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

  • Authors:
    • Uriel Francisco Santana‑Bejarano
    • David Fernandez‑Sanchez
    • Lucina Bobadilla‑Morales
    • Alejandro Brukman‑Jimenez
    • Jesús Alonso Valenzuela‑Pérez
    • Jorge Román Corona‑Rivera
    • Alfredo Corona‑Rivera
  • View Affiliations / Copyright

    Affiliations: Cytogenetics Unit, Civil Hospital of Guadalajara ‘Dr. Juan I. Menchaca’, Guadalajara, Jalisco 44340, Mexico, Cytogenetics and Genomics Laboratory, Department of Molecular Biology and Genomics, Human Genetics Institute ‘Dr. Enrique Corona‑Rivera’, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco 44340, Mexico, Pathological Anatomy, Colon and Rectum Service, Civil Hospital of Guadalajara ‘Dr. Juan I. Menchaca’, Guadalajara, Jalisco 44340, Mexico
    Copyright: © Santana‑Bejarano et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 30
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    Published online on: March 9, 2026
       https://doi.org/10.3892/mco.2026.2939
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Abstract

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.
View Figures

Figure 1

NF-κB/p65 activation in sporadic
colorectal cancer. (A) NF-κB/p65 (pS536) and (pS529) activation
evaluated by TNM classification. (B) Phospho-flow cytometric
histograms of the mean NF-κB/p65 (pS536) activation reported no
significant differences in early vs. advanced stages using
Mann-Whitney U test (P>0.05). (C) Phospho-flow cytometric
histograms of the mean NF-κB/p65 (pS529) activation reported
significant differences in early vs. advanced stages using
Mann-Whitney U test (P<0.05). NF-κB, nuclear factor-κB;
pS536/529, phosphorylated serine 536/529; TNM,
tumor-node-metastasis.

Figure 2

TNF-α cell surface levels in sporadic
colorectal cancer. TNF-α cell surface activity in CRC group vs.
normal adjacent mucosa as a calibrator was evaluated using Wilcoxon
matched-pairs test (P<0.05). (A) TNF-α cell surface mean
activity (%) comparative graph evaluating TNM groups and (B) Flow
cytometric histograms of the mean TNF-α cell surface protein
reported significant differences in early compared to advanced
stages using unpaired Student' t-test (P<0.05). TNF-α, tumor
necrosis factor α; TNM, tumor-node-metastasis.

Figure 3

TNF-α serum levels in sporadic
colorectal cancer. The advanced stages group level is statistically
higher compared with that in the early stages group and the control
group. The early stages group differed significantly from that in
the control group. Statistically significant differences among
groups were indicated based on Tukey's test.

Figure 4

Relative gene expression levels in
sporadic colorectal cancer. The Livak method was used to calculate
the relative gene expression of TNFA, RELA and NFKB1
in the CRC group compared with normal adjacent mucosa as a
calibrator. TNFA and RELA exhibited significantly
upregulated expression in advanced CRC stages compared with early
stages using unpaired Student's t-test (P<0.05). No significant
differences were observed in NFKB1 between groups using
unpaired Student's t-test (P>0.05). TNFA, tumor necrosis
factor-α; RELA, RELA p65 proto-oncogene; NFKB1,
nuclear factor-κB subunit 1.

Figure 5

Molecular model of NF-κB activation
in sporadic CRC.TNF-α/NF-κB signaling is regulated by IKK and CK2
activity, which in turn phosphorylates NF-κB/p65 (S536) and (S529)
residues, respectively. The model indicates the feedback between
NF-κB/p65 activation and TNF-α upregulation. CRC, colorectal
cancer; TNFA/TNF-α, tumor necrosis factor-α; NF-κB, nuclear
factor-κB; pS536/529, phosphorylated serine 536/529; RELA,
RELA p65 proto-oncogene; NFKB1, nuclear factor-κB subunit
1.
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Spandidos Publications style
Santana‑Bejarano UF, Fernandez‑Sanchez D, Bobadilla‑Morales L, Brukman‑Jimenez A, Valenzuela‑Pérez JA, Corona‑Rivera JR and Corona‑Rivera A: Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer. Mol Clin Oncol 24: 30, 2026.
APA
Santana‑Bejarano, U.F., Fernandez‑Sanchez, D., Bobadilla‑Morales, L., Brukman‑Jimenez, A., Valenzuela‑Pérez, J.A., Corona‑Rivera, J.R., & Corona‑Rivera, A. (2026). Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer. Molecular and Clinical Oncology, 24, 30. https://doi.org/10.3892/mco.2026.2939
MLA
Santana‑Bejarano, U. F., Fernandez‑Sanchez, D., Bobadilla‑Morales, L., Brukman‑Jimenez, A., Valenzuela‑Pérez, J. A., Corona‑Rivera, J. R., Corona‑Rivera, A."Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer". Molecular and Clinical Oncology 24.5 (2026): 30.
Chicago
Santana‑Bejarano, U. F., Fernandez‑Sanchez, D., Bobadilla‑Morales, L., Brukman‑Jimenez, A., Valenzuela‑Pérez, J. A., Corona‑Rivera, J. R., Corona‑Rivera, A."Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer". Molecular and Clinical Oncology 24, no. 5 (2026): 30. https://doi.org/10.3892/mco.2026.2939
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Spandidos Publications style
Santana‑Bejarano UF, Fernandez‑Sanchez D, Bobadilla‑Morales L, Brukman‑Jimenez A, Valenzuela‑Pérez JA, Corona‑Rivera JR and Corona‑Rivera A: Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer. Mol Clin Oncol 24: 30, 2026.
APA
Santana‑Bejarano, U.F., Fernandez‑Sanchez, D., Bobadilla‑Morales, L., Brukman‑Jimenez, A., Valenzuela‑Pérez, J.A., Corona‑Rivera, J.R., & Corona‑Rivera, A. (2026). Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer. Molecular and Clinical Oncology, 24, 30. https://doi.org/10.3892/mco.2026.2939
MLA
Santana‑Bejarano, U. F., Fernandez‑Sanchez, D., Bobadilla‑Morales, L., Brukman‑Jimenez, A., Valenzuela‑Pérez, J. A., Corona‑Rivera, J. R., Corona‑Rivera, A."Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer". Molecular and Clinical Oncology 24.5 (2026): 30.
Chicago
Santana‑Bejarano, U. F., Fernandez‑Sanchez, D., Bobadilla‑Morales, L., Brukman‑Jimenez, A., Valenzuela‑Pérez, J. A., Corona‑Rivera, J. R., Corona‑Rivera, A."Elevated TNF‑&alpha; level is correlated with NF‑&kappa;B/p65 activation in patients with sporadic colorectal cancer". Molecular and Clinical Oncology 24, no. 5 (2026): 30. https://doi.org/10.3892/mco.2026.2939
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