American Association for Cancer Research
Browse
10780432ccr191543-sup-222119_2_supp_5712048_pw8sdj.pdf (139.23 kB)

Figure S5 from Altered Gene Expression along the Glycolysis–Cholesterol Synthesis Axis Is Associated with Outcome in Pancreatic Cancer

Download (139.23 kB)
journal contribution
posted on 2023-03-31, 21:30 authored by Joanna M. Karasinska, James T. Topham, Steve E. Kalloger, Gun Ho Jang, Robert E. Denroche, Luka Culibrk, Laura M. Williamson, Hui-Li Wong, Michael K.C. Lee, Grainne M. O'Kane, Richard A. Moore, Andrew J. Mungall, Malcolm J. Moore, Cassia Warren, Andrew Metcalfe, Faiyaz Notta, Jennifer J. Knox, Steven Gallinger, Janessa Laskin, Marco A. Marra, Steven J.M. Jones, Daniel J. Renouf, David F. Schaeffer

Kaplan-Meier curve demonstrating the differences in the time to relapse in resectable PDAC. Data for ICGC PACA-CA cohort with available relapse data are shown (N=118).

History

ARTICLE ABSTRACT

Identification of clinically actionable molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcome. Intertumoral metabolic heterogeneity contributes to cancer survival and the balance between distinct metabolic pathways may influence PDAC outcome. We hypothesized that PDAC can be stratified into prognostic metabolic subgroups based on alterations in the expression of genes involved in glycolysis and cholesterol synthesis. We performed bioinformatics analysis of genomic, transcriptomic, and clinical data in an integrated cohort of 325 resectable and nonresectable PDAC. The resectable datasets included retrospective The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) cohorts. The nonresectable PDAC cohort studies included prospective COMPASS, PanGen, and BC Cancer Personalized OncoGenomics program (POG). On the basis of the median normalized expression of glycolytic and cholesterogenic genes, four subgroups were identified: quiescent, glycolytic, cholesterogenic, and mixed. Glycolytic tumors were associated with the shortest median survival in resectable (log-rank test P = 0.018) and metastatic settings (log-rank test P = 0.027). Patients with cholesterogenic tumors had the longest median survival. KRAS and MYC-amplified tumors had higher expression of glycolytic genes than tumors with normal or lost copies of the oncogenes (Wilcoxon rank sum test P = 0.015). Glycolytic tumors had the lowest expression of mitochondrial pyruvate carriers MPC1 and MPC2. Glycolytic and cholesterogenic gene expression correlated with the expression of prognostic PDAC subtype classifier genes. Metabolic classification specific to glycolytic and cholesterogenic pathways provides novel biological insight into previously established PDAC subtypes and may help develop personalized therapies targeting unique tumor metabolic profiles.See related commentary by Mehla and Singh, p. 6

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC