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

BACKGROUND

Krüppel-like factor 3 () 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 in the pan-cancer and tumor microenvironment remains unclear.

METHODS

TCGA and GTEx databases were used to evaluate the expression difference of in pan-cancer and normal tissues. The cBioPortal database and the GSCALite platform analyzed the genetic variation and methylation modification of . The prognostic role of in pan-cancer was identified using Cox regression and Kaplan-Meier analysis. Correlation analysis was used to explore the relationship between expression and tumor mutation burden, microsatellite instability, and immune-related genes. The relationship between expression and tumor immune microenvironment was calculated by ESTIMATE, EPIC, and MCPCOUNTER algorithms. TISCH and CancerSEA databases analyzed the expression distribution and function of in the tumor microenvironment. TIDE, GDSC, and CTRP databases evaluated -predicted immunotherapy response and sensitivity to small molecule drugs. Finally, we analyzed the role of in pancreatic cancer by and experiments.

RESULTS

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 expression inhibited pancreatic cancer progression. Functional analysis and gene set enrichment analysis found that was involved in various immune-related pathways and tumor progression-related pathways. In addition, based on single-cell sequencing analysis, it was found that 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 in predicting response to immunotherapy and predicted a series of sensitive drugs targeting .

CONCLUSION

The role of 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.