Department of Oncology, The First Affiliated Hospital of Harbin Medical University, No.23 Post Street Nangang District, Harbin, 150001, China.
Genecast Biotechnology Co., Ltd, Wuxi, 214104, China.
Mol Genet Genomics. 2022 Mar;297(2):561-571. doi: 10.1007/s00438-022-01860-y. Epub 2022 Feb 25.
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.
我们研究了 PDGFRA 通路在所有常见癌症类型中的拷贝数变异 (CNV) 及其临床相关性。这项研究共纳入了 10678 名患有泛癌种的患者,涉及 33 种癌症,患者信息来自癌症基因组图谱。根据 PDGFRA 通路 CNV,所有样本被分为拷贝数增益 (CN 增益) 组和无 CN 增益组。分析杂合性缺失 (LOH) 分数、CNV 负担、肿瘤突变负担 (TMB) 和免疫原性突变数量,并对 PDGFRA 通路 CN 增益与肿瘤相关信号通路和肿瘤浸润免疫细胞亚群进行相关性分析。结果表明,癌症患者 PDGFRA 通路的 CN 增益与总生存期显著缩短相关。PDGFRA 通路的 CN 增益被确定为某些肿瘤的预后危险因素。CN 增益伴随着 LOH、CNV 负担、TMB 的百分比发生改变,免疫原性突变数量增加,肿瘤浸润免疫细胞亚群减少。虽然某些肿瘤相关信号通路,如缺氧、细胞周期、DNA 修复和上皮-间充质转化,在 CN 增益组中更为丰富,而静止和炎症通路在无 CN 增益组中更为丰富。总之,PDGFRA 通路 CNV 增益可能是癌症患者的不良预后因素。