cancer patients.
Findings: The mRNA detection assay reliably and sensitively quantified the expression of 53 prognostic genes plus 5 reference genes in FFPE specimens. The prognostic scores were generated using the developed assay in 100 sampling training sets (n=120) and were significantly associated with OS in 100 sampling validation sets (N=60). The significant association of prognostic scores with OS was held in independent hospital cohorts or their pooled cohort. Moreover, the multivariate Cox regression demonstrated that the predictive power of the prognostic scores was independent of patient age, gender and stage. The scores were predictive factor for OS at each clinical stage.
Interpretation: This assay can provide a reliable and sensitive platform for high-throughput gene expression profiling in FFPE samples. The 53-gene prognostic score is clinically applicable for predicting OS of patients with different stages of gastric cancer. Funding National Science and Technology Major Special Project; National Natural Science Foundation of China; and Natural Science Foundation from the Department of Science & Technology of Jiangsu Province.
Funding Statement: This work was supported by grants from the National Science and Technology Major Special Project (No. 2018ZX09201016), the National Natural Science Foundation of China (No. 81802388), and the Natural Science Foundation from the Department of Science & Technology of Jiangsu Province (No. BK20180120).
Declaration of Interests: All authors declare that they have no conflict of interest.
Ethics Approval Statement: This study was approved by the Ethics Committees of the individual hospitals participated, and informed general consent was obtained from each patient.
Keywords: gastric cancer: gastric adenocarcinoma; prognostic gene signature; a multigene expression assay; leave-p-out cross-validation; overall survival
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