AUTHOR=Zhu Jinfeng , Teng Hong , Zhu Xiaojian , Yuan Jingxuan , Zhang Qiong , Zou Yeqing 

TITLE=Pan-cancer analysis of Krüppel-like factor 3 and its carcinogenesis in pancreatic cancer

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1167018

DOI=10.3389/fimmu.2023.1167018

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Krüppel-like factor 3 (<italic>KLF3</italic>) is a key transcriptional repressor, which is involved in various biological functions such as lipogenesis, erythropoiesis, and B cell development, and has become one of the current research hotspots. However, the role of <italic>KLF3</italic> in the pan-cancer and tumor microenvironment remains unclear.</p></sec><sec><title>Methods</title><p>TCGA and GTEx databases were used to evaluate the expression difference of <italic>KLF3</italic> in pan-cancer and normal tissues. The cBioPortal database and the GSCALite platform analyzed the genetic variation and methylation modification of <italic>KLF3</italic>. The prognostic role of <italic>KLF3</italic> in pan-cancer was identified using Cox regression and Kaplan-Meier analysis. Correlation analysis was used to explore the relationship between <italic>KLF3</italic> expression and tumor mutation burden, microsatellite instability, and immune-related genes. The relationship between <italic>KLF3</italic> expression and tumor immune microenvironment was calculated by ESTIMATE, EPIC, and MCPCOUNTER algorithms. TISCH and CancerSEA databases analyzed the expression distribution and function of <italic>KLF3</italic> in the tumor microenvironment. TIDE, GDSC, and CTRP databases evaluated <italic>KLF3</italic>-predicted immunotherapy response and sensitivity to small molecule drugs. Finally, we analyzed the role of <italic>KLF3</italic> in pancreatic cancer by <italic>in vivo</italic> and <italic>in vitro</italic> experiments.</p></sec><sec><title>Results</title><p><italic>KLF3</italic> was abnormally expressed in a variety of tumors, which could effectively predict the prognosis of patients, and it was most obvious in pancreatic cancer. Further experiments verified that silencing <italic>KLF3</italic> expression inhibited pancreatic cancer progression. Functional analysis and gene set enrichment analysis found that <italic>KLF3</italic> was involved in various immune-related pathways and tumor progression-related pathways. In addition, based on single-cell sequencing analysis, it was found that <italic>KLF3</italic> was mainly expressed in CD4Tconv, CD8T, monocytes/macrophages, endothelial cells, and malignant cells in most of the tumor microenvironment. Finally, we assessed the value of <italic>KLF3</italic> in predicting response to immunotherapy and predicted a series of sensitive drugs targeting <italic>KLF3</italic>.</p></sec><sec><title>Conclusion</title><p>The role of <italic>KLF3</italic> in the tumor microenvironment of various types of tumors cannot be underestimated, and it has significant potential as a biomarker for predicting the response to immunotherapy. In particular, it plays an important role in the progression of pancreatic cancer.</p></sec>