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

Abstract

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.

Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics

“…Herein, we constructed a nanosystem consisting of aptamer-modified artificial vesicles, hMNs, and two gene therapy agents DNAzymes for RB-targeted fluorescence/magnetic resonance (FL/MR) dual-modality imaging and dual gene silencing therapy (Scheme ). In this study, two DNAzymes were used as gene therapy agents to overcome the limited effect of single gene therapy, targeting RB antiapoptotic factors Bcl-2 and Svv mRNA for simultaneous silencing and synergistic stimulation of apoptosis . The hMNs nanocarrier was GSH sensitive, which simultaneously acted as a precursor of DNAzyme cofactor and quencher of fluorophore-modified DNAzymes, facilitating intracellular DNAzyme catalysis and FL/MR imaging analysis .…”

“…In this study, two DNAzymes were used as gene therapy agents to overcome the limited effect of single gene therapy, targeting RB antiapoptotic factors Bcl-2 and Svv mRNA for simultaneous silencing and synergistic stimulation of apoptosis. 44 The hMNs nanocarrier was GSH sensitive, which simultaneously acted as a precursor of DNAzyme cofactor and quencher of fluorophore-modified DNAzymes, 45 facilitating intracellular DNAzyme catalysis and FL/MR imaging analysis. 46 For enhancing the biocompatibility and stability in vivo of DNAzymes and hMNs composite nanoparticles (Dual/hMNs), an EG-derived artificial vesicle was applied to wrap Dual/hMNs to form EG@Dual/hMNs.…”

Identification of prognostic biomarkers of smoking-related lung cancer

“…Studies have found that nicotine, a major component of tobacco, can affect the expression of the Bcl-2 family proteins in lung cancer cells, promoting cancer cell growth and enhancing drug resistance ( 10 , 11 ). Tobacco activates the Notch signaling pathway to induce lung cancer and regulates cell apoptosis by increasing survivin expression, thereby promoting the malignant transformation of bronchial epithelial cells ( 12 ). Vellichirammal et al reported a positive correlation between smoking and fusion frequency in lung adenocarcinoma and found that as a fusion gene associated with cigarette smoke exposure, downregulation of the P53 pathway resulted in higher gene fusion formation in lung adenocarcinoma ( 13 ).…”