The Mic60 low gene signature could be a simple tool to estimate the risk of pancreatic cancer

The mitochondria are an important energy-producing component of the human cell that plays an important role in cancer cell metabolism. In a research paper published in PLUS ONEDario C. Altieri, MD, President and Chief Executive Officer, Director of the Ellen and Ronald Caplan Cancer Center and the Robert and Penny Fox Distinguished Professor at the Wistar Institute, along with national and international collaborators, distinguish a specific gene signature indicative of mitochondrial reprogramming in tumors, which correlates with a poor patient outcome.

To the best of our knowledge, this is the first time that a mitochondrial dysfunction gene signature has been associated with aggressive cancer subtypes, treatment resistance and, unfortunately, low patient survival rates. Although our work has focused on the mitochondrial protein Microphone60 In this answer we know that dysfunctional mitochondria are often generated during tumor growth, suggesting that this is a common feature in cancer.”

Dario C. Altieri, MD, President and Chief Executive Officer, Director of the Ellen and Ronald Caplan Cancer Center and Robert and Penny Fox Distinguished Professor at the Wistar Institute

This paper stems from previous research examining the role of the protein Microphone60 in tumor cell proliferation, motility and metastases. Microphone60also called mitofilin or inner membrane mitochondrial protein (IMMT), is a key protein that is essential for the structure of the mitochondria and thus has a downstream influence on mitochondrial functions and tumor metabolism.

Andrew Kossenkov, Ph.D., first author of the article, assistant professor in Wistar’s Gene Expression and Regulation program and scientific director of the institute’s bioinformatics facility, shares: “After initial evidence of the strong association of Microphone60 at low levels in cancer tissues, we were curious to see if we could identify a small group of them Microphone60 downstream genes of certain functions and possibly Microphone60-A low gene panel signature has clinical relevance – ie when linked to clinical data such as survival, cancer subtypes, response to treatment, etc. – and we have that.”

Armed with this knowledge, the team—along with collaborators from Canada, Italy, and the United States—analyzed tumor cells from three independent patient cohorts with pancreatic ductal adenocarcinoma (PDAC). They showed that an 11 gene Microphone60-low signature is associated with aggressive disease, local inflammation, treatment failure and shortened survival – ultimately demonstrating the clinical relevance of protein. therefore, the Microphone60-low gene signature can be used as a simple tool or biomarker to estimate cancer risk for PDAC and potentially other cancers including glioblastoma.

“On the basis of gene signatures, knowledge about certain tumor properties can be gained,” explains Kossenkov. “When extensively developed, tested and validated, this is [Mic60-low gene signature] may be a potential simple molecular point-of-service tool for pancreatic cancer prognosis or patient risk stratification and prediction of treatment response.”

“While the wide applicability of this new Microphone60-low gene signature certainly awaits further confirmation in larger patient populations, we hope that this simple, easy-to-implement molecular tool will be useful in the clinic to stratify patients at higher risk for severe and progressive disease,” Altieri concludes out.

Regarding future directions, Kossenkov suggests that examining broader datasets with rich clinical information not limited to pancreatic cancer but also other malignancies can help demonstrate the applicability of the 11 gene Microphone60-low signature in cancer risk estimation.