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Antiapoptotic PON2 expression and its clinical implications in locally advanced oral squamous cell carcinoma
Mehta Vedant Kamal1, Rama Rao Damerla2, Preetiparna Parida2
1Department of Surgical Oncology, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Abstract:
Locally advanced oral squamous cell carcinoma poses a significant challenge in oncology due to its rising incidence and mortality rates. Despite therapeutic progress, understanding molecular intricacies is essential. This study explored the role of PON2, a multifunctional enzyme implicated in antiapoptotic mechanisms. Aberrant PON2 expression in oral cancers raises questions regarding its involvement in evading programmed cell death and treatment resistance. Patients with locally advanced disease were enrolled, and molecular analyses were undertaken on the collected tumor and normal tissues. Utilizing computational datasets, this study used in silico gene expression analysis, differential gene expression analysis in our patient cohort, survival analysis, and gene set enrichment analysis to unravel role of PON2 in disease prognosis. The results showed elevated PON2 levels in advanced tumor stages, correlating with factors such as tobacco exposure, higher tumor grade, and nodal metastasis. Survival analysis revealed prognostic relevance of PON2, with lower expression linked to extended survival rates. Gene set enrichment analysis identified pathways aiding in cancer metastasis influenced by PON2. This study underscores the significance of PON2 expression as a prognostic marker for oral malignancies, with increased expression associated with advanced disease stages. Understanding the molecular profile of the PON2 gene suggests its potential as a valuable biomarker for the management of cancer.
Insights
Paranoma or Ocular 2 (PON2) is elevated in advanced oral squamous cell carcinoma, correlating with poor prognosis. Lower PON2 expression indicates better survival, suggesting PON2 as a prognostic biomarker for oral cancer management.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Locally advanced oral squamous cell carcinoma (OSCC) presents a significant clinical challenge with increasing incidence and mortality.
- Understanding the molecular mechanisms underlying OSCC progression, including resistance to apoptosis and treatment, is crucial for improving patient outcomes.
- The paraoxonase 2 (PON2) enzyme, involved in antiapoptotic processes, has shown aberrant expression in various cancers, prompting investigation into its role in OSCC.
Purpose of the Study:
- To investigate the role of PON2 expression in locally advanced oral squamous cell carcinoma.
- To determine the correlation between PON2 levels and clinicopathological features, including tobacco exposure, tumor grade, and nodal metastasis.
- To evaluate the prognostic significance of PON2 expression in OSCC patient survival and identify associated molecular pathways.
Main Methods:
- In silico gene expression analysis using computational datasets.
- Differential gene expression analysis in a cohort of OSCC patients.
- Survival analysis to assess the prognostic value of PON2.
- Gene set enrichment analysis (GSEA) to identify PON2-associated molecular pathways.
Main Results:
- Elevated PON2 expression was observed in advanced OSCC stages.
- Higher PON2 levels correlated with tobacco exposure, increased tumor grade, and lymph node metastasis.
- Survival analysis indicated that lower PON2 expression was associated with significantly longer patient survival.
- GSEA revealed that PON2 influences pathways involved in cancer metastasis.
Conclusions:
- PON2 expression is a significant prognostic marker in oral squamous cell carcinoma.
- Increased PON2 levels are linked to advanced disease stages and poorer prognosis in OSCC.
- The molecular profile of PON2 suggests its potential utility as a biomarker for managing oral cancer.
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