Multi-omics integration analysis robustly predicts high-grade patient survival and identifies CPT1B effect on fatty acid metabolism in bladder cancer
Patients with high-grade bladder cancer (BLCA) have a relatively low life expectancy despite available treatments, which means better prognostic markers and therapeutic targets are needed. However, knowledge of the molecular processes of tumor progression in BCLA is limited. One hallmark of tumor development is the reprogramming of the metabolism to cover the altered energy demand of cancer cells. But little is known about metabolic perturbations leading to bladder cancer (BLCA) progression. Identifying grade-specific metabolic patterns might help explain pathophysiological processes and facilitate the development of more effective therapies. Because integrated multi-OMICS data provide a system level perspective, Vantaku et al. used this method to predict BCLA survival based on metabolic and genetic signatures.
Comparing low- and high-grade BLCA revealed clear differences in metabolic, lipidomic and transcriptomic gene signatures. Changes in the levels of 519 metabolites and 19 lipids suggested many pathways involved. Unique deregulation of a subset reflected tumor progression in high-grade BLCA. A gene signature of 11 upregulated genes and 16 downregulated genes were found to be associated with poor survival in BLCA cohorts. Interestingly, carnitine palmitoyl transferase 1B (CPT1B) expression was significantly lower in high-grade BLCA and correlated with lower life expectancy. In consistency, lower levels of palmitoyl and octanoyl carnitines indicated reduced fatty acid ß-oxidation (FAO), which is limited by CPT1B. Known cancer characteristics like excessive cell proliferation and formation of metastasis were inhibited by CPT1B overexpression in high-grade BLCA.
The multi-OMICS approach of this study identified metabolic and genetic signatures of high-grade BLCA, which could improve survival prognosis. Considering that tumor progression involves impaired FAO, increasing the CPT1B levels in high-grade BLCA might be a potential therapeutic intervention.
Metabolomics is a great tool to predict tumor progression, therefore you should also read Prediction of cancer survival rate with metabolomics at our literature page.
Vantaku V. et al.: Multi-omics integration analysis robustly predicts high-grade patient survival and identifies CPT1B effect on fatty acid metabolism in Bladder Cancer. (2019) Clinical Cancer Research | https://doi.org/10.1158/1078-0432.CCR-18-1515