Role of protein in KRAS mutation in pancreatic cancer explored
Pancreatic cancer is a devastating disease that is often associated with mutation of a gene called KRAS. Improvement of pancreatic cancer therapy requires sensitive early detection techniques and a better understanding of the biology involved in the formation or presence new, abnormal pancreatic tissue (pancreatic neoplasia). As described in Oncotarget, Volume 8, Issue 54, researchers studied the role of the antioxidant protein called Prdx1 in pancreatic abnormal tissue growth and cancer by determining how it regulates the gene KRAS.
In general, when the KRAS gene mutates, it can cause normal cells to become cancerous. Likewise this KRAS mutation can activate a protein called Nrf2 which controls how certain genes are expressed.
It is also known that the antioxidant protein Prdx1 is elevated in pancreatic cancer patient tissue and serum. Prdx1 is a member of a system of antioxidant proteins (Thioredoxin-associated, or Txn, system) which is regulated by proteins called Nrf2 and Nrf1, which play a role in activating metabolic genes responsible for regulating cellular growth.
Researchers evaluated the expression of Prdx1 in pancreatic abnormal tissue growth. In pancreatic cancer patients, researchers found elevated levels of the protein Prdx1 in the amino acid sequences that transport proteins into the cell nucleus (nuclear localization). They studied the role of the Prdx1 protein in context of the Txn system, and role in the growth of pancreatic abnormal tissue and cancer. Researchers found that elevated levels of Prdx1 in the cell nucleus significantly correlated with better patient survival.
What role does Prdx1 protein play in pancreatic cancer?
They found that overall Prdx1 expression was elevated in tumor tissue as compared to adjacent normal tissue in a pancreatic cancer patient tumor sample group. Researchers then examined the correlation between Prdx1 transport into the cell nucleus, overall survival, and other parameters in a separate patient tumor samples group. They found that there was a highly significant positive correlation between high nuclear Prdx1 expression and longer survival of patients.
The median survival of patients with low nuclear Prdx1 expression was 20.4 months and the median survival of patients with high levels of nuclear Prdx1 was 43.92 months. Interestingly, there was also a near significant association between low nuclear Prdx1 expression and positive lymph node involvement. There was no significant correlation between nuclear Prdx1 expression and age, gender, and extent to which the tumors had spread or size of the tumor, among other factors. These data suggests that Prdx1 expression and localization is associated with changes in patient survival in pancreatic cancer.