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. 2025 Jun 16;17(6):e86149.
doi: 10.7759/cureus.86149. eCollection 2025 Jun.

Evaluating the Role of Neurogenic Locus Notch Homolog Protein 1 in Oral Cancer Progression and Therapeutic Opportunities

Mostafa Ahmed Abdellah Ahmed  1 , Tayyaba Rafiq  2 , Noor Ul Ain Rashid  3 , Madeeha Minhas  4   5   6 , Seemi Tanvir  7 , Sajid Ali Majeedano  8 , Asma Ali  9 , Muhmmad Hussain Shah  10
Affiliations

Evaluating the Role of Neurogenic Locus Notch Homolog Protein 1 in Oral Cancer Progression and Therapeutic Opportunities

Mostafa Ahmed Abdellah Ahmed et al. Cureus. .

Abstract

Background and aim: The most common type of malignancy on a global scale is oral cancer, as its incidence level is high worldwide. The neurogenic locus notch homolog protein 1 (NOTCH1) plays a key role in cell maturation and the regulation of the immune system; however, its functions are still not fully understood. This research evaluated the expression of NOTCH1 across two types of oral cancer (oral squamous cell carcinoma {OSCC} versus mucoepidermoid carcinoma {MEC}) and healthy controls to observe its correlation with immune suppression and patterns of disease progression.

Methods: This case-control study was conducted over a seven-month period from March 2023 to September 2023. A total of 120 participants were enrolled and divided into three equal groups, i.e., 40/120 (33.34%) OSCC cases, 40/120 (33.33%) MEC cases, and 40/120 (33.33%) healthy controls. The RNA extraction was done using a protocol, and blood and tumor tissues were taken for the purpose, after which cDNA was produced. The analysis was performed using NOTCH1-specific primers by quantitative real-time PCR (RT-qPCR). SPSS version 20 (Armonk, NY: IBM Corp.) was used for the calculation of expression quantities by employing the 2-ΔΔCt method. To analyze the data, the ANOVA method was used. A p-value of <0.05 was considered significant.

Results: The expression levels of NOTCH1 mRNA were seen to be substantially different across groups, with a mean of 3.67±0.59, while MEC patients displayed lower overexpression at 2.48±0.53, and controls maintained baseline expression at 1.00±0.42. NOTCH1 in stage IV cancers was more upregulated (4.03±0.48) than in stage III (3.26±0.56; p<0.001).

Conclusion: The research demonstrated that NOTCH1 showed significant upregulation in oral squamous cell carcinoma and was associated with both immune suppression and unfavorable clinical outcomes. The investigation indicated that NOTCH1 stood as an effective biomarker and therapeutic target for oral cancer.

Keywords: immunity; mucoepidermoid carcinoma; notch1; oral carcinoma; pathways; regulatory; squamous cell.

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Conflict of interest statement

Human subjects: Informed consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Review Board of University of the Punjab issued approval #149-01-2022. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

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