Pan-cancer multi-omics analyses reveal crosstalk between the Hippo and immune signaling pathways in the tumor microenvironment

Chengyu Wang; Tong Zhu; Zhangxiang Zhao; Bo Chen; Tingting Chen; Qi Dong; Mingyue Liu; Shuping Zhuang; Fan Yang; Yaoyao Liu; Min Yang; Yunyan Gu; Haihai Liang

doi:10.1002/1873-3468.14249

Pan-cancer multi-omics analyses reveal crosstalk between the Hippo and immune signaling pathways in the tumor microenvironment

FEBS Lett. 2022 Feb;596(4):449-464. doi: 10.1002/1873-3468.14249. Epub 2021 Dec 27.

Authors

Chengyu Wang^{1

2}, Tong Zhu³, Zhangxiang Zhao⁴, Bo Chen¹, Tingting Chen¹, Qi Dong¹, Mingyue Liu¹, Shuping Zhuang¹, Fan Yang¹, Yaoyao Liu¹, Min Yang⁵, Yunyan Gu¹, Haihai Liang⁴

Affiliations

¹ Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, China.
² Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, China.
³ Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, China.
⁴ The Sino-Russian Medical Research Center of Jinan University, The Institute of Chronic Disease of Jinan University, The First Affiliated Hospital of Jinan University, Guangzhou, China.
⁵ Guangdong Cardiovascular Institute, Guangdong Province People's Hospital, Guangzhou, China.

PMID: 34855209
DOI: 10.1002/1873-3468.14249

Abstract

The Hippo signaling pathway is critical for carcinogenesis. However, the roles of the Hippo signaling pathway in the tumor immune microenvironment have been rarely investigated. This study systematically analyzed the relationship between the Hippo signaling pathway and immune cell infiltration across 32 cancer types. Both bioinformatics analyses and biological experiments revealed that the downstream effector of Hippo signaling YAP1 might inhibit CD8+ T cell infiltration by upregulating the expression of the transcription factor CREB1 in uterine corpus endometrial carcinoma. In addition, esophageal carcinoma (ESCA) patients were classified into three subtypes based on the Hippo-immune gene panel. The subtypes of ESCA had distinct characteristics in immune cell infiltration, immune pathways, and prognosis. Thus, this study also reveals a new classification of the immune subtypes with prognostic characteristics in ESCA.

Keywords: Hippo signaling pathway; cancer; immune; multi-omics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / pathology
Carcinogenesis / genetics
Carcinogenesis / immunology
Carcinogenesis / pathology
Cell Movement
Cyclic AMP Response Element-Binding Protein / genetics
Cyclic AMP Response Element-Binding Protein / immunology
Endometrial Neoplasms / genetics*
Endometrial Neoplasms / immunology
Endometrial Neoplasms / pathology
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / immunology
Esophageal Neoplasms / pathology
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Hippo Signaling Pathway / genetics*
Humans
Neoplasm Invasiveness
Neoplasms / classification
Neoplasms / genetics*
Neoplasms / immunology
Neoplasms / pathology
Prognosis
Proteomics / methods
Receptors, Antigen, B-Cell / classification
Receptors, Antigen, B-Cell / genetics
Receptors, Antigen, B-Cell / immunology
Receptors, Antigen, T-Cell / classification
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / immunology
Survival Analysis
Terminology as Topic
Tumor Microenvironment / genetics*
YAP-Signaling Proteins / genetics*
YAP-Signaling Proteins / immunology

Substances

CREB1 protein, human
Cyclic AMP Response Element-Binding Protein
Receptors, Antigen, B-Cell
Receptors, Antigen, T-Cell
YAP-Signaling Proteins
YAP1 protein, human