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ARTICLE

miR-449a: A Novel Biomarker for Diagnosis, Prognosis, and Treatment Response in Locally Advanced Laryngeal Squamous Cell Carcinoma

Amal F. Gharib1, Ohud Alsalmi1, Hayaa M. Alhuthali1, Afaf Alharthi1, Saud Ayed Alharthi2, Shaimaa A. Alharthi3, Rasha L. Etewa4, Wael H. Elsawy5,*
1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia
2 Department of Otorhinolaryngology, King Abdulaziz Specialized Hospital, Taif, 26521, Saudi Arabia
3 Department of Medicine, Fakeeh College for Medical Sciences, P.O. Box 2537, Jeddah, 21461, Saudi Arabia
4 Pathology Department, College of Medicine, Jouf University, Sakaka, 72388, Saudi Arabia
5 Clinical Oncology Department, Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt
* Corresponding Author: Wael H. Elsawy. Email: email, email
(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))

Oncology Research https://doi.org/10.32604/or.2025.073051

Received 09 September 2025; Accepted 29 October 2025; Published online 18 December 2025

Abstract

Background: Locally advanced laryngeal squamous cell carcinoma (LA-LSCC) presents clinical challenges due to the lack of reliable non-invasive biomarkers. This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC. Methods: miR-449a expression was analyzed in tumor tissues, adjacent normal tissues, and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). We assessed the diagnostic accuracy by Receiver Operating Characteristic curve (ROC curves), clinicopathological associations, survival outcomes (Kaplan-Meier), and treatment response dynamics. Results: miR-449a was significantly downregulated in LA-LSCC tissues (p < 0.0001) and serum (p < 0.0001), with a strong tissue-serum correlation (R2 = 0.988). Tissue miR-449a demonstrated a diagnostic accuracy (Area Under the Curve, AUC = 0.857), while serum showed moderate accuracy (AUC = 0.734). High miR-449a expression correlated with favorable clinicopathological features and improved survival (median overall survival: 67.82 vs. 23.74 months; p = 0.0012). Multivariate analysis confirmed miR-449a as an independent prognostic factor (p < 0.001). miR-449a levels increased post-treatment, particularly in responders to chemotherapy/radiation (p < 0.0001). Conclusion: miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis, prognosis, and treatment monitoring. Its dynamic expression highlights potential for risk stratification and therapy response prediction, warranting further validation in larger cohorts.

Keywords

Locally advanced laryngeal squamous cell carcinoma (LA-LSCC); microRNA-449a (miR-449a); biomarker; prognosis; diagnosis; treatment response; serum biomarker; chemoradiotherapy; organ preservation

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