CD44 is a prognostic biomarker and correlated with immune infiltrates in gastric cancer

Abstract

Objective Gastric carcinoma is the most common malignant tumour of the human digestive system worldwide. CD44 serves as a marker for several tumour stem cells, including gastric cancer. However, the prognostic value of CD44 and its correlation with immune infiltration in gastric cancer remain unclear. Methods The relative expression level of CD44 RNA in gastric cancer was analysed in the TCGA and GEPIA2 databases and validated in the GEO database. Differences in CD44 between gastric cancer cell lines and normal cells were detected by real-time PCR, and the HPA database was used to analyse the differential expression of CD44 protein in gastric cancer and normal tissues. The effect of CD44 on the proliferation and migration of gastric cancer cells was detected by CCK8 and transwell assays. UALCAN was used to analyse the relationship between CD44 expression and clinical parameters, and the Kaplan‒Meier Plotter was used to evaluate the prognostic value, including overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS). The CD44 gene and protein interaction network was constructed by using the Linked Omics, GeneMANIA, STRING and DisGeNET databases. GO and KEGG analyses and GSEA of CD44 were performed by using R language. The correlation between CD44 and immune infiltration was explored by using the TIMER, CIBERSORT and GEPIA databases. Results CD44 is highly expressed in gastric cancer compared with normal tissues. Inhibition of proliferation and migration of gastric cancer cells after CD44 knockdown was observed. The UALCAN database showed that CD44 was independent of sex in gastric cancer but correlated with cancer stage and lymph node metastasis. Kaplan‒Meier Plotter online analysis showed that OS, PFS and PPS were prolonged in the CD44 low-expression group. GO and KEGG analyses and GSEA results showed that CD44 was mainly located in the endoplasmic reticulum and the extracellular matrix containing collagen, which was mainly involved in protein digestion and absorption. TIMER, CIBERSORT and GEPIA showed that CD44 was associated with infiltrating immune cells and thereby affected survival prognosis. Conclusion CD44 is highly expressed in gastric cancer and is an independent prognostic factor associated with immune invasion, which can be used as a candidate prognostic biomarker to determine the prognosis associated with gastric immune invasion.

PHD finger protein 10 promotes cell proliferation by regulating CD44 transcription in gastric cancer

“…Among them, we found that CD44 might be a good candidate since the latter was a well-known target of the SWI/SNF complex [ 28 ] and a proven marker of gastric cancer stem cells (GCSCs) [ 29 , 30 ], associated with proliferation of gastric epithelial cells [ 31 ]. Furthermore, CD44 was also known to be closely related to cell invasiveness and poor prognosis of GC [ 32 ]. Thus, using ChIP assay, we explored that PHF10, one catalytic subunit of the SWI/SNF complex (BRG1) and two core regulatory subunits (BAF155 and SNF5) could all bind to promoter of CD44 gene in two different cell lines of GC (SGC7901 and MKN28).…”

RUNX1/CD44 axis regulates the proliferation, migration, and immunotherapy of gliomas: A single-cell sequencing analysis

“…In line with our findings, GDF15 promotes the immune escape of ovarian cancer by targeting CD44 in dendritic cells ( 46 ). CD44 correlates with immune infiltrates in gastric cancer ( 47 ). Besides, IL18 increases the immune escape of gastric cancer by downregulating CD70 and maintaining CD44 ( 48 ).…”

Zyxin inhibits the epithelial–mesenchymal transition process in gastric cancer by upregulating SIRT1

“…The conversion of CD44s to CD44v promotes tumorigenesis 26 . High CD44 expression was observed in gastric cancer, and its expression correlates with immune cell infiltration 27 . Zyxin is also involved in immune cell infiltration in ulcerative colitis 28 .…”