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.
Background Osteosarcoma (OS) is a malignant bone tumour of mesenchymal origin. These tumours are characterised by rich vascularisation, therefore promoting rapid proliferation and facilitating metastasis. CD44 has been reported to be involved in OS, but its role and molecular mechanisms in the pathogenesis of the disease are not fully determined. Methods In this study, we investigated the antitumor effect of CD44 on the development of OS and further explored the molecular mechanisms. The expression of CD44, cathepsin S and MMP-9 was detected by Western blot (WB) and reverse transcription-polymerase chain reaction (RT-qPCR) in different cell lines (MG63, U2OS OS and hFOB 1.19). To elucidate the role of CD44 in OS, MG63 and U2OS cells were treated with small interference RNA (siRNA) to knock down CD44, and the knockdown efficiency was validated with GFP and RT-qPCR. Furthermore, cell proliferation was assayed using Cell Counting Kit‑8 (CCK-8) and colony formation assays, and cell migration and invasion were assayed by transwell and wound-healing assays. Results We found that CD44 expression in the MG63 and U2OS OS cell lines was markedly increased compared to that of the human osteoblast hFOB 1.19 cell line. Knockdown of CD44 inhibited proliferation, migration and invasion of MG63 and U2OS cells. Cathepsin S expression in the MG63 and U2OS OS cell lines was increased compared to that of the human osteoblast hFOB 1.19 cell line. When CD44 was knocked down, its expression level went down. Conclusion Taken together, our data reinforced the evidence that CD44 knockdown inhibited cell proliferation, migration and invasion of OS cells accompanied by altered expression of cathepsin S. These findings offer new clues for OS development and progression, suggesting CD44 as a potential therapeutic target for OS.
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