Elevated TNF-α level is correlated with NF-κB/p65 activation in patients with sporadic colorectal cancer.

Colorectal cancer (CRC) is a major global health issue, and inflammation plays a crucial role in its development. Nuclear factor-κB (NF-κB) activation, typically mediated by tumor necrosis factor-α (TNF-α), is involved in the inflammatory response leading to cancer. The present study aimed to investigate the TNF-α/NF-κB signaling in sporadic CRC. NF-κB activation was evaluated by measuring the phosphorylation of the p65 subunit at specific residues (pS536 and pS529) through phospho-flow cytometry. TNF-α protein levels were measured using flow cytometry/ELISA and TNF-α, NFKB1, and RELA gene expression was assessed using reverse transcription-quantitative PCR. The results were then correlated with the Tumor-Node-Metastasis (TNM) classification. The findings of the present study revealed that NF-κB activation was higher in tumoral tissue than in normal adjacent mucosa. TNF-α gene expression and protein levels were also elevated in patients with CRC, particularly in advanced stages. The present study demonstrated a positive correlation between TNF-α and NF-κB/p65. The analysis of TNM groups suggested that the correlation between TNF-α and p65 (pS536) plays an essential role in CRC tumorigenesis. By contrast, TNF-α and p65 (pS529) signaling was revealed to be relevant for CRC progression. Evaluating RELA and NFKB1 gene expression revealed molecular feedback during the inflammation response. The findings of the present study highlighted the TNF-α/NF-κB signaling pathway role in CRC development and may serve as a potential diagnostic and prognostic marker for the disease. Further research could provide valuable insights into the clinical implications of targeting this pathway in CRC diagnosis and treatment.