Tehran University of Medical Sciences Journal of Craniomaxillofacial Research 2345-5489 13 3 2026 10 24 360 364 Monireh Kiaghadi Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran; Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran. Mohammad Bayat Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Oral & Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. Hooman Sharifi Tobacco Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Abdolreza Mohammadnia Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Farnoosh Mohammadi Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Oral & Maxillofacial Surgery, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran. Masoume Farhangiyan Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran. Rojin Samani Dental Implant Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Naghmeh Bahrami Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2025 10 19 2025 11 28 Introduction: Oral squamous cell carcinoma is an uncommon and potentially aggressive malignant tumor arising from Oral epithelial remnants. Identification of molecular alterations involved in Oral squamous cell carcinoma may contribute to the discovery of reliable diagnostic and prognostic biomarkers and potential therapeutic targets. PRKAR1A encodes the regulatory subunit type I-alpha of protein kinase A (PKA) and may play an important role in cellular signaling and tumor development. This study aimed to evaluate PRKAR1A gene expression in peripheral blood samples from patients with Oral squamous cell carcinoma compared with healthy individuals and to investigate its association with clinicopathological characteristics of the disease.  Materials and Methods: In this case-control study, peripheral venous blood samples were collected from 30 patients with histopathologically confirmed Oral squamous cell carcinoma and 30 healthy individuals matched for age and sex. Total RNA was extracted from blood samples using the Viva 2-Step RNA extraction method. Following reverse transcription, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine PRKAR1A mRNA expression. GAPDH was used as the internal reference gene, and relative gene expression was calculated using the 2^−ΔΔCt method. Statistical analyses were selected according to the distribution and type of the variables. Independent-samples t-test or Mann–Whitney U test was used for comparison between the two study groups, as appropriate. Associations between PRKAR1A expression and clinicopathological characteristics were evaluated using appropriate parametric and non-parametric tests.  Results: PRKAR1A mRNA expression was significantly lower in peripheral blood samples from patients with Oral squamous cell carcinoma compared with healthy controls (P < 0.05). Reduced PRKAR1A expression was also associated with more advanced tumor stage, poorer histological grade, and the presence of metastasis (P < 0.05).  Conclusion: The findings suggest that reduced PRKAR1A expression in peripheral blood may be associated with Oral squamous cell carcinoma and with clinicopathological indicators of tumor progression. PRKAR1A may have potential as a molecular biomarker of Oral squamous cell carcinoma. However, the relatively small sample size and absence of HPV assessment should be considered when interpreting these findings. Larger, adequately powered studies are required to validate the diagnostic and prognostic value of PRKAR1A in Oral squamous cell carcinoma.  Keywords: PRKAR1A; Oral squamous cell carcinoma; Gene expression; PKA signaling. https://jcr.tums.ac.ir/index.php/jcr/article/view/571 https://jcr.tums.ac.ir/index.php/jcr/article/download/571/517