October 13, 2022 -- Wistar Institute researchers have found a specific gene signature indicative of mitochondrial reprogramming in tumors that correlates with poor patient outcomes. It’s the first time ever that mitochondrial dysfunction has been linked to aggressive cancer subtypes, treatment resistance, and low patient survival rates, according to the researchers.
The study focuses on Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT), which is a protein essential for the mitochondria structure and has a downstream effect on mitochondrial functions and tumor metabolism (PLOS ONE, October 12, 2022).
The paper builds on previous work and identifies a small panel of Mic60 downstream genes of specific functions. The researchers found the Mic60-low gene panel signature has clinical relevance and along with collaborators from Canada, Italy, and across the U.S., they analyzed tumor cells from three independent patient cohorts with pancreatic ductal adenocarcinoma (PDAC).
They found an 11-gene Mic60-low signature is associated with aggressive disease, local inflammation, treatment failure, and shortened survival. Based on the findings, the Mic60-low gene signature may be used as a tool or biomarker to estimate the cancer risk for PDAC and potentially other types of cancer, including glioblastoma, according to the researchers.
The broad applicability of the gene signature needs more research in larger patient populations, but even still, it could be helpful to clinicians to stratify patients at higher risk of severe and progressive disease, the researchers said. Also, future research could investigate broader datasets beyond pancreatic cancer.
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