PRKAA1 protein seen among pancreatic cancer biomarkers: Study
Protein levels correlated with prognosis, survival odds
A protein called PRKAA1 could be among potential pancreatic cancer biomarkers and a possible treatment target, a study found.
Levels of the protein were found to be elevated in pancreatic cancer tissue, where it was correlated with a poor prognosis and worse survival odds. Lab studies showed that PRKAA1 appeared to promote the ability of pancreatic cancer cells to grow and invade tissues.
PRKAA1 was likewise altered and associated with prognosis in several other cancer types.
The study, “AMP-dependent protein kinase alpha 1 predicts cancer prognosis and immunotherapy response: from pan-cancer analysis to experimental validation,” was published in the American Journal of Cancer Research.
Pancreatic cancer is an aggressive cancer affecting the pancreas, an organ important for digestion and blood sugar control. Where surgery to remove the tumor is not possible, treatment options such as chemotherapy have limited efficacy in slowing the disease and prolonging survival. The scientists noted that “new therapeutic targets are urgently required.”
Altered gene activity
PRKAA1 is one component of AMPK, an enzyme involved in regulating cellular metabolism that’s known to influence tumor development. The exact role of PRKAA1 itself in cancer is not completely established, as it’s been associated with both tumor-promoting and suppressing activities in various contexts.
The scientists in China set out to learn more about PRKAA1’s role in cancer by examining gene activity datasets from 33 different cancer types, aiming to correlate the activity of the gene encoding PRKAA1 with clinical information from the patients the samples had come from.
PRKAA1 gene activity, or expression, was altered in several tumor type. It was increased in pancreatic adenocarcinoma, the most common type of pancreatic cancer.
High PRKAA1 expression was linked to worse survival and a poor prognosis in a number of cancers, including pancreatic adenocarcinoma.
The gene also appeared to interact with components of the immune system and genes encoding important immune proteins called checkpoint proteins in many tumor types.
“PRKAA1 exhibited a remarkable correlation with both immune cell infiltration and immune checkpoint genes, suggesting its potential as a target for tumor immunotherapy,” the researchers wrote.
The immune system has innate cancer-fighting abilities, but the tumor environment has mechanisms to avoid it. Immunotherapies are a class of treatments that help boost the immune system’s ability to kill cancer cells. There are some that are used for pancreatic cancer.
Other cancer biomarkers
Expression of PRKAA1 also correlated with other biomarkers believed to predict the efficacy of immunotherapy in a handful of the cancer types examined.
To further explore the role of PRKAA1 in pancreatic cancer, the team examined cancerous and noncancerous pancreatic tissue from people who’d undergone pancreatic cancer surgery.
PRKAA1 levels were significantly increased in the pancreatic cancer tissue relative to healthy tissue. Its levels correlated with patients’ ages as well as the size and spread of their tumors.
Ultimately, PRKAA1 expression was found to be a significant and independent predictor of prognosis in pancreatic cancer. Patients with high PRKAA1 expression also had worse odds of survival than those with lower expression.
In cell culture studies, elevations in PRKAA1 led to an increased ability for pancreatic cancer cells to grow and invade healthy cells, whereas reduced PRKAA1 expression suppressed their ability to do so.
Higher expression of PRKAA1 appeared to promote activation of the P13K/ATK signaling pathway, which is known to contribute to tumor development and progression in a variety of cancers.
“These results suggest that PRKAA1 can promote the biological progression of PC [pancreatic cancer],” the researchers wrote, noting that as such, “ PRKAA1 is a potentially useful therapeutic target for PC.”
In future studies, the team plans to further explore the mechanisms by which PRKAA1 acts in pancreatic cancer, including the role of P13K/ATK.
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