Scientists identify link between mitochondria and risk of pancreatic cancer

Mitochondria are an essential component of energy production in the human cell which plays an important role in the metabolism of cancer cells. In a research article published in PLUS ONEDario C. Altieri, MD, President and CEO, Director of the Ellen and Ronald Kaplan Cancer Center, and Distinguished Professor Robert and Benny Fox at the Wistar Institute, along with national and international collaborators, characterize a specific genetic signature indicating mitochondrial reprogramming in tumors that correlates with poor patient outcome. .

“To our knowledge, this is the first time that a genetic signature of mitochondrial dysfunction has been linked to aggressive subtypes of cancer, treatment resistance and, unfortunately, poor patient survival rates. Although our work focused on the mitochondrial protein small 60 In this response, we know that dysfunctional mitochondria are typically generated during tumor growth, which indicates that this is a general feature of cancer,” says Altieri.

This article is based on previous research on the role of protein small 60 in cancer cell proliferation, motility and spread. small 60Also called mytofilin or inner mitochondrial membrane protein (IMMT), it is an essential protein essential for mitochondrial structure and thus has a downstream effect on mitochondrial function and tumor metabolism.

Andrew Kosenkov, PhD, first author of the paper, assistant professor in the Wistar Program for Gene Expression and Regulation and Scientific Director of the Institute’s Bioinformatics Facility, shares, “Following original findings about the strong association between small 60 At low levels in cancerous tissue, we were curious to be able to identify a small panel of small 60 Downstream genes for specific functions and whether small 60The low gene panel signature is clinically relevant – that is, if it is associated with clinical data such as survival, cancer subtypes, response to treatment, etc. – And we did it.”

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Armed with this knowledge, the team — with collaborators from Canada, Italy and the United States — analyzed tumor cells from three independent groups of patients with pancreatic ductal adenocarcinoma (PDAC). They showed that gene 11 small 60The weak signature is associated with aggressive disease, localized inflammation, treatment failure and shorter survival – ultimately indicating the clinical significance of the proteins. Therefore, the small 60The weak genetic signature can be used as a simple tool or biomarker to estimate cancer risk in PDAC and other types of cancer, including glioblastoma.

“Genetic signatures can be used to better understand specific characteristics of a tumor,” Kosenkov says. “If developed, tested and validated on a large scale, this [Mic60-low gene signature] It could be a potential point-of-care molecular tool for pancreatic cancer prediction or patient risk stratification and treatment response prediction.

Despite the wide application of this new small 60– Weak DNA fingerprinting certainly awaits further confirmation in larger numbers of patients, and we hope that this simple and easy-to-implement molecular tool will be useful in the clinic for stratifying patients at higher risk of serious and exacerbating disease,” Thierry details.

Regarding future directions, Kosenkopf suggests that studying larger data sets with in-depth clinical information not limited to pancreatic cancer but also other malignancies can help establish the applicability of the gene. small 60Low signature in estimating cancer risk.

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