ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A and B breast cancer

Abstract

Chondroitin sulfate synthase 2 (CHPF) is characterized as an oncogenic and poor prognosis-related gene in breast cancer. However, this gene has alternative splicing products encoding proteins of different lengths. Breast cancer is a group of heterogeneous tumors with distinct clinical and genomic characteristics. In this study, we explored the expression profile and prognostic value of the two transcripts of CHPF using data from The Cancer Genome Atlas (TCGA)-BRCA. The functional regulation of the two transcripts was also studied in MCF-7 and BT-474 cells. Among the two transcripts of CHPF, ENST00000535926 expression was significantly upregulated in the tumor samples and was the dominant isoform. ENST00000535926, but not ENST00000243776 upregulation, was associated with significantly worse progression-free survival (PFS) and disease-specific survival (DSS) in luminal A/B cases. However, no significant association was observed in PFS or DSS in other Prediction Analysis of Microarray 50 (PAM50) subgroups. CHPF isoform 2 protein (encoded by ENST00000535926) significantly elevated the expression of P3H1 and RCN3 at the mRNA and protein levels in MCF-7 and BT-474 cells. The effect of ENST00000535926 was significantly stronger than ENST00000243776 in promoting tumor cell colony formation. The expression of P3H1 and RCN3 was negatively correlated with CD8+ T cell infiltration but was positively correlated with cancer-associated fibroblast infiltration in luminal A/B tumors. In summary, this study revealed that ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A/B breast cancer.