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| Status |
Public on Feb 03, 2023 |
| Title |
Mitochondrial fitness and risk of pancreatic ductal adenocarcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Changes in metabolism are a hallmark of cancer, but molecular signatures of altered bioenergetics to aid in clinical decision-making do not currently exist. We recently identified a group of human tumors with constitutively reduced expression of the mitochondrial structural protein, Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT). These Mic60-low tumors exhibit severe loss of mitochondrial fitness, paradoxically accompanied by increased metastatic propensity and upregulation of a unique transcriptome of Interferon (IFN) signaling and Senescence-Associated Secretory Phenotype (SASP). Here, we show that an optimized, 11-gene signature of Mic60-low tumors is differentially expressed in multiple malignancies, compared to normal tissues, and correlates with poor outcome. When analyzed in three independent patient cohorts of pancreatic ductal adenocarcinoma (PDAC), the Mic60-low gene signature was associated with aggressive molecular variants of PDAC, local inflammation, FOLFIRINOX failure and shortened survival, independently of age, gender, or stage. Therefore, the 11-gene Mic60-low signature may provide an easily accessible molecular tool to stratify patient risk in PDAC and potentially other malignancies.
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| Overall design |
RNA-seq of Mic60 WT and KO cells.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/36223343/
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| Contributor(s) |
Altieri D, Kossenkov A |
| Citation(s) |
36223343 |
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| Submission date |
Feb 25, 2022 |
| Last update date |
May 05, 2023 |
| Contact name |
Priyankara J Wickramasinghe |
| E-mail(s) |
priyaw@wistar.org
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| Phone |
2154956837
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| Organization name |
The Wistar Institute
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| Department |
Bioinformatics
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| Lab |
Genomics
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| Street address |
3601 Spruce Street
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA810442 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE197465_Mic60_RNAseq.txt.gz |
356.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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