Multiomics subtyping for clinically prognostic cancer subtypes and personalized therapy: A systematic review and meta-analysis.

PURPOSE: Multiomics cancer subtyping is becoming increasingly popular for directing state-of-the-art therapeutics. However, these methods have never been systematically assessed for their ability to capture cancer prognosis for identified subtypes, which is essential to effectively treat patients. METHODS: We systematically searched PubMed, The Cancer Genome Atlas, and Pan-Cancer Atlas for multiomics cancer subtyping studies from 2010 through 2019. Studies comprising at least 50 patients and examining survival were included. Pooled Cox and logistic mixed-effects models were used to compare the ability of multiomics subtyping methods to identify clinically prognostic subtypes, and a structural equation model was used to examine causal paths underlying subtyping method and mortality. RESULTS: A total of 31 studies comprising 10,848 unique patients across 32 cancers were analyzed. Latent-variable subtyping was significantly associated with overall survival (adjusted hazard ratio, 2.81; 95% CI, 1.16-6.83; P = .023) and vital status (1 year adjusted odds ratio, 4.71; 95% CI, 1.34-16.49; P = .015; 5 year adjusted odds ratio, 7.69; 95% CI, 1.83-32.29; P = .005); latent-variable-identified subtypes had greater associations with mortality across models (adjusted hazard ratio, 1.19; 95% CI, 1.01-1.42; P = .050). Our structural equation model confirmed the path from subtyping method through multiomics subtype (߈ = 0.66; P = .048) on survival (߈ = 0.37; P = .008). CONCLUSION: Multiomics methods have different abilities to define clinically prognostic cancer subtypes, which should be considered before administration of personalized therapy; preliminary evidence suggests that latent-variable methods better identify clinically prognostic biomarkers and subtypes.