AUTHOR=Zhang Qixin , Qi Tiezheng , Long Yu , Li Xiaowen , Yao Yiyan , Wu Qi , Zou Anrong , Qthmane Belaydi , Liu Peihua 

TITLE=GATA3 Predicts the Tumor Microenvironment Phenotypes and Molecular Subtypes for Bladder Carcinoma

JOURNAL=Frontiers in Surgery

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/surgery/articles/10.3389/fsurg.2022.860663

DOI=10.3389/fsurg.2022.860663

ISSN=2296-875X

ABSTRACT=Background：GATA3 is a key player in antitumor immunology, and a rising number of studies show that it might be a key biomarker for bladder cancer. However, the immunological role of GATA3 in bladder cancer (BLCA) warrant further investigation.
Methods: We initially used pan-cancer analysis to analyze the expression pattern and immunological function of GATA3 based on mRNA sequencing data and clinical information gathered from the TCGA (The Cancer Genome Atlas). Then, in the BLCA tumor microenvironment (TME), we comprehensively associated GATA3 with immunomodulators, cancer immune cycles, tumor-infiltrating immune cells (TIICs), immune checkpoints, and T-cell inflamed scores. The role of GATA3 in predicting BLCA molecular subtypes and responsiveness to various treatment regimens was also investigated. We confirmed our findings in an external cohort and the Xiangya cohort to guarantee the correctness of our study.
Results: Based on a pan-cancer investigation, we discovered that GATA3 was preferentially expressed in the TME of numerous malignancies, including BLCA. High GATA3 expression was found to be adversely connected with immunological aspects such as immunomodulators, cancer immune cycles, TIICs, immune checkpoints, and T cell inflamed scores in the BLCA TME. This suggested that a high GATA3 level reflected a reduction in immunological infiltration. In addition, high GATA3 was more likely to be a luminal subtype, which meant it was less susceptible to cancer immunotherapy and neoadjuvant chemotherapy but more sensitive to targeted treatments, such as the blocking of the WNT-β-catenin, PPARG, and FGFR3 networks. All results summarized from the training cohort were successfully validated in external cohorts.
Conclusions: GATA3 may aid in the precision treatment for BLCA because it can accurately predict the clinical outcomes and the TME characteristics of BLCA.