New evidence points to a link between mitochondria and cancer

It is estimated that more than 600,000 people die from cancer
each year in the United States as of 2022.
        

Polygenic expression signatures in tumors are associated with aggressive disease and poor patient outcomes, and it has the potential to become a biomarker for hereditary
cancers.

Mitochondria are the main source of energy for human cells and play an important role
in the metabolism of cancer cells.
In a recent study published in PLOS ONE, researchers from around the world, including Dario C.
Altieri, M.
D.
, president and CEO of the Ellen and Ronald Caplan Cancer Center, and Robert and Penny Fox, special professors at the Wistar Institute, have identified a specific genetic signature indicating that mitochondrial weight programming in tumors is associated with poor patient outcomes
。

"To our knowledge, this is the first time that genetic signatures of mitochondrial dysfunction have been found to be associated
with aggressive cancer subtypes, treatment resistance, and, unfortunately, low patient survival.
Although our work has focused on the mitochondrial protein Mic60 in this reaction, we know that dysfunctional mitochondria are typically produced during tumor growth, suggesting that this is a common feature of cancer," Altieri said
.

The study was inspired by earlier studies into the role
of the Mic60 protein in tumor cell proliferation, motility, and metastasis.
MIC60, also known as mitofilin or inner membrane mitochondrial protein (IMMT), is a key protein necessary for mitochondrial structure and therefore affects mitochondrial function and tumor metabolism
.

Dr Andrew Kossenkov, first author of the paper, assistant professor in the Wistar Gene Expression and Regulation Project and scientific director of the Institute's Bioinformatics Facility, said: "After the original discovery of a strong correlation between low levels of Mic60 in cancer tissue, we were curious whether we could identify a specific set of functions of genes downstream of Mic60 and whether the low genomic features of Mic60 are clinically relevant – i.
e.
, whether it is associated with survival, Clinical data related to cancer subtypes, treatment response, etc.
– we did
it.
”

Armed with this knowledge, the team—along with collaborators from across Canada, Italy, and the United States—analyzed tumor cells
from three separate cohorts of pancreatic ductal adenocarcinoma (PDAC) patients.
They showed that a low MIC60 signal in one 11 genes was associated with aggressive disease, local inflammation, treatment failure, and shortened survival — ultimately demonstrating the clinical relevance
of the protein.
Therefore, the Mic60-low gene marker can be used as a simple tool or biomarker to estimate cancer risk in PDAC and potentially other types of cancer, including glioblastoma
.

Kossenkov explains: "Genetic signatures can be used to gain insight into specific tumor qualities
.
If widely developed, tested, and validated, this (Mic60-low gene signature) could become a potentially simple point-of-service molecular tool
for pancreatic cancer prognosis or patient risk stratification and treatment response prediction.
”

"While the widespread use of this new Mic60-low gene signature certainly requires further confirmation in a larger patient population, we hope that this simple, easily implementable molecular tool will help in clinical stratification
of patients at higher risk of severe and progressive disease," Altieri elaborated.

Regarding the way forward, Kossenkov suggests studying a broader dataset containing a wide range of clinical information, not limited to pancreatic cancer, but also other malignancies, which could help demonstrate the applicability of the 11-gene Mic60-low feature in estimating cancer risk
.

Reference: Mitochondrial fitness and cancer risk