PLOS ONE (2022). DOI: 10.1371/journal.pone.0273520″ width=”800″ height=”530″/>

Differential low-level Mic60 gene expression in cancer. credit: PLANE ONE (2022). DOI: 10.1371/journal.pone.0273520

Mitochondria are the key energy component of the human cell, which plays an important role in the metabolism of cancer cells. In a research paper published in PLANE ONEDario C. Altieri, MD, president and chief executive officer, director of the Ellen and Ronald Kaplan Cancer Center and Robert and Penny Fox Wistar Institute Professor Emeritus, along with national and international collaborators, identifies a specific gene signature that indicates mitochondrial reprogramming in tumors , which correlates with poor patient outcome.

“To our knowledge, this is the first case where a gene signature of mitochondrial dysfunction has been associated with aggressive cancer subtypes, treatment resistance and, unfortunately, poor patient survival. Although our work has focused on the mitochondrial protein Mic60 in this reaction, we know that non-functional mitochondria are usually created during tumor growthsuggesting that this is a common feature in cancer,” says Altieri.

This article was created based on previous studies of the role of the Mic60 protein in tumor cell proliferation, motility, and metastasis. Mic60, also called mitofilin or mitochondrial inner membrane protein (IMMT), is a key protein essential for mitochondrial structure and thus affects mitochondrial function and tumor metabolism.

Andrew Kasenkow, Ph.D., first author of the paper, associate professor in the Wistar Program on Gene Expression and Regulation, and director of the Institute for Bioinformatics, says: “After initial findings of strong association of Mic60 at low levels in cancer tissues, we wondered whether we could identify a small a panel of Mic60 downstream genes with specific functions, and whether the signature of the Mic60-low gene panel has clinical relevance, i.e., is it associated with clinical data such as survival, cancer subtypes, response to treatment, etc.—and we did “.

Armed with this knowledge, the team, along with collaborators from Canada, Italy and the United States, analyzed tumor cells from three independent cohorts of patients with pancreatic ductal adenocarcinoma (PDAC). They showed that the Mic60-low 11-gene signature is associated with aggressive disease, local inflammation, treatment failure, and shortened survival — ultimately demonstrating the protein’s clinical relevance. Therefore, the Mic60-low gene signature can be used as a simple tool or biomarker for evaluation cancer risk for PDAC and potentially other types of cancer, including glioblastoma.

“Gene signatures can be used to gain insight into specific qualities of a tumor,” Kasenkov explains. “If it is extensively developed, tested and validated [Mic60-low gene signature] may be a potential simple point-of-care molecular tool pancreatic cancer prognosis or patient risk stratification and prediction of response to treatment.”

“Although the widespread application of this new Mic60-low gene signature certainly awaits further validation in a larger group of patients, we hope that this simple, easy-to-implement molecular tool will be useful in the clinic to stratify patients with more the risk of severe and progressive disease. ” – says Altieri.

As for future directions, Kasenkov suggests that studying larger datasets with extensive clinical information, not limited to pancreatic cancer but also including other malignancies, may help demonstrate the applicability of the 11-gene Mic60-low signature in cancer risk assessment.

Researchers describe an important component in the body’s energy supply mechanism

Additional information:
Andrew V. Kasenkow et al., Mitochondrial Fitness and Cancer Risk, PLANE ONE (2022). DOI: 10.1371/journal.pone.0273520

Citation: Scientists Identify Link Between Mitochondria and Pancreatic Cancer Risk (2022, October 12) Retrieved October 12, 2022, from .html

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