10.3389/fonc.2019.01243.s007
Bowen Bao
Bowen
Bao
Chunlei Zheng
Chunlei
Zheng
Bowen Yang
Bowen
Yang
Yue Jin
Yue
Jin
Kezuo Hou
Kezuo
Hou
Zhi Li
Zhi
Li
Xueying Zheng
Xueying
Zheng
Shitong Yu
Shitong
Yu
Xiaojie Zhang
Xiaojie
Zhang
Yibo Fan
Yibo
Fan
Xiujuan Qu
Xiujuan
Qu
Yunpeng Liu
Yunpeng
Liu
Xiaofang Che
Xiaofang
Che
Table_3_Identification of Subtype-Specific Three-Gene Signature for Prognostic Prediction in Diffuse Type Gastric Cancer.XLSX
Frontiers
2019
gastric cancer
diffuse type
signature
nomogram
peritoneal metastasis
2019-11-12 04:13:00
Dataset
https://frontiersin.figshare.com/articles/dataset/Table_3_Identification_of_Subtype-Specific_Three-Gene_Signature_for_Prognostic_Prediction_in_Diffuse_Type_Gastric_Cancer_XLSX/10287584
<p>Gastric cancer (GC), with high heterogeneity, can be mainly classified into intestinal type and diffuse type according to the Lauren classification system. Although a number of differences were reported between these two types, no study on the Lauren subtype-specific multi-gene signature for evaluation of GC prognosis has been conducted, and the molecular mechanism underlying its poor prognosis has still remained elusive. Therefore, this study aimed to explore subtype-specific multi-gene signature for prognostic prediction in different subtypes of Lauren classification. With combination of the least absolute shrinkage and selection operator (LASSO) algorithm and the Akaike information criterion (AIC), the 3-gene subtype-specific prognostic signature was successfully established in diffuse type GC using GSE62254 dataset. Following the calculation of risk score (RS) based on 3-gene signature, the nomogram models were established to predict 1-, 3-, and 5-year overall survival in diffuse type GC. Moreover, the prognostic predictive nomogram model of diffuse type GC was also proved to be effective for validation of GSE1549 dataset and by a Gene Expression Omnibus (GEO)-based meta-analysis. In the analysis of the correlation between RS and clinical-pathological characteristics, RS and two genes of the 3-gene signature (EMCN and COL4A5) were found to be positively correlated with peritoneal metastasis. Furthermore, EMCN and COL4A5, rather than CCL11, were proved to be able to enhance the adhesion ability of MKN45 and NUGC4 cells to peritoneal mesothelial cell line HMR-SV5. Eventually, it was proved that COL4A5 promoted peritoneal metastasis by activating Wnt signaling pathway, whereas the upregulation of integrin family genes mediated by FAK-AKT/ERK/STAT3 signaling pathway activation is involved in peritoneal metastasis promotion function of EMCN. Taken together, our study identified the subtype-specific 3-gene signature in diffuse type GC, which could effectively predict the patients' OS and might explain the molecular mechanisms in presence of its poor prognosis.</p>