Mitochondria are the primary energy production and storage site in the human cell. Moreover, mitochondria also take part in cancer cell metabolism. A recent research paper published by Dario C. Altieri 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 in PLOS ONE reported that distinguished a specific gene revealing of mitochondrial reprogramming in tumors that relates with poor patient outcome.
Altieri stated that the aggressiveness of cancer subtypes, treatment resistance, and low patient survival rates are associated with a gene signature of mitochondrial dysfunction. Researchers of this study investigated a general trait in cancer and the response of mitochondrial protein Mic60. They found that mitochondrial dysfunction usually started during tumor growth. This study result confirmed that the protein Mic60 has a role in proliferation, motility, and metastases in the tumor cell. Mic60 is also known as inner membrane mitochondrial protein (IMMT) or mitofilin. This protein is an integral part of mitochondria structure which has a downstream influence on mitochondrial functions and tumor metabolism.
Andrew Kossenkov, Ph.D., first author on the paper, assistant professor in Wistar’s Gene Expression and Regulation program, and scientific director of the Institute’s Bioinformatics Facility, shared that after genuine conclusions of the strong association of Mic60 in low levels in cancer tissues, researchers curious to find out a small panel of Mic60 downstream genes of precise purposes. They also successfully discovered that the Mic60-low gene panel signature has clinical significance in terms of the interrelation of clinical data like survival, cancer sub-types, treatment outcome, etc.
The research team collaborated with Canada, Italy, and across the United States and was focused on this understanding and analyzed tumor cells from three independent patient cohorts with pancreatic ductal adenocarcinoma (PDAC). They found that an 11-gene Mic60-low signature has a connection with the aggressive nature of the disease, local inflammation, treatment failure, and reduction of survival rate. All these consequences demonstrate the clinical relevance of protein. The Mic60 low gene signature may be used as a simple tool or biomarker to evaluate cancer risk for PDAC and other types of cancer like glioblastoma.
Kossenkov explained that gene signatures could be used to gain an understanding of precise tumor possibilities. He also expressed that extensive development, validation, and tests will make this gene a potential simple point-of-service molecular tool for pancreatic cancer prediction or identification of patient risks and estimate of treatment outcome.
Altieri also explained that the application of the new Mic60-low gene signature in a broader way certainly anticipates confirmation in larger patient populations. The research team expected that this simple, easily implementable molecular tool will be of help in the clinic to stratify patients at higher risk of severe and progressive disease.
Regarding future prospects, Kossenkov suggests that a broader investigation of datasets with widespread clinical information not restricted to pancreatic cancer, but also other malignancies can help confirm the applicability of the 11gene Mic60-low signature in assessing cancer risks.