Clinical value of bone morphogenetic protein antagonist GREM1 as an immuno-active indicator in tumor microenvironment of gastric cancer
Objective:To screen prognostic genes as indicators for predicting immunoactive in tumor microenvironment(TME)of gastric cancer(GC).Methods:Paraffin tissue specimens and corresponding paracancer tissues were collected from 55 patients with GC.Total 976 GC transcriptome RNA-Seqs and clinical datasets were obtained from TCGA and GEO databases.Infiltra-tion status of immune cells and Immune/Stormal scores were calculated using the ESTIMATE and CIBERSORT algorithm.R package"limma"was performed to selected differentially expressed genes(DEGs).Univariate Cox regression analysis was used to determine prognostic factors of DEGs.qRT-PCR was demonstrated to detect mRNA expression of the hub genes.Potential biological functions of GREM1 were investigated by GSEA.Correlations of GREM1 with immune signature molecules and drug susceptibility were investigated by TISIDB and CellMiner database.Results:Immune Score was positively correlated with improved outcomes of GC patients.A total of 40 shared TME-related DEGs were selected in the high and low groups of Immune Score and Stromal Score.Four survival-related DEGs were obtained by Cox analysis,which were GREM1,SFRP2,CYP1B1 and MGP.By comparing the difference of gene expres-sion in tumor and adjacent tissues and the degree of affinity with immune microenvironment,it was found that GREM1 was most likely to play a role in immune remodeling in TME;expression of GREM1 was positively correlated with clinicopathological features(TNM),while negatively correlated with survival time of GC patients.GSEA results showed that GREM1 high-expression group were mainly enriched in immune-related active genomes.Besides,GREM1 expression was positively correlated to M2 macrophages,while negatively correlated to CD8+T cells.GREM1 was also positively associated with immunosuppressor TGF-β1,immunopotentiator ENT-PD1,chemokine CCL14 as well as receptor CCR2.Moreover,GC patients with high expression of GREM1 might more sensitive to drug Vismodegib therapy.Conclusion:GREM1 can regard as an immunosuppressive clinical indicator in TME of GC.
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