USA Health researchers identify potential biomarker for early pancreatic cancer diagnosis
MOBILE, Ala. (WKRG) — Cancer researchers with the USA Health Mitchell Cancer Institute and the University of South Alabama have identified a potential biomarker for early diagnosis and prognosis of pancreatic cancer.
Cancer researchers identified the TOMM22 protein and could also be a useful therapeutic target.
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“Pancreatic cancer is a very aggressive disease that spreads rapidly, and its early diagnosis is very challenging,” Santanu Dasgupta, Ph.D., an assistant professor of pathology at the Frederick P. Whiddon College of Medicine and principal investigator of the project, said. “Moreover, due to the lack of curative treatments at advanced stages, the survival of patients is short. Thus, we urgently need to find ways to detect pancreatic cancer early along with a new line of treatment.”
Their research was published in Molecular Cancer Research, a journal featuring articles describing novel basic cancer research discoveries.
Researchers explain that mitochondria are small parts of the cell that “make most of the energy for the cell.” According to Dasgupta, cancer cells use mitochondria to fulfill their energy demands and avoid death. In the research, Dasgupta and others found that the majority of proteins harbored in the mitochondria are imported through a system that operates through proteins called translocases of the outer mitochondrial membrane (TOMM).
“We discovered that TOMM22, the central outer mitochondrial membrane translocase, is abundantly expressed in patients diagnosed with pancreatic cancer,” Dasgupta said. “When we engineered pancreatic cancer cells to express high amounts of TOMM22, they became more aggressive, indicating that TOMM22 promotes cancer growth and spread. We observed that TOMM22 abundance increased mitochondrial energy production, thereby supporting the aggressive growth of the pancreatic cancer cells.”
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The research showed pancreatic cancer cells became much less aggressive when the researchers blocked the TOMM22 function.
“We discovered that when the TOMM22 gate is locked, many essential proteins associated with energy generation and management of stress could not enter the mitochondria of the cancer cells,” Dasgupta said. “As a result, cancer cells experienced stress and became helpless.”
The lab is developing suitable drugs to block TOMM22 as it could be a feasible target to overcome the inadequacy of pancreatic cancer therapy, Dasgupta said.
The release said scientists saw an increase in the expression of TOMM22 protein from pre-invasive to invasive pancreatic lesions, and it was barely detectable in normal cells. The increase in TOMM22 expression was associated with the worst prognosis of patients with pancreatic cancer.
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Dasgupta said the increase of the TOMM22 expression in pancreatic cancer patients was a better prognostic indicator than a tumor grade.
“These findings are very encouraging and necessitate analysis of a large number of patients to establish TOMM22 as a useful biomarker for early diagnosis and prognosis,” he added.
The release noted that this is the first study to show the mitochondrial protein import system’s role in promoting pancreatic cancer.
“We have just begun to understand how cancer cells hijack this unique import machinery to achieve their benefits,” Dasgupta said. “A comprehensive characterization of this import pathway in various other cancers may lead to the development of better disease management strategies to ultimately improve the overall survival of cancer patients.”
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Mary O. Haastrup, M.D., Ph.D., who earned her doctoral degree in basic medical sciences from the Whiddon College of Medicine in 2023, is the lead author of the article. Additional authors from the Mitchell Cancer Institute and the University of South Alabama include Kunwar Somesh Vikramdeo, Ph.D.; Shashi Anand, Ph.D.; Mohammad Aslam Khan, Ph.D.; James Elliott Carter, M.D.; Seema Singh, Ph.D.; and Ajay Pratap Singh, Ph.D.
You can read the Molecular Cancer Research Abstract, here.
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