AGT serves as a potential biomarker and drives tumor progression in colorectal carcinoma

Int Immunopharmacol. 2021 Dec;101(Pt B):108225. doi: 10.1016/j.intimp.2021.108225. Epub 2021 Oct 13.

Abstract

Background: Colorectal carcinoma (CRC) is one of the most common aggressive tumors worldwide, and it is necessary to identify candidate biomarkers and therapeutic targets in CRC to improve patient outcomes.

Methods: The differentially expressed genes (DEGs) were obtained from CRC microarray. Functional enrichment was performed to explore the function of DEGs, and core genes were identified by Cytoscape. Then, the diagnosis and prognosis markers were identified by ROC curve and survival analyses. More importantly, a series of in vitro studies were conducted in CRC cells to explore the function of the selected biomarker. Further, the drug response was performed by Cancer Cell Line Encyclopedia (CCLE) and Cancer Therapy Response Portal (CTRP). In addition, the effect of drug on CRC cells was evaluated by functional experiments.

Results: The identified DEGs were mainly associated with the processes relating to tumorigenesis. 25 core genes were selected and angiotensinogen (AGT) was filtered out as a diagnosis and prognosis biomarker. Comprehensive in vitro experiments showed that AGT attributed to the proliferation, migration, and invasion of CRC cells, as well as angiogenesis of HUVECs induced by CRC conditional medium. Furthermore, drug response analysis implied that AGT expression was associated with isoliquiritigenins (ISL). Additionally, ISL could suppress the progression of CRC cells.

Conclusions: AGT is identified as diagnosis and prognosis prediction of CRC. Moreover, AGT attributes to the progression of CRC. Additionally, AGT exhibits fine drug response to ISL, and ISL is also evaluated as potential therapy drug in CRC.

Keywords: AGT; Bioinformatics; Biomarker; Colorectal cancer; Isoliquiritigenin.

MeSH terms

  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / metabolism*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • RNA Interference
  • Tissue Array Analysis

Substances

  • AGT protein, human
  • Biomarkers, Tumor
  • Angiotensinogen