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. 2017 Aug 7;8(39):66305-66315.
doi: 10.18632/oncotarget.19985. eCollection 2017 Sep 12.

Development of mesenchymal subtype gene signature for clinical application in gastric cancer

Jeeyun Lee  1 , Razvan Cristescu  2 , Kyoung-Mee Kim  3 , Kyung Kim  1 , Seung Tae Kim  1 , Se Hoon Park  1 , Won Ki Kang  1
Affiliations

Development of mesenchymal subtype gene signature for clinical application in gastric cancer

Jeeyun Lee et al. Oncotarget. .

Abstract

Previously, in the Asian Cancer Research Group (ACRG) project, we defined four distinct molecular subtypes in gastric cancer (GC). Mesenchymal (microsatellite stable with epithelial-to-mesenchymal transition phenotype, MSS/EMT) tumors showed the worst prognosis among all the subtypes. To develop a gene signature for predicting mesenchymal subtype GC, we conducted gene expression profiling using a NanoString assay in 70 ACRG specimens. The gene signature was validated in an independent set obtained from the prospective Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. The association between the mesenchymal subtype and survival was investigated. After cross-platform concordance test performed in 70 ACRG specimens, a 71-gene MSS/EMT signature was obtained. In the validation set, the gene signature predicted that 20 of 73 (27%) patients had mesenchymal tumors. Patients with mesenchymal subtype had diffuse GC, poorly-differentiated or signet ring cell carcinoma, and were microsatellite stable. The estimated hazard ratio for survival in patients with mesenchymal GC compared to those with non-mesenchymal tumors was 2.262 (95% confidence interval, 1.410 to 3.636; P=0.001). The survival difference remained significant when the subtypes were analyzed according to clinical prognostic parameters. This study suggested that the NanoString-based 71-gene signature for mesenchymal subtype is a strong predictor of the outcome in patients with GC.

Keywords: gene signature; genomics; mesenchymal; stomach neoplasm; subtypes.

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Figures

Figure 1
Figure 1. Study design to explore and validate gene signature for mesenchymal subtype
EMT, epithelial-to-mesenchymal transition; ACRG, Asian Cancer Research Group; ARTIST, Adjuvant chemoRadiotherapy In Stomach Tumor.
Figure 2
Figure 2. Concordance test subtypes classified by Affymetrix gene expression profiling and mesenchymal subtype by NanoString
Figure 3
Figure 3
(A) Overall survival of the ARTIST patients (n=73) according to the NanoString mesenchymal scores. Solid line, non-mesenchymal (bottom 75% scores). (B) Overall survival of all (ARTIST/ACRG combined) patients (n=143) according to the NanoString mesenchymal scores. Solid line, non-mesenchymal (bottom 75% scores); dotted line, mesenchymal (top 25% scores).
See this image and copyright information in PMC

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