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pmid:31803620
Identification of Subtype-Specific Three-Gene Signature for Prognostic Prediction in Diffuse Type Gastric Cancer.
Bowen Bao · Chunlei Zheng · Bowen Yang · Yue Jin · Kezuo Hou · Zhi Li · Xueying Zheng · Shitong Yu · Xiaojie Zhang · Yibo Fan · Xiujuan Qu · Yunpeng Liu · Xiaofang Che
Frontiers in oncology · 2019 doi:10.3389/fonc.2019.01243
Paper
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Experiment
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Data
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Analysis
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Execution
absent
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Complete file
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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.", "claims": [{"id": "claim-method", "statement": "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.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31803620", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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