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Image: Dr.
Dario Altieri, President and CEO of the Wistar Institute
Mitochondria are key components in the production of energy in human cells and play an important role
in cancer cell metabolism.
In a research paper published in PLOS ONE, Dario C.
Altieri, M.
D.
, along with national and international collaborators, distinguished a specific genetic signature that indicates the programming
of mitochondrial body weight in tumors 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 primarily on mitochondrial proteins on Mic60 in this response, we know that dysfunctional mitochondria are often produced during tumor growth, suggesting that this is a common feature of
cancer.
”
This paper stems from past studies of the role of the protein Mic60 in tumor cell proliferation, motility and metastasis
.
MIC60, also known as mitofilin or inner membrane mitochondrial protein (IMT), is a key protein that is critical for mitochondrial structure and therefore has downstream effects
on mitochondrial function and tumor metabolism.
"After the initial discovery, in the low levels of strongly associated Mic60 in cancer tissue, we were curious if we could identify a small subset of Mic60 downstream genes and if the Mic60-low gene panel feature was clinically relevant — i.
e.
, if it correlated with clinical data such as survival, cancer subtype, response to treatment, etc
.
— and we did.
"
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 found that an 11-gene Mic60-low signal was associated with aggressive disease, local inflammation, treatment failure, and shortened survival—conclusively demonstrating the protein's clinical relevance
.
Thus, the Mic60-low gene marker can be used as a simple tool or biomarker to estimate cancer risk for PDAC and potentially other types of cancer, including glioblastoma
.
"Genetic signatures can be used to gain insight into specific tumor quality," Kossenkov explains
.
"If widely developed, tested, and validated, this [Mic60-low gene signature] could be a potentially simple point-of-service molecular tool for pancreatic cancer prognosis or patient risk stratification and treatment response prediction
.
"
While the broad applicability of this new MIC 60-low gene marker certainly needs to be further confirmed in a larger patient population, we hope that this simple, easy-to-implement molecular tool will help clinically stratify
patients at higher risk of severe and progressive disease.
" ”
Regarding future research directions, Kossenkov suggested that the study contains a broader dataset of extensive clinical information, not limited to pancreatic cancer, but also other malignancies, to help demonstrate the applicability of the 11 gene MIC60-low signature in estimating cancer risk
.