Evaluation of MDM2 mRNA expression according to clinicopathological characteristics in patients with oral squamous cell carcinoma

Aliffala  Widianaputri Setya Pangastuti; Nabella  Deby Ramadhani; Kurnia  Jelang Ramadian; Choirum  Minannisa Imma Mahardika; A  Haris Budi Widodo; Dody  Novrial; Daniel  Joko Wahyono; Tirta  Wardana

Authors

Aliffala Widianaputri Setya Pangastuti Dental Medicine, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia
Nabella Deby Ramadhani Dental Medicine, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia
Kurnia Jelang Ramadian Dental Medicine, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia
Choirum Minannisa Imma Mahardika Dental Medicine, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia
A Haris Budi Widodo Dental Medicine, Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia
Dody Novrial Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia
Daniel Joko Wahyono Faculty of Biology, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia
Tirta Wardana Faculty of Medicine, Jenderal Soedirman University, Purwokerto, Central Java, Indonesia

Keywords:

Livak’s method, MDM2 mRNA, oral cancer, OSCC, real-time qPCR

Abstract

Background: The murine double minute 2 (MDM2) gene encodes an E3 ubiquitin ligase that targets p53 for degradation, which influences the pathogenesis of oral squamous cell carcinoma (OSCC).

Objective. This study determined MDM2 mRNA expression and evaluated its association with the clinical and pathological characteristics thereof in patients with OSCC.

Methods: We performed an observational–analytical study using a cross-sectional design involving 39 patients with OSCC. RNA extraction, complementary DNA synthesis, and quantitative real-time polymerase chain reaction were performed. The relative MDM2 mRNA expression was quantified using the Livak method (2-ΔΔCT) with GenEX MultiD software version 6.0. Statistical significance was assessed using unpaired Student t-tests.

Results: MDM2 mRNA expression was 1.64-fold lower in patients with OSCC and tumor volumes >5 cc compared with those ≤ 5 cc (CT mean ± SE: 32.0 ± 2.6vs. 32.7 ± 1.8, respectively; P = 0.34). In high-grade cases, the expression was 0.92-fold lower than in low-grade cases (32.1 ± 2.3 vs. 32.2 ± 2.7, respectively; P = 0.90). The expression thereof was also 2.12-fold higher in smokers than in non-smokers (31.8 ± 2.4 vs. 32.9 ± 2.1, respectively; P = 0.3). None of these differences were significant. Network analysis identified MDM2, TP53, and CDKN1A as central hub genes, thus bridging p53 signaling, cell cycle regulation, and cellular senescence in OSCC. Gene Ontology enrichment revealed significant overrepresentation of p53-mediated DNA damage response and apoptotic pathways among the candidate genes.

Conclusion: Although MDM2 mRNA expression exhibited no significant clinical associations, in silico profiling identified MDM2 as a central molecular hub linking p53 signaling and cell cycle regulation in OSCC, thereby suggesting a mechanistic role that warrants further functional validation.

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