# Glyphosate-Induced Metabolic and Immune Modulation in Hepatoma Cells: Identification of Key Genes as Diagnostic and Therapeutic Targets Using an In Silico Systems Biology Approach

## TL;DR

This study uses in silico methods to identify key genes affected by glyphosate in liver cancer cells, offering potential biomarkers for diagnosis and treatment.

## Contribution

The study identifies novel hub genes linked to glyphosate-induced metabolic and immune changes in hepatoma cells.

## Key findings

- Glyphosate exposure upregulates genes involved in glucose metabolism and stress responses.
- Downregulated genes are associated with lipid metabolism and immune regulation pathways.
- Hub genes show strong diagnostic potential for glyphosate exposure in liver cancer cells.

## Abstract

Glyphosate, one of the most widely used herbicides worldwide, has raised significant concerns regarding its potential involvement in hepatotoxicity and molecular changes associated with liver cancer biology. These concerns highlight the need to better understand its underlying molecular mechanisms in hepatoma cells. Emerging evidence suggests that glyphosate exposure may increase the risk of liver cancer and chronic liver disease. However, the precise molecular alterations and promising biomarkers associated with glyphosate-induced hepatic toxicity and disease remain largely unexplored. In this study, an RNA-Seq-based in silico systems biology approach was employed to elucidate glyphosate-induced differential transcriptional profiling in hepatoma cells. This analysis revealed significant transcriptional profiling characterized by the upregulated hub genes ATF3, JUNB, ALDOA, FOSB, PFKFB3, G6PD, ENO2, HK2, FOS and PGK1. These genes were primarily associated with glucose metabolism, TNF-α/NF-κB signaling, epithelial–mesenchymal transition (EMT) and cellular stress responses. Conversely, several key genes were significantly downregulated, including PIK3R1, FYN, CEBPA, MLXIPL, PPARA, CD36, PCK2, PNPLA3, NR1H4 and MGLL, which were involved in lipid metabolism, immune regulation and non-alcoholic fatty liver disease (NAFLD) pathways. Notably, all hub genes demonstrated strong diagnostic performance, highlighting their potential as sensitive biomarkers of glyphosate exposure. Collectively, this study provides comprehensive insights into gene expression changes associated with glyphosate exposure in hepatoma cells, linking them to hepatic metabolic dysregulation and immune modulation and suggesting a panel of hub genes with potential diagnostic and therapeutic significance.