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 cut-off 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.

Cellular Concentration of Survivin and Caspase 3 in Habitual Tobacco Chewers with and without Oral Squamous Cell Carcinoma in South Indian Rural Population-A Case Control Study.

Background: There is paucity of data on tissue levels of Survivin and Caspase 3 in south Indian tobacco chewers with oral Squamous cell carcinoma (OSCC). Oral cancer is a rapidly growing, highly prevalent head and neck malignancy; it involves a mucosal epithelium of a buccal cavity exposed to tobacco and other carcinogens. The basis of the survival of a tumor cell or transformed normal cell into a neoplastic cell is by the suppression of apoptosis regulation. Recently, researchers have focused on Survivin, an inhibitor of apoptosis family of proteins (IAP), involved in apoptosis regulation in cancer cells targeting the executioner Caspase 3. The current study aims to quantify the cellular levels of Survivin and Caspase 3 in tobacco chewers with OSCC and in habitual tobacco chewers without OSCC, in comparison to controls. Methods: A single centric case control study included 186 study subjects, categorized into: Group I (n = 63), habitual tobacco chewers with OSCC; Group 2 (n = 63), habitual tobacco chewers without OSCC; and Group 3 (n = 63), the controls. Resected tumor tissue from Group 1 and buccal cell samples from Groups 2 and 3 were collected into phosphate buffer saline (PBS) and assayed for Survivin and Caspase 3 levels by the ELISA sandwich method. 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. 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.

Usefulness of salivary sialic acid as a tumor marker in tobacco chewers with oral cancer.

AIM: This study aims to assess the usefulness of salivary sialic acid (SA) as a tumor marker in the detection of oral squamous cell carcinoma (OSCC) among tobacco chewers. MATERIALS AND METHODS: After the approval of study protocol by the Institutional Ethics Committee and informed voluntary consent, salivary samples were collected from 96 participants in each group of tobacco chewers with OSCC, tobacco chewers without precancerous or cancerous lesion, and healthy controls. Salivary protein-bound SA (PBSA) and salivary-free SA (FSA) were measured by Yao et al.'s method of acid ninhydrin reaction, and the data were subjected to appropriate statistical analysis. RESULTS: The salivary PBSA and FSA levels in the Groups 1, 2, and 3 participants were 31.17 ± 7.6 mg/dL and 63.45 ± 9.8 mg/dL, 25.45 ± 16.61 mg/dL and 33.18 ± 11.38 mg/dL, and 22.73 ± 3.01 mg/dL and 21.62 ± 8.86 mg/dL, respectively. Salivary FSA levels were significantly increased among the tobacco chewers with OSCC patients (Group 1) and tobacco chewers with no premalignant lesions of the oral cavity (Group 2) compared to the healthy controls (Group 3) with P < 0.05 being statistically significant. Salivary FSA levels were significantly increased in Group 1 as compared with Group 2. The salivary PBSA was high among Group 1 as compared to the control Group 3; there was however no significant difference in the levels of salivary PBSA between Group 1 and Group 2. There was no significant difference in the PBSA levels between OSCC patients of Group 1 and the tobacco chewers without precancerous or cancerous lesion in the oral cavity of Group 2. CONCLUSION: Salivary PBSA and FSA are significantly raised in both tobacco chewers with OSCC and in tobacco chewers with no precancerous or cancerous lesions in the oral cavity. SA should therefore be used cautiously while considering it as a marker for the early detection of oral cancer. Tobacco can be a crucial confounding factor when SA is used as a biomarker in OSCC since their levels are elevated to some extent even in tobacco chewers without any clinically obvious precancerous or cancerous lesions in the oral cavity.