Up-regulation of extracellular-matrix and inflammation related genes in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy with late-presentation, site-specific heterogeneity, and high-propensity for recurrence/metastasis that has shown rise in mortality. Lately, research emphasize on dynamic interactions between tumor-cells and extracellular-matrix components within tumor-microenvironment that promote tissue integrity loss and carcinogenesis. Therefore, OSCC clinical-management is still challenging. DESIGN: Present study validated clinical utility of a 13 gene-panel in two chief sub-sites of OSCC: Buccal mucosa squamous cell carcinoma (BMSCC) (N = 50) and Tongue squamous cell carcinoma (TSCC) (N = 52) using qRT-PCR. Principal component analysis and binary logistic regression analysis were applied to acquire definite multi gene models. Protein expression analysis was employed using the Human Protein Atlas, UALCAN and TIMER 2.0 databases to explore potential correlation between immune cells and gene-panels. RESULTS: Significant up-regulation of CXCL8, CXCL10, FN1, GBP1, IFIT3, ISG15, MMP1, MMP3, MMP10, PLAU, SERPINE1 and SPP1 except OASL was observed in OSCC tissue in comparison of absolute normal controls. Although, this gene-panel could potentially discriminate OSCC tissues from absolute normal controls as solitarily diagnostic and/or predictive biomarkers, models generated also showed substantial discriminating efficacy. Eight-genes were found to be significantly associated with poor-prognosis on clinico-pathological association. Protein-expression confirmed overexpression of gene-panel and added advantage of being secretory-protein. Importantly, up-regulated genes in our study showed significant relation with immune-cells infiltration suggesting their contribution in immune-escape. CONCLUSION: Thus, we propose that the 13 gene-panel could pave the way to effective and personalized clinical-management of OSCC in terms of diagnostic and prognostic measures and thereby as therapeutic targets.

Association of vitamin D receptor gene polymorphisms with breast cancer risk.

BACKGROUND: Recent literature suggests that vitamin D signaling has a protective effect against breast cancer risk. Thus, the aim of the present study was to find the association of vitamin D receptor (VDR) gene polymorphisms with breast cancer risk. MATERIALS AND METHODS: Fok1, Bsm1, Apa1, and Taq1 polymorphisms were performed by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) method, and Poly A polymorphism was carried out using PCR-SSCP in 140 breast cancer patients and 155 controls. RESULTS: Odds ratio was significantly higher in both homozygous variant genotypes (LL) of Poly A polymorphism of VDR (odds ratio [OR] = 5.42, 95% confidence interval [CI] = 1.19-23.31, P = 0.02) and heterozygous variant genotypes (SL) of Poly A polymorphism of VDR (OR = 3.89, 95% CI = 1.10-13.7, P = 0.03). Fok1, Bsm1, Apa1, and Taq1 polymorphisms of VDR gene were not significantly associated with breast cancer risk. CONCLUSION: Poly A polymorphism at the 3' untranslated region (UTR) of VDR gene was significantly associated with breast cancer risk in West Indian population.

An integrative analysis to enumerate candidate genes for clinical use in oral cancer.

Background: Oral cancer (OC) is the most pernicious sub-site of head and neck tumours with poor prognostic value that is largely ascribed to the lack of ideal biomarkers and therapeutic targets. This fact highlights an urgent need to identify biomarkers that can further aid in OC management. Aim: The aim of this study was to identify a gene panel with a maximum clinical utility for OC. Materials and Methods: Eight eligible datasets were downloaded from the Gene Expression Omnibus Database, containing 320OC samples and 173 normal samples. The data were processed by GeneSpring software to reveal differentially expressed genes between OC tissues and normal tissues in eight individual experiments. Functional enrichment and network analysis were performed using PANTHER and STRING databases for concordant genes (fold change >10; P ≤ 0.05). The selected genes were cross-validated in the cancer genome atlas (TCGA), Oncomine, and KaplanMeier (KM) plotter databases. Results: Totally, 65 concordant genes were identified, including 37 up-regulated genes and 28 down-regulated genes. A 13-gene panel CXCL8, CXCL10, FN1, GBP1, IFIT3, ISG15, MMP1, MMP3, MMP10, OASL, SERPINE1, SPP1, and PLAU was elected from the lists of functionally enriched genes, hub genes, and genes that showed high alterations for mutation, copy number variation, and mRNA expression status in 'Head and Neck Squamous Cell Carcinoma patients (n = 279; TCGA, Nature 2015)'. Further, validation in Oncomine database demonstrated significant over-expression of all elected genes in OC patients across multiple datasets. In addition, out of 13, six genes (CXCL8, CXCL10, FN1, PLAU, SERPINE1, and SPP1) showed significant association with the prognosis of Head and Neck cancer patients (n = 500) in the KM plotter database. Conclusions: Using an integrative analysis, our study investigated and validated a 13-gene panel for OC which can be used to improve current diagnostic, prognostic, and treatment approaches.

Alterations in Sialylation Patterns are Significantly Associated with Imatinib Mesylate Resistance in Chronic Myeloid Leukemia.

BACKGROUND AND AIM: The study examined sialylation changes for their potential predictive value in assessment of imatinib mesylate (IM) resistance, alone and/or with BCR-ABL1 transcript variants among chronic myeloid leukemia (CML) cases. METHODS: A total of 98 CML cases (un-treated cases, IM non-responders and IM responders) were enrolled in the study. Total sialic acid (TSA) and total protein (TP) levels were estimated spectrophotometrically, the expression profiles of BCR-ABL1, ST3GAL1 and ST3GAL2 were evaluated using qRT-PCR assays and BCR-ABL1 transcript variants were identified through subjecting PCR products to agarose gel electrophoresis. RESULTS: The results manifested increase in e14a2 transcript and decrease in co-expression of both transcripts (e13a2 and e14a2) in IM non-responders than un-treated CML cases. Notably, TSA/TP ratio was higher, whereas ST3GAL1 and ST3GAL2 expressions were lower in un-treated CML cases and IM non-responders as against IM responders. Further, ST3GAL2 expression was lower in un-treated CML cases than IM non-responders. Receiver operating characteristic curves also proved their discriminatory efficiencies. Decisively, the rise in TSA levels and the fall in ST3GAL1 and ST3GAL2 levels were evidently related to CML progression and clinical indicators of treatment failure (high BCR-ABL1 ratio, high WBC count, high platelet count and low Hb levels). The alterations in TSA, ST3GAL1 and ST3GAL2 levels were remarkably associated with each other. CONCLUSIONS: The altered levels of TSA, ST3GAL1 and ST3GAL2 are, to a significant extent, associated with IM resistance in CML, which have clinical relevance in treatment monitoring and IM resistance treatment.

Transcriptional Biomarkers in Oral Cancer: An Integrative Analysis and the Cancer Genome Atlas Validation.

OBJECTIVE: An impervious mortality rate in oral cancer (OC) to a certain extent explains the exigencies of precise biomarkers. Therefore, the study was intended to identify OC candidate biomarkers using samples of healthy normal tissues (N=335), adjacent normal tissues (N=93) and OC tissues (N=533) from online microarray data. METHODS: Differentially expressed genes (DEGs) were recognised through GeneSpring software (Fold change >4.0 and 'p' value.

Apoptosis stimulating protein of p53 (ASPP) 1 and ASPP2 m-RNA expression in oral cancer.

OBJECTIVE: The present study was carried out to unfold the clinical significance of apoptosis stimulating protein of p53 (ASPP) 1 and ASPP2 expression in oral cancer (OC). METHODS: Tissue specimens (malignant and their corresponding adjacent normal) from 40 pathologically confirmed OC patients treated at the Institute were included in the study. ASPP1 and ASPP2 expression were examined using semi-quantitative RT-PCR. RESULTS: The results indicated lower ASPP1 expression in OC tissues as compared to adjacent normal tissues (p = 0.085). Stratified analysis as per tumor site revealed significant down-regulation of ASPP1 in tongue cancer tissues (p = 0.005). Receiver operating characteristic curve depicted significant discriminatory efficacy in distinguishing tongue cancer tissues and adjacent normal tissues (p = 0.019). Moreover, ASPP1 expression was remarkably declined in stage II, III and IV OC tumors than stage I OC tumors (p = 0.007, 0.092 and 0.013, respectively). A similar trend was observed in buccal mucosa tumors on further analysis. ASPP2 expression was lower in moderately differentiated OC tumors as compared to well differentiated OC tumors (p = 0.061). Significantly reduced ASPP2 expression was observed in tongue cancer tumors without invasion in contrast to tumors with perineural invasion (p = 0.007). Besides, ASPP1 and ASPP2 expression was positively inter-correlated in tongue tissues (r = 0.325, p = 0.091). CONCLUSIONS: Lower ASPP1 expression in tongue cancer during malignant transformation has significance in cancer initiation. Association of reduced ASPP1 and ASPP2 expression with advanced disease stage and moderate differentiation suggests their role in OC progression. Thus, down-regulation of ASPP1 and ASPP2 may serve as potential diagnostic and prognostic indicators in OC.

Clinical significance of serum 25 hydroxyvitamin D in breast cancer: An Indian scenario.

Recent evidences suggest a protective mechanism of vitamin D signaling against breast cancer by the autocrine/paracrine manner and may modestly reduce the risk of breast cancer. Despite lots of sunshine, vitamin D deficiency is widespread in India. Moreover, there are limited studies from Indian population regarding circulatory 25(OH) D and breast cancer risk. Thus, the aim of the present study is to investigate circulatory 25(OH) D in relation to breast cancer risk and its association with various clinico-pathological parameters from Indian population. Total 297 subjects, comprising of 157 controls and 140 breast cancer patients were enrolled for the study. Circulatory 25(OH) D was analyzed by HPLC. Statistical analysis was carried out by SPSS software version 15. Further, subjects were categorized into severe, moderate, mild vitamin D deficiency and sufficiency. The prevalence of severe and moderate 25(OH) D deficiency was higher in breast cancer patients as compared to controls. Mean values of 25(OH) D were lower in breast cancer patients as compared to controls in mild, moderate and severe deficient groups (p = 0.07, p = 0.003 and p = 0.001). Moreover, 25(OH) D was significantly lower in postmenopausal breast cancer patients as compared to premenopausal breast cancer patients, particularly in severe deficient group. The levels of 25(OH) D were lower in ER and PR negative receptor status as compared to the positive receptor in severe deficient category (p = 0.06 and p = 0.09 respectively). Whereas, the mean values of 25(OH) D were lower in HER 2 negative receptor status as compared to positive receptor status in the moderate deficient category (p = 0.09). Further, severe deficient group showed significantly lower levels of 25(OH) Din TNBC as compared to luminal A subtype (p = 0.01). Thus, Results indicate that 25(OH) D deficiency might be associated with increased risk of breast cancer. Moreover, severe 25(OH) D deficiency is associated with aggressive behavior of breast cancer.

Transcriptome profiling and pathway analysis in squamous cell carcinoma of buccal mucosa.

BACKGROUND: High recurrence and poor overall survival in buccal mucosa squamous cell carcinoma (BMSCC) are not well addressed due to lack of efficient prognostic biomarkers and targeted therapies. To uncover gene candidates for the same, transcriptome profiling has been examined in BMSCC, which is not explored yet. METHODS: We compared 9 BMSCC and 2 normal oral FFPE tissues using Agilent SurePrint G3 Human gene expression v3 microarray chips. The obtained RNA signatures were interrogated in the cancer genome atlas (TCGA) dataset for alteration values and survival data. RESULTS: We found total 237 protein coding RNAs and 85 long non-coding RNAs (lncRNAs) which displayed significant differential expression with criteria of at-least 2 fold change and Benjamini Hochberg FDR < .05. In protein coding RNAs, RUNX3 and EMX2 showed utmost degree of up-regulation and down-regulation, respectively. Likewise, among lncRNAs, ARGFXP2 and lnc-SYCP3-2 displayed highest degree of up-regulation and down-regulation, respectively. Besides, an analysis of the RNA list in TCGA dataset spotted deregulation of 21 genes in both, our cohort and TCGA cohort. Among which, MRTO4 and EIF3J genes, and LINC00310, a lncRNA showed greatest expression alterations. Strikingly, at RNA expression level, up-regulation of two genes, EIF3J and SDCBP, was significantly associated with disease free survival and poor overall survival, respectively. CONCLUSION: Our data documented significant findings to enhance understanding of the disease biology. The proposed RNA candidates (RUNX3, EMX2, MRTO4, EIF3J, SDCBP and LINC00310) may serve as putative therapeutic targets and potential biomarkers for BMSCC diagnosis and prognosis.

Determination of normal maxillary transverse dimension by using intercanine width and interpalatal first molar width.

BACKGROUND: Malocclusion in the vertical and sagittal planes is easy to observe whereas it is difficult to diagnose malocclusion in the transverse plane. There are yet no criteria defining a normal transverse occlusion. AIM: The aim of this study was to identify a ratio that defines a normal transverse occlusion. STUDY DESIGN: This was a retrospective study. MATERIALS AND METHODS: A total sample of 151 maxillary dental models (M = 55, F = 96) in the age range of 12-16 years were randomly selected, with 73 models in control group and 78 in the study group. All the models were mixed up and given to an operator for the measurement of intercanine width (ICW) and inter-palatal molar width (IPMW). STATISTICAL ANALYSIS USED: The data were statistically analyzed using SPSS software version 16.0. Chi-square test was performed to test the statistical significance difference between the groups at p ≤ 0.05. RESULTS: Nearly 98.60% of normal arches were found to have an IPMW to ICW ratio of 1:1 ± 0.05. On further analysis, it was found that when IPMW ≥37.45 mm, then the case may be considered to have normal arches, and if the ratio between IPMW to ICW is 1.15:1 ± 0.05 or more and IPMW is <34.92 mm, then the case may be identified as deficient arch. CONCLUSION: The IPMW-to-ICW ratio can be used to differentiate deficient and normal arches. This hypothesis (Banker's hypothesis) is an easy and noninvasive method, using only two parameters, developed to help clinicians in identifying normal transverse dimension.

Recent candidate molecular markers: vitamin D signaling and apoptosis specific regulator of p53 (ASPP) in breast cancer.

Regardless of advances in treatment modalities with the invention of newer therapies, breast cancer remains a major health problem with respect to its diagnosis, treatment and management. This female malignancy with its tremendous heterogeneous nature is linked to high incidence and mortality rates, especially in developing region of the world. It is the malignancy composed of distinct biological subtypes with diverse clinical, pathological, molecular and genetic features as well as different therapeutic responsiveness and outcomes. This inconsistency can be partially overcome by finding novel molecular markers with biological significance. In recent years, newer technologies help us to indentify distinct biomarkers and increase our understanding of the molecular basis of breast cancer. However, certain issues need to be resolved that limit the application of gene expression profiling to current clinical practice. Despite the complex nature of gene expression patterns of cDNAs in microarrays, there are some innovative regulatory molecules and functional pathways that allow us to predict breast cancer behavior in the clinic and provide new targets for breast cancer treatment. This review describes the landscape of different molecular markers with particular spotlight on vitamin D signaling pathway and apoptotic specific protein of p53 (ASPP) family members in breast cancer.