Characterization of DJ-1, PTEN, and p-Akt as Prognostic Biomarkers in the Progression of Oral Squamous Cell Carcinoma

Mourad Kerdjoudj; Rey A De La Torre; Hilal Arnouk

doi:10.7759/cureus.34436

Characterization of DJ-1, PTEN, and p-Akt as Prognostic Biomarkers in the Progression of Oral Squamous Cell Carcinoma

Cureus. 2023 Jan 31;15(1):e34436. doi: 10.7759/cureus.34436. eCollection 2023 Jan.

Authors

Mourad Kerdjoudj¹, Rey A De La Torre², Hilal Arnouk^{3

4

5

6

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Affiliations

¹ Internal Medicine, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, USA.
² Osteopathic Medicine, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, USA.
³ Pathology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, USA.
⁴ Pathology, College of Graduate Studies, Midwestern University, Downers Grove, USA.
⁵ Pathology, College of Dental Medicine-Illinois, Midwestern University, Downers Grove, USA.
⁶ Pathology, Chicago College of Optometry, Midwestern University, Downers Grove, USA.
⁷ Molecular Pathology, Precision Medicine Program, Midwestern University, Downers Grove, USA.

Abstract

Objective Oral cancer has a five-year survival rate of 68%, and the methods used to assess it still rely heavily on morphology. Protein biomarkers can potentially increase the predictive power of histopathological evaluation. This study aims to examine the expression of three closely linked proteins implicated in the pathogenesis of oral squamous cell carcinoma (OSCC); protein deglycase (DJ-1), an oncogene, phosphatase, and tensin homolog (PTEN), a tumor suppressor gene, and phosphorylated protein kinase B (p-Akt), the activated form of a vital serine/threonine kinase, which is involved in the oncogenesis of several human malignancies, throughout the tumor progression steps to establish their potential as prognostic biomarkers. Study design Western blot analysis was carried out using four different cell lines representing the successive steps of OSCC progression, including normal oral keratinocytes, dysplastic oral keratinocytes, locally invasive OSCC, and metastatic OSCC. Results DJ-1 expression was found to be upregulated gradually throughout the successive steps of OSCC progression from normal to dysplastic to locally invasive to metastatic OSCC. PTEN expression showed an overall opposite trend. Interestingly, a significant downregulation of p-Akt was seen in the locally invasive OSCC cells, although it was followed by a significant increase in p-Akt expression in the metastatic OSCC cell line, which is consistent with the role of p-Akt in the motility and migration of cancer cells. Conclusion This study documented trends in expression patterns of three important signaling molecules, DJ-1, PTEN, and p-Akt, in normal, premalignant, and malignant oral keratinocytes. The oncogenic DJ-1 and tumor suppressor PTEN were expressed in a manner consistent with their respective roles in tumorigenesis, while p-Akt only showed a significant upregulation in the metastatic OSCC cells. Overall, all three proteins exhibited unique trends throughout the progressive stages of OSCC tumor progression, thereby adding to their potential utility as prognostic biomarkers for oral cancer patients.

Keywords: diagnostic biomarkers; dj-1; head and neck cancer; metastatic cancer; oral epithelial dysplasia; oral squamous cell carcinoma; p-akt; prognostic biomarker; pten; tumor progression.