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Title: | Genetic Analysis of Apoptosis Inhibitor Candidate Gene Birc5 And its Expressed Protein Level in Patients With Oral Squamous Cell Carcinoma in Rural Population |
Authors: | Susanna T Y |
Issue Date: | Aug-2023 |
Publisher: | SDUAHER |
Abstract: | Background: Oral cancer is a rapidly growing, highly prevalent head and neck malignancy involving oral mucosal epithelium exposed to tobacco and other carcinogens. Suppression of apoptosis regulation is one of the hallmarks of survival in transformation of normal into a neoplastic cell. Recently, Survivin protein is targeted by researchers in various types of cancer. Survivin is an inhibitor of apoptosis family of proteins (IAP), linked with apoptosis regulation in cancer cells through its influence on Caspase-3. Survivin encoded by Baculoviral IAP Repeat Containing 5 (BIRC5) gene on 17q25.3. Survivin is predominantly expressed in human cancers than normal cells, and involved in tumour resistance to radiation and chemotherapy drugs. There is a need for the study on Survivin levels and its genetic analysis in tobacco users/chewers with and without Oral Squamous Cell Carcinoma (OSCC) in comparison with non tobacco users/chewers in south Indian rural population. Further, retrospective data on the pre treatment hematological parameters were analysed in with tissue survivin levels in OSCC cases. Methods: Study design was single centeric case control study, consists of total 189 subjects, they were categorized into: Group-1 (n = 63), chronic tobacco chewers with OSCC, Group-2 (n =63), chronic tobacco chewers without OSCC and Group-3 (n =63), the controls. Sample collection: Resected tumour tissue from Group-1 and buccal cell samples from Groups-2 and Groups-3 were collected into phosphate buffer saline (PBS) and assayed for Survivin and Caspase-3 levels by the Enzyme Linked Immunosorbent Assay (ELISA) sandwich method. The pretreatment hematological secondary data of OSCC patients were obtained from the medical records section. The Group-1 hematological data collected was statistically analyzed. In the study subjects, BIRC5 gene promoter and exons were sequenced and the data obtained was analysed using bioinformatics tool. XVI Results: The mean ± SD of the Survivin protein in Group-1 was (1670.9 ± 796.21 pg/mL), in Group-2, it was (1096.02 ± 346.17 pg/mL), and in Group-3, it was (397.5 ± 96.1 pg/mL) with a significance of p< 0.001. Similarly, the level of Caspase-3 in Group-1 was (7.48 ± 2.67 ng/mL), in Group-2, it was (8.85 ± 2.41 ng/mL), and in Group-3, it was (2.27 ± 2.24 ng/mL) with a significance of p <0.001. In the current study, the cut-off value of survivin levels determined in controls was 457 pg/mL, whereas in case of tobacco chewers without OSCC was 1244.84 pg/mL, survivin levels above the cut off value indicates high risk for OSCC.The Odds ratio determined was 4.397 between Group (1&2) and 69.6 between Group (1&3). Survivin levels showed significance with cutoff levels of Absolute monocyte count (AMC), Neutrophil/Lymphocyte ratio (NLR), and Lymphocyte/Monocyte ratio (LMR) at (p = 0.001). The the unique variants found only in OSCC patients in BIRC5 gene sequence data were T→G in the promoter region, G→C in Exon 3, C→A, A→G, G→T, T→G, A→C, G→A in Exon 4, C→A, G→T, G→C in the Exon 5 region. Conclusion: The progressive transformation of buccal cells to neoplastic cells is evident, in the case of OSCC, this indicates that the over-expression of Survivin compared to Caspase-3 confirms the suppression and dysregulation of apoptosis, Pretreatment AMC, LMR, and NLR may serve as add-on markers along with survivin to measure the progression of OSCC, unique mutations and their effects on survivin protein is observed in OSCC patients. |
URI: | http://172.16.4.202:8080/xmlui/handle/123456789/8521 |
Appears in Collections: | Cell Biology & Molecular Genetics |
Files in This Item:
File | Description | Size | Format | |
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Susanna T Y_CBMG.pdf | 7.04 MB | Adobe PDF | View/Open |
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