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Research Article


Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study

Akeem Moradehun Bamiro, Zul Izhar Mohd Ismail, Sharifah Emilia Tuan Sharif, Tengku Ahmad Damitri Al-astani Tengku Din, Nasibah Mohamad, Luqman Afiq Mohamad Ishak, Samir Acherar, Philippe Arnoux, Céline Frochot, Norhafiza Mat Lazim.


Abstract
Background:
Oral squamous cell carcinoma of the tongue is the most common type of head and neck malignancy and is associated with poor survival. Although inflammatory blood indices, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have prognostic value in human cancers, their role in preclinical oral cancer models is poorly defined.

Aim:
To evaluate the prognostic performance of post-induction NLR, PLR, and LMR for short-term survival in rats with 4-nitroquinoline-1-oxide (4NQO)-induced tongue squamous cell carcinoma induced by 4-nitroquinoline-1-oxide (4NQO).

Method:
Female Sprague Dawley rats were exposed to 50 ppm 4NQO in drinking water for 20 weeks. Complete blood counts were obtained at baseline and after tumor induction to compute systemic inflammatory indices. 18 rats were included in the survival study, and the overall survival was defined as the time from the post-induction blood assessment (start of the 42-day observation period) to death/euthanasia, with animals alive at day 42 right-censored. Receiver operating characteristic (ROC) analysis with Youden’s index was used to select the most sensitive model and derive an optimal cutoff for 42-day mortality. Kaplan–Meier curves with log-rank testing were used to compare survival between the biomarker strata.

Results:
The receiver operating characteristic (ROC) analysis demonstrated good discrimination for NLR (area under the curve [AUC] 0.901), while PLR (AUC 0.358) and LMR (AUC 0.265) showed poor discrimination. The optimal NLR cutoff was 0.5463 (sensitivity, 0.889; 1-specificity, 0.111; Youden’s index, 0.778). Kaplan–Meier analysis showed markedly poorer survival in rats with NLR > 0.55, with 8/9 deaths versus 1/9 deaths in the ≤ 0.55 group (log-rank P < 0.001).

Conclusion:
Post-induction NLR derived from routine complete blood counts modestly discriminated 42-day survival in a 4NQO-induced rat model of tongue squamous cell carcinoma, supporting its use as a potential prognostic biomarker in resource-limited preclinical settings and as a basis for larger, controlled studies.

Key words: 4-Nitroquinoline-1-oxide; Blood cell count; Clinical decision rule; Mouth neoplasm; Squamous cell carcinoma.


 
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How to Cite this Article
Pubmed Style

Bamiro AM, Ismail ZIM, Sharif SET, , Mohamad N, Ishak LAM, Acherar S, Arnoux P, Frochot C, Lazim NM. Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study. Open Vet. J.. 2026; 16(5): 3155-3165. doi:10.5455/OVJ.2026.v16.i5.56

Web Style

Bamiro AM, Ismail ZIM, Sharif SET, , Mohamad N, Ishak LAM, Acherar S, Arnoux P, Frochot C, Lazim NM. Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study. https://www.openveterinaryjournal.com/?mno=286546 [Access: June 01, 2026]. doi:10.5455/OVJ.2026.v16.i5.56

AMA (American Medical Association) Style

Bamiro AM, Ismail ZIM, Sharif SET, , Mohamad N, Ishak LAM, Acherar S, Arnoux P, Frochot C, Lazim NM. Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study. Open Vet. J.. 2026; 16(5): 3155-3165. doi:10.5455/OVJ.2026.v16.i5.56


Vancouver/ICMJE Style

Bamiro AM, Ismail ZIM, Sharif SET, , Mohamad N, Ishak LAM, Acherar S, Arnoux P, Frochot C, Lazim NM. Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study. Open Vet. J.. (2026), [cited June 01, 2026]; 16(5): 3155-3165. doi:10.5455/OVJ.2026.v16.i5.56


Harvard Style

Bamiro, A. M., Ismail, . Z. I. M., Sharif, . S. E. T., , Mohamad, . N., Ishak, . L. A. M., Acherar, . S., Arnoux, . P., Frochot, . C. & Lazim, . N. M. (2026) Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study. Open Vet. J., 16 (5), 3155-3165. doi:10.5455/OVJ.2026.v16.i5.56


Turabian Style

Bamiro, Akeem Moradehun, Zul Izhar Mohd Ismail, Sharifah Emilia Tuan Sharif, Tengku Ahmad Damitri Al-astani Tengku Din, Nasibah Mohamad, Luqman Afiq Mohamad Ishak, Samir Acherar, Philippe Arnoux, Céline Frochot, and Norhafiza Mat Lazim. 2026. Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study. Open Veterinary Journal, 16 (5), 3155-3165. doi:10.5455/OVJ.2026.v16.i5.56


Chicago Style

Bamiro, Akeem Moradehun, Zul Izhar Mohd Ismail, Sharifah Emilia Tuan Sharif, Tengku Ahmad Damitri Al-astani Tengku Din, Nasibah Mohamad, Luqman Afiq Mohamad Ishak, Samir Acherar, Philippe Arnoux, Céline Frochot, and Norhafiza Mat Lazim. "Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study." Open Veterinary Journal 16 (2026), 3155-3165. doi:10.5455/OVJ.2026.v16.i5.56


MLA (The Modern Language Association) Style

Bamiro, Akeem Moradehun, Zul Izhar Mohd Ismail, Sharifah Emilia Tuan Sharif, Tengku Ahmad Damitri Al-astani Tengku Din, Nasibah Mohamad, Luqman Afiq Mohamad Ishak, Samir Acherar, Philippe Arnoux, Céline Frochot, and Norhafiza Mat Lazim. "Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study." Open Veterinary Journal 16.5 (2026), 3155-3165. Print. doi:10.5455/OVJ.2026.v16.i5.56


APA (American Psychological Association) Style

Bamiro, A. M., Ismail, . Z. I. M., Sharif, . S. E. T., , Mohamad, . N., Ishak, . L. A. M., Acherar, . S., Arnoux, . P., Frochot, . C. & Lazim, . N. M. (2026) Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Experimental Tongue Squamous Cell Carcinoma Induced by 4-Nitroquinoline-1-Oxide—A Pilot Study. Open Veterinary Journal, 16 (5), 3155-3165. doi:10.5455/OVJ.2026.v16.i5.56


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