Five EMT‐related genes signature predicts overall survival and immune environment in microsatellite instability‐high gastric cancer

Abstract

Background Microsatellite instability‐high (MSI‐H) subgroup of gastric cancer (GC) is characterized by a high tumor mutational burden, increased lymphocytic infiltration, and enhanced inflammatory cytokines. GC patients with MSI‐H status have a good response to immune checkpoint blockade management. However, heterogeneity within the subtype and the underlying mechanisms of shaping tumor microenvironments remain poorly understood. Methods RNA expression levels and clinical parameters of GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The data were analyzed using single‐sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression. In addition, multiplex immunohistochemistry (mIHC) was used in our clinical cohort for the tumor microenvironment study. Results By ssGSEA and survival analysis, the EMT signaling pathway was identified as a representative pathway, which can stratify the patients with MSI‐H GC with significant survival predictive power. Then, a novel representative EMT‐related five‐gene signature (namely CALU, PCOLCE2, PLOD2, SGCD, and THBS2) was established from EMT signaling gene set, which sensitivity and specificity were further validated in the independent GEO database (GSE62254) cohort for disease outcome prediction. Based on public single‐cell data and in situ immunohistochemistry, we found that most of these five genes were abundantly expressed in cancer‐associated fibroblasts. Furthermore, patients with high or low risk divided by this five‐gene signature exhibited a strong correlation of the distinct patterns of tumor immune microenvironment. By mIHC staining of sections from 30 patients with MSI‐H status, we showed that the patients with better prognoses had the increased infiltration of CD8+ cells in the primary tumoral tissue. Conclusion Our study developed a simple five‐gene signature for stratifying MSI‐H GC patients with survival predictive power.

LncRNA THUMPD3-AS1 promotes invasion and EMT in gastric cancer by regulating the miR-1297/BCAT1 pathway

“… 23 , 24 Therefore, in-depth exploration of the invasion and metastasis mechanism of gastric cancer and identification of key molecules in it have important potential application value in gastric cancer research. 25 , 26 , 27 As a key regulatory factor of cancer, lncRNAs regulate the expression of cancer-related genes at different levels. Convincing evidence indicates that lncRNAs play an important role in the pathogenesis of GC and have great value for GC diagnosis and treatment.…”

Characterization and verification of CAF-relevant prognostic gene signature to aid therapy in bladder cancer

“…A study has shown the involvement of BMP1 in gastric and non-small cell lung cancer metastases [ 39 ]. Furthermore, PCOLCE plays a key role in promoting lung metastasis of osteosarcoma [ 40 ] and participates in EMT [ 41 ]. A recent study has shown that PCOLCE2 stimulates the production of reactive oxygen species in neutrophils [ 42 ].…”

The crosstalk between anoikis and epithelial-mesenchymal transition and their synergistic roles in predicting prognosis in colon adenocarcinoma

“…Procollagen C-endopeptidase enhancer 2 (PCOLCE2) refers to a collagen-binding protein that binds to the C-terminal pro-peptide of types I and II procollagens and could enhance the cleavage of the pro-peptide by BMP1 ( 42 ). PCOLCE2 can be considered as an EMT-linked gene for anticipating the prognosis of gastric cancer patients ( 43 , 44 ) and the metastasis ability of COAD ( 45 ). However, none of the studies determined the role of PCOLCE2 in anoikis.…”