ArticleAnnals of translational medicine2021
The role of TGF-β pathway alterations in immune regulation as a potential pan-cancer biomarker in immunotherapy.
Article in Annals of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors at 4 institutions in 1 country.
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Abstract
backgroundDepending on the context, the transforming growth factor beta (TGF-β) signaling pathway is involved in opposing cell processes of tumor suppression and tumor promotion. However, the effects of TGF-β pathway on immunotherapy efficacy have not yet been systematically investigated.
methodsIn this study, we have extracted the available data of whole-exome sequencing, messenger RNA (mRNA) expression, baseline characterization, and prognosis information of 10,912 pan-cancer patients from The Cancer Genome Atlas to explore the role of TGF-β pathway in immune regulation. Formalin-fixed, paraffin-embedded tissue samples from 6,717 Chinese cancer patients assayed by next-generation sequencing (NGS) were used as a validation cohort (3DMed cohort). Data sets from the public MSK (Memorial Sloan Kettering Cancer Center) cohort (N=1,610) were used to explore the association of TGF-β pathway with immunotherapy effects.
resultsThe results showed that TGF-β pathway alteration was significantly correlated with high microsatellite instability (MSI), high tumor mutational burden, and high neoantigen burden (TNB) (P<0.001 for each). Consistently, the pathway mutations were associated with distinct patterns of immune-related gene expression and tumor-infiltrating immune cells. Patients with TGF-β pathway mutations exhibited significantly worse prognosis than did the wild-type patients regardless of the interventions [overall survival (OS): hazard ratio (HR) 1.20; 95% confidence interval (CI): 1.08-1.33; P=0.001]. However, when treated with immune checkpoint inhibitors (ICIs), superior survival benefit was observed in patients from the mutation group versus the wild-type group (OS: HR 0.73; 95% CI: 0.61-0.88; P=0.001).
conclusionsCollectively, our study suggested that mutations in TGF-β pathway may be associated with positive immune regulation and better efficacy of immunotherapy.
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