Title : Survivin and its splicing isoforms gene expression in oral squamous cell carcinoma patients
Abstract:
Background: Oral squamous cell carcinoma (OSCC) has become a major oncologic problem. Survivin overexpression in OSCC could be associated with increased aggressiveness, poor response to chemotherapy and prediction of patient survival. This study was conducted to analyze the mRNA expression of Survivin and its splicing isoforms in OSCC patients.
Materials and methods: This was cross-sectional analytical study during 2022-2024. Thirty histologically proven newly diagnosed OSCC patients came to University of Dental Medicine, Mandalay were collected. Clinical tumor and nodal stages were verified by contrast-enchanced computed topography. Histopathological grading were confirmed by Bryne's grading system. Primary tumor tissues and adjacent normal oral mucosa from the same patients were collected, preserved in RNAlater at -80oC freezer and analysed determinination of mRNA level of Survivin and its 4 isoforms (2α, 2B, 3B and ΔEx3) by semi-quantitative reverse transcription-polymerase
chain reaction (qRT-PCR).
Results: The highest frequency age group for OSCC was 41- 60 years (53%). Male and female ration was 2.3:1. Total 24/30, 80% were low grade and 6/30 cases (20%), high grade. The expression of ΔEx3 was the highest level (mean Ct = 34.57) followed by 3B (34.54), Survivin (32.01) and 2α (31.82) in OSCC tissues. The differences of the mRNA expression of Survivin and its splicing isoforms between normal mucosa and OSCC tissues resected from OSCC patients were statistically significant (p<0.05). There were statistically significant upregulation of the expression of Survivin, 3B and ΔEx3 in advanced stage (p<0.05) and 2α was significantly more upregulated in early staged compared to advanced stage (p<0.05). There were not statistically significant difference in the expression of Survivin and its isoforms in relation to Bryne’s Grading System among OSCC patients (p>0.05). The Survivin, 2α, 3B and ΔEx3 isoform was significantly overexpressed among tumor areas compared to normal tissue in 87%, 57%, 77% and 93% of OSCC with fold changes of 3.01, 1.74, 4.55 and 4.01 (2-ΔΔCt) relative units respectively (p<0.05).
Conclusion: Survivin and its splicing isoforms are highly expressed in OSCC and expression of different level of isoforms play an important role in tumor aggressiveness and predict the prognosis of OSCC by implying with clinical staging and histopathological grading in OSCC.
Keywords: OSCC, Oral Squamous Cell Carcinoma, Bryne’s grading, Survivin, RT-PCR.