Background: The most frequently mutated gene pairs in pancreatic adenocarcinoma (PAAD) are KRAS and TP53, and our goal is to illustrate the multiomics and molecular dynamics landscapes of KRAS/TP53 mutation and also to obtain prospective novel drugs for KRAS- and TP53-mutated PAAD patients. Moreover, we also made an attempt to discover the probable link amid KRAS and TP53 on the basis of the abovementioned multiomics data. Method: We utilized TCGA & Cancer Cell Line Encyclopedia data for the analysis of KRAS/TP53 mutation in a multiomics manner. In addition to that, we performed molecular dynamics analysis of KRAS and TP53 to produce mechanistic descriptions of particular mutations and carcinogenesis. Result: We discover that there is a significant difference in the genomics, transcriptomics, methylomics, and molecular dynamics pattern of KRAS and TP53 mutation from the matching wild type in PAAD, and the prognosis of pancreatic cancer is directly linked with a particular mutation of KRAS and protein stability. Screened drugs are potentially effective in PAAD patients. Conclusions: KRAS and TP53 prognosis of PAAD is directly associated with a specific mutation of KRAS. Irinotecan and vandetanib are prospective drugs for PAAD patients with KRAS^G12Dmutation and TP53 mutation.

中文翻译：

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伊立替康和凡德他尼为治疗伴有 TP53 和 KRAS 突变的胰腺癌患者创造了协同作用。

背景：胰腺腺癌（PAAD）中最常见的突变基因对是 KRAS 和 TP53，我们的目标是阐明 KRAS/TP53 突变的多组学和分子动力学景观，并获得针对 KRAS 和 TP53 突变的前瞻性新药PAAD 患者。此外，我们还尝试在上述多组学数据的基础上发现 KRAS 和 TP53 之间的可能联系。方法：我们利用 TCGA 和癌细胞系百科全书数据以多组学方式分析 KRAS/TP53 突变。除此之外，我们对 KRAS 和 TP53 进行了分子动力学分析，以产生特定突变和致癌作用的机制描述。结果：我们发现基因组学、转录组学、甲基组学、PAAD 中匹配的野生型 KRAS 和 TP53 突变的分子动力学模式和分子动力学模式，胰腺癌的预后与 KRAS 的特定突变和蛋白质稳定性直接相关。筛选的药物可能对 PAAD 患者有效。结论：PAAD 的 KRAS 和 TP53 预后与 KRAS 的特定突变直接相关。伊立替康和凡德他尼是 PAAD 合并 KRAS 患者的前瞻性药物^G12D突变和TP53突变。