An Insight into Survivin in Relevance to Hematological, Biochemical and Genetic Characteristics in Tobacco Chewers with Oral Squamous Cell Carcinoma

Background: Survivin is an inhibitor of apoptosis protein (IAP), encoded by the Baculoviral IAP Repeat Containing 5 (BIRC5) gene located on q arm (25.3) on chromosome 17. It is expressed in various human cancers and involved in tumor resistance to radiation and chemotherapy. The genetic analysis of the BIRC5 gene and its protein survivin levels in buccal tissue related to oral squamous cell carcinoma (OSCC) in South Indian tobacco chewers has not been studied. Hence, the study was designed to quantify survivin in buccal tissue and its association with pretreatment hematological parameters and to analyze the BIRC5 gene sequence. Method: In a single centric case control study, buccal tissue survivin levels were measured by ELISA. A total of 189 study subjects were categorized into Group 1 (n = 63) habitual tobacco chewers with OSCC, Group 2 (n = 63) habitual tobacco chewers without OSCC, and Group 3 (n = 63) healthy subjects as control. Retrospective hematological data were collected from Group 1 subjects and statistically analyzed. The BIRC5 gene was sequenced and data were analyzed using a bioinformatics tool. Results: Survivin protein mean +/- SD 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 significance (p < 0.001). 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 unique variants found only in OSCC patients 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. Conclusions: The tissue survivin level increased in OSCC patients compared to controls; pretreatment AMC, LMR, and NLR may serve as add-on markers along with survivin to measure the progression of OSCC. Unique mutations in the promoter and exons 3-5 were observed in sequence analysis and were associated with survivin concentrations.

Automated summary

This study aimed to investigate the levels of survivin in buccal tissue of South Indian tobacco chewers and its association with pretreatment hematological parameters, as well as analyze the sequence of the BIRC5 gene. The results showed that survivin levels were significantly higher in tobacco chewers with oral squamous cell carcinoma (OSCC) compared to healthy subjects, and levels of absolute monocyte count (AMC), neutrophil/lymphocyte ratio (NLR), and lymphocyte/monocyte ratio (LMR) were also significantly correlated with survivin levels. Sequence analysis of the BIRC5 gene identified unique mutations associated with survivin concentrations.