Evaluation of K-ras and p53 expression in pancreatic adenocarcinoma using the cancer genome atlas

Abstract

Genetic alterations in K-ras and p53 are thought to be critical in pancreatic cancer development and progression. However, K-ras and p53 expression in pancreatic adenocarcinoma have not been systematically examined in The Cancer Genome Atlas (TCGA) Data Portal. Information regarding K-ras and p53 alterations, mRNA expression data, and protein/protein phosphorylation abundance was retrieved from The Cancer Genome Atlas (TCGA) databases, and analyses were performed by the cBioPortal for Cancer Genomics. The mutual exclusivity analysis showed that events in K-ras and p53 were likely to co-occur in pancreatic adenocarcinoma (Log odds ratio = 1.599, P = 0.006). The graphical summary of the mutations showed that there were hotspots for protein activation. In the network analysis, no solid association between K-ras and p53 was observed in pancreatic adenocarcinoma. In the survival analysis, neither K-ras nor p53 were associated with both survival events. As in the data mining study in the TCGA databases, our study provides a new perspective to understand the genetic features of K-ras and p53 in pancreatic adenocarcinoma.

Genetic mapping of pancreatic cancer by targeted next-generation sequencing in a cohort of patients managed with nab-paclitaxel-based chemotherapy or agents targeting the EGFR axis: a retrospective analysis of the Hellenic Cooperative Oncology Group (HeCOG)

“…Moreover, the co-expression of these mutations has been investigated and data support that they can co-occur in pancreatic cancer but are found in different neoplasia pathways. More recent research in animal models suggests that alterations in both KRAS and TP53 can induce the onset of PACs indicating a possible pathogenetic role of this co-occurrence 18…”

Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells

“… 49 Furthermore, these KRAS mutations induce p53 mutation and suppress p53 expression for cancer maintenance. 20 , 50 In the case of pancreatic cancer cells, MIA PaCa-2 has KRAS mutation, which induces apoptosis through the GADD45a and p38 MAPK pathway. In contrast, BxPC-3 cells carry wild type Ras which suppresses GADD45a expression.…”

Molecular Mechanisms and Potential Therapeutic Reversal of Pancreatic Cancer-Induced Immune Evasion

“…The tumor suppressor TP53 is a key regulator of cell cycle progression. The mutation of TP53 is found in approximately up to 70% of PDACs [ 19 ]. In the presence of multiple stressors that will trigger uncontrolled cell proliferation, it safeguards against cell division by inducing cell death or senescence [ 20 ].…”