Dataset Information

The role of TGF-β pathway alterations in immune regulation as a potential pan-cancer biomarker in immunotherapy.

ABSTRACT:

Background

Depending 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.

Methods

In 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.

Results

The 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).

Conclusions

Collectively, our study suggested that mutations in TGF-β pathway may be associated with positive immune regulation and better efficacy of immunotherapy.

SUBMITTER: Liang Y

PROVIDER: S-EPMC8667138 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

The role of TGF-β pathway alterations in immune regulation as a potential pan-cancer biomarker in immunotherapy.

Liang Yan Y Li Wei W Qian Bing B Ming Jie J Zhao Zhengyi Z Yan Zhengqing Z Zhao Xiaochen X Chen Shiqing S Yin Yongmei Y

Annals of translational medicine 20211101 22

<h4>Background</h4>Depending 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.<h4>Methods</h4>In 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 ...[more]

PMID: 34988169

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Dataset Information

The role of TGF-β pathway alterations in immune regulation as a potential pan-cancer biomarker in immunotherapy.

Background

Methods

Results

Conclusions

Publications

The role of TGF-β pathway alterations in immune regulation as a potential pan-cancer biomarker in immunotherapy.

Similar Datasets

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