Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China.
Pathol Res Pract. 2020 Dec;216(12):153244. doi: 10.1016/j.prp.2020.153244. Epub 2020 Oct 9.
To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), suggesting that comprehensive understanding of genomic changes turns out to be an urgent need to break through the calm of currently known therapies of NPC.
Whole exome sequencing (WES) was performed for 14 NPC patients, including 6 NPC-IIA cases, 8 NPC-IIB cases. The cancer chip expression data named GSE12452 was downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) of each subtype were obtained using the Lima R package. Then gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) network and Gene Set Enrichment Analysis (GSEA) were performed. Finally 7 potentially subtype relevant genes (PSRGs) were obtained.
In total, 37 clinically relevant mutations (CRMs) were obtained from WES. The 2 NPC subtypes exhibited different mutational landscapes, indicating that different NPC subtypes harbor different CRMs. Notably, we discovered that mutations of CCND1 and FGF family appeared simultaneously in 3 NPC-IIB cases, but 0 in NPC-IIA. In addition, 1395 DEGs were identified from GSE12452. PI3K-Akt signaling pathway showed significant enrichment in both the pathway distribution of CRMs and KEGG analysis of DEGs, suggesting that it is a key pathway in the development of NPC. Through PPI analysis of genes involved in the PI3K-Akt pathways and expression significance analysis of DEGs co-expressed by the 2 subtypes, 54 genes finally were screened for expression significance analysis. The GSEA analysis between patients with high and low expression of 11 candidate genes were performed. As a result, 7 PSRGs were selected, including COL4A1, ASB9, RDH10, TNFRSF21, BACE2, EVA1C and LHX2.
These results indicate that different NPC subtypes have different genetic changes, suggesting that they may be potential targets for the diagnosis and treatment of NPC, and ultimately point to new strategies for intelligence.
迄今为止，尚无针对鼻咽癌（NPC）的靶向治疗药物获批，这表明全面了解基因组变化对于突破目前 NPC 已知疗法的瓶颈显得尤为迫切。
对 14 名 NPC 患者进行全外显子组测序（WES），包括 6 例 NPC-IIA 病例和 8 例 NPC-IIB 病例。从基因表达综合数据库（GEO）下载名为 GSE12452 的癌症芯片表达数据，使用 Lima R 包获得每个亚型的差异表达基因（DEGs）。然后进行基因本体（GO）功能富集和京都基因与基因组百科全书（KEGG）通路分析。进行蛋白质-蛋白质相互作用（PPI）网络和基因集富集分析（GSEA）。最后得到 7 个潜在的亚型相关基因（PSRGs）。
WES 共获得 37 个临床相关突变（CRMs）。这 2 个 NPC 亚型表现出不同的突变景观，表明不同的 NPC 亚型具有不同的 CRMs。值得注意的是，我们发现 CCND1 和 FGF 家族的突变同时出现在 3 例 NPC-IIB 病例中，但 NPC-IIA 中却没有。此外，从 GSE12452 中鉴定出 1395 个 DEGs。PI3K-Akt 信号通路在 CRMs 的通路分布和 DEGs 的 KEGG 分析中均显示出显著富集，表明其是 NPC 发展的关键通路。通过对 PI3K-Akt 通路中基因的 PPI 分析以及 2 个亚型共表达的 DEGs 的表达意义分析，最终筛选出 54 个基因进行表达意义分析。对 11 个候选基因高表达和低表达患者进行 GSEA 分析。结果筛选出 7 个 PSRGs，包括 COL4A1、ASB9、RDH10、TNFRSF21、BACE2、EVA1C 和 LHX2。
这些结果表明不同的 NPC 亚型具有不同的遗传变化，提示它们可能是 NPC 诊断和治疗的潜在靶点，最终为智能治疗提供新策略。
