Abstract
BackgroundRecent studies in the United States have shown that breast cancer accounts for 30% of all new cancer diagnoses in women and has become the leading cause of cancer deaths in women worldwide. Chondroitin Polymerizing Factor (CHPF), is an enzyme involved in chondroitin sulfate (CS) elongation and a novel key molecule in the poor prognosis of many cancers. However, its role in the development and progression of breast cancer remains unclear.MethodsThe transcript expression of CHPF in the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA), Gene Expression Omnibus (GEO) database was analyzed separately using the limma package of R software, and the relationship between CHPF transcriptional expression and CHPF DNA methylation was investigated in TCGA-BRCA. Kaplan-Meier curves were plotted using the Survival package to further assess the prognostic impact of CHPF DNA methylation/expression. The association between CHPF transcript expression/DNA methylation and cancer immune infiltration and immune markers was investigated using the TIMER and TISIDB databases. We also performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with the clusterProfiler package. Western blotting and RT-PCR were used to verify the protein level and mRNA level of CHPF in breast tissue and cell lines, respectively. Small interfering plasmids and lentiviral plasmids were constructed for transient and stable transfection of breast cancer cell lines MCF-7 and SUM1315, respectively, followed by proliferation-related functional assays, such as CCK8, EDU, clone formation assays; migration and invasion-related functional assays, such as wound healing assay and transwell assays. We also conducted a preliminary study of the mechanism.ResultsWe observed that CHPF was significantly upregulated in breast cancer tissues and correlated with poor prognosis. CHPF gene transcriptional expression and methylation are associated with immune infiltration immune markers. CHPF promotes proliferation, migration, invasion of the breast cancer cell lines MCF-7 and SUM1315, and is significantly enriched in pathways associated with the ECM-receptor interaction and PI3K-AKT pathway.ConclusionCHPF transcriptional expression and DNA methylation correlate with immune infiltration and immune markers. Upregulation of CHPF in breast cancer promotes malignant behavior of cancer cells and is associated with poorer survival in breast cancer, possibly through ECM-receptor interactions and the PI3K-AKT pathway.
Highlights
Breast cancer has become the second most common cause of cancer death in women worldwide [1]
After preprocessing the data from 33 tumors obtained from UCSC Xena, differential expression analysis was performed using the limma package to compare Chondroitin Polymerizing Factor (CHPF) expression in 33 tumor samples as well as the corresponding normal samples.Significant differences in CHPF gene expression were found in BLCA, BRCA, CHOL, COAD, ESCA, GBM, HNSC, KICH, KIRC, KIRP, LIHC, LUAD, LUSC, PRAD, READ, STAD, and UCEC, and the gene expression was significantly upregulated in breast cancer (Figure 1A)
Subsequent KM survival analysis was performed and the results demonstrated a poorer prognosis in the high CHPF expression group (Figure 1C), in addition, we selected the GEO dataset GSE20685 for further validation and obtained the same results as TCGA (Figure 1D)
Summary
Breast cancer has become the second most common cause of cancer death in women worldwide [1]. The emergence of prognostic predictors is expected to improve the prognosis of breast cancer patients. The search for new markers that can achieve a prognostic role has gradually tended to continue, from the RNA level to the protein level. None of these studies has achieved a revolutionary breakthrough, and there is still an urgent need for more emerging indicators. Recent studies in the United States have shown that breast cancer accounts for 30% of all new cancer diagnoses in women and has become the leading cause of cancer deaths in women worldwide. Its role in the development and progression of breast cancer remains unclear
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