Characterization and clinical relevance of PDGFRA pathway copy number variation gains across human cancers

Abstract

We investigated the copy number variation (CNV) of PDGFRA pathway across all common cancer types as well as its clinical relevance. This study included a total of 10,678 patients with pan-cancerous species involving 33 types of cancers and patient information was obtained from The Cancer Genome Atlas. According to the PDGFRA pathway CNV, all samples were divided into copy number gain (CN gain) group and No CN gain group. The analysis of loss of heterozygosity (LOH) fraction, CNV burden, tumor mutation burden (TMB), and the number of immunogenic mutations were performed, as well as the correlation analysis of PDGFRA pathway CN gain with tumor-related signaling pathways and tumor-infiltrating immune cell subpopulations. The results showed that CN gain of PDGFRA pathway in the cancer patients was associated with significantly shorter overall survival. The CN gain of PDGFRA pathway was identified as a prognostic risk factor for some tumors. CN gain was accompanied by an altered percentage of LOH, CNV burden, TMB, the number of immunogenic mutations were increased and tumor-infiltrating immune cell subpopulations were less. While certain tumor-related signaling pathways, such as hypoxia, cell cycle, DNA repair, and epithelial-mesenchymal transition were more enriched in the CN gain group, quiescence, and inflammation pathways were more enriched in the No CN gain group. In conclusion, PDGFRA pathway CNV gain may be a poor prognostic factor in cancer patients.

KLF4 inhibited the senescence-associated secretory phenotype in ox-LDL-treated endothelial cells via PDGFRA/NAMPT/mitochondrial ROS

“…Furthermore, increased PDGFRA expression may be due to the direct transcriptional promotion of PDGFRA by KLF4. This regulatory network would be consistent with the notion that "PDGF-independent PDGFR activation may play more key role in much more story" [36] and the phenomenon wherein "PDGFRA expression increased together with KLF4 expression in stem cells" [37].…”

Inflammatory Fibroid Polyps and Platelet-Derived Growth Factor Receptor Mutation Analysis

“…However, the most fundamental criterion is histopathology.Therefore, when we encounter the morphological appearance described above, inflammatory fibroid polyp should be considered. PDGFR mutation has been reported in different tumors (such as epithelial, mesenchymal) (12). The mutation seen in the inflammatory myofibroblastic tumor, which is in the differential diagnosis morphologically, has been identified as PDGFRB (13).…”