AUTHOR=Li Dingchang , Jiao Yanan , Gao Wenxing , Hu Shidong , Li Dingling , Zhao Wen , Chen Peng , Jin Lujia , Zhao Yingjie , Ma Zhaofu , Wu Xiansheng , Yan Yang , Sun Wen , Du Xiaohui , Dong Guanglong 

TITLE=Comprehensive analysis of the prognostic and immunotherapeutic implications of STAT family members in human colorectal cancer

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.951252

DOI=10.3389/fgene.2022.951252

ISSN=1664-8021

ABSTRACT=Background: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and the second leading cause of cancer mortality. Signal Transducer and Transcription Protein Enhancer (STAT) are a group of transcription factors reported to be implicated in cell signal transduction and gene transcription activation in several cancers. However, the level of expression, genetic alterations and biological function of different STATs, as well as their importance in prognosis, immune infiltration and immunotherapy for patients with CRC still remain unclear.
Methods: In our study, the mRNA and protein expression levels, genetic alterations, prognostic value, gene-gene interactions and protein-protein interactions network, and biological function of STATs in CRC were studied using the GEPIA, HPA, cBioPortal, PrognoScan, Kaplan Meier plotter, GeneMANIA, STRING and Metascape database. Meanwhile, we confirmed the expression of STATs in CRC by IHC. Finally, the relationship between STATs expression and immune infiltration as well as immunotherapy-associated indicators was also investigated. 
Results: The expression levels of STAT2/5A/5B are obviously down-regulated in CRC and the STAT1/3/4/5B expressions were significantly associated with the tumor stage of CRC patients. The abnormal expression of STAT2/4/5B in CRC patients is apparently related to the prognosis of CRC patients. The functions of STATs and its neighboring proteins are mainly related to lymphocyte activation, cytokine-mediated signaling pathway, positive regulation of immune response, regulation of cytokine production and growth hormone receptor signaling pathway in cancer. We also found that the expression of STATs was significantly associated with immune infiltration and immunotherapy response-associated indicators.
Conclusions: This study may help us further understand the molecular mechanism of CRC and provide new prognostic biomarkers and immunotherapy targets in CRC patients.