Formin protein DIAPH1 positively regulates PD-L1 expression and predicts the therapeutic response to anti-PD-1/PD-L1 immunotherapy

Formin 蛋白 DIAPH1 正向调节 PD-L1 表达并预测对抗 PD-1/PD-L1 免疫疗法的治疗反应

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作者:Jie Mei, Yun Cai, Huiyu Wang, Rui Xu, Jiaofeng Zhou, Jiahui Lu, Xuejing Yang, Jiadong Pan, Chaoying Liu, Junying Xu, Yichao Zhu

Abstract

Formins are evolutionarily conserved genes and profoundly affect cancer progression. This study aims to explore the expressions, prognostic values, and immunological correlations of Formins in cancer. Specific Formins were dysregulated and immuno-biologically correlated in breast cancer (BRCA). Formins showed different expression patterns, namely some were enriched in immune cells while some were enriched in tumor cells. Among all Formins, DIAPH1 was enriched in tumor cells and associated with an inflamed tumor microenvironment (TME). DIAPH1 functioned as an oncogene in BRCA and mediated TGF-β1-induced epithelial-mesenchymal transformation (EMT) and PD-L1 expression. Moreover, DIAPH1 was overexpressed in most cancers and functioned as a novel pan-cancer immuno-marker, which could predict the response to anti-PD-1/PD-L1 immunotherapy. Overall, DIAPH1 functions as an oncogene and is immunologically correlated, which could be utilized as an alternative biomarker for predicting the immunotherapeutic response.

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