Project description:Analysis of gene expression levels from oral tumor and normal tissue. The purpose of this experiment was to compare profiles of gene expression between tumor and negative margin tissue from matched patient samples.
Project description:Interactions between cancer and immune cells determine the formation and progression of a tumor. Variability of immune contextures in tumor and margins among patients with oral squamous cell carcinoma of the gingivobuccal region (OSCC-GB) – the most prevalent subtype of oral cancer in India and southeast Asia – and the relationship of these contextures with prognosis are largely unknown. Treatment naïve, HPV negative, OSCC-GB patients (n=46) were recruited, treated, followed-up for two years and recurrence/death noted. Immune contextures of tumor and negative margins were studied using RNA-sequencing and immunohistochemistry (n=43; margin tissues were unavailable from three patients). Expressions of 544 immune related genes (IRGs) revealed a subgroup of patients (28%) with poor prognosis (high recurrence and death). The compositions of immune cell-types of normal and negative margin tissues were similar among patients irrespective of prognoses; differences were observed only in tumor.
Project description:The 5-year survival rate for patients with oral squamous cell carcinomas (SCC), including tongue SCC, has not significantly improved over the last several decades. Oral potentially malignant disorders (OPMD), including oral dysplasias, are oral epithelial disorders that can develop into oral SCCs. To identify molecular characteristics that might predict conversion of OPMDs to SCCs and guide treatment plans, we performed global transcriptomic analysis of human tongue OPMD (n=9) and tongue SCC (n=11) samples with paired normal margin tissue from patients treated at Weill Cornell Medicine. Compared to margin tissue, SCCs showed more transcript changes than OPMDs. OPMDs and SCCs shared some altered transcripts, but these changes were generally greater in SCCs than OPMDs. Both OPMDs and SCCs showed altered signaling pathways related to cell migration, basement membrane disruption, and metastasis. We suggest that OPMDs were on the path towards malignant transformation. Based in patterns of gene expression, both OPMD samples and SCC samples can be categorized into subclasses (mesenchymal, classical, basal, and atypical) similar to those seen in human head and neck SCC (HNSCC). These subclasses of OPMDs the potential to be used to stratify patient prognosis and therapeutic options for tongue OPMDs. Lastly, we developed Firth logistic regression models to classify OPMDs and SCCs using a signature gene set ELF5, RPTN, IGSF10, HTR3A, and CRMP1, and this predictive model is amenable to testing as data sets become available. We suggest that changes in these five transcripts relative to paired normal tissue could be used to predict of the likelihood of an OPMD developing into a SCC.
Project description:Oral squamous cell carcinoma (OSCC) is highly heterogeneous and metastatic, and the mechanisms driving OSCC development, progression, and metastasis are poorly understood. We performed multiregional single-cell RNA sequencing on 268,131 cells obtained from tumor core, tumor periphery, adjacent non-tumor tissue, and metastatic lymph node samples from 10 patients with human papillomavirus (HPV)–negative metastatic OSCC.
Project description:Lung cancer is responsible for the most cancer-related mortality worldwide and the mechanism of its development is poorly understood. Proteomics has become a powerful tool offering vital knowledge related to cancer development. Using a two-dimensional difference gel electrophoresis (2D-DIGE) approach, we sought to compare tissue samples from non-small-cell lung cancer (NSCLC) patients, exactly adenocarcinoma (ADC), taken from the tumor center and tumor margin and control (adjacent non-tumor) tissues . We found 22 differentially abundant spots representing 17 proteins differentiating center and margin. Sixty eight proteins; represented by 79 spots :40, 20, and 19 spots differed between the control and center and margin, control and center, and control and margin, respectively. Twenty six significant canonical pathways were identified, including Rho signaling pathways, a semaphorin neuronal repulsive signaling pathway, and epithelial adherens junction signaling. Proteins differentiating the tumor center and tumor margin were linked to cancer invasion and progression, including cell migration, adhesion and invasion, cytoskeletal structure, protein folding, anaerobic metabolism, tumor angiogenesis, EMC transition, epithelial adherens junctions, and inflammatory responses.
Project description:Basic analysis of 5 pairs of tumor margin and invasive OSCC tumor tissue using basic nsolver analysis showed, PD-L1 and IFN-γ 6 gene signature to be higher in morphologically normal epithelial tumor margin than in dysplastic tumor margin, yet the invasive OSCC area was the highest in PD-L1 and IFN-γ 6 gene signature. It also demosntrates 38 significant Immuno oncologic gene signature for maligant transformation relative to tumor margins.
Project description:Lung cancer is responsible for the most cancer-related mortality worldwide and the mechanism of its development is poorly understood. Proteomics has become a powerful tool offering vital knowledge related to cancer development. Using a two-dimensional difference gel electrophoresis (2D-DIGE) approach, we sought to compare tissue samples from non-small-cell lung cancer (NSCLC) patients, exactly squamous cell carcinoma (SCC), taken from the tumor center and tumor margin and control (adjacent non-tumor) tissues. We found and 21 spots representing 20 proteins differentiating center and margin. We found 111 differentially expressed protein spots representing 95 proteins; 84, 7, and 20 spots differed between the control and center and margin, control and center, and control and margin, respectively. Nine significant canonical pathways were identified, including hypoxia-inducible factor-1α signaling, thyroid hormone biosynthesis, and phagosome maturation. Several pathways related to disease and function were identified as related to cell death and survival, and several related to cancer, organismal injury, and abnormalities. Proteins differentiating the tumor center and tumor margin were linked to cancer invasion and progression, including cell migration, adhesion and invasion, cytoskeletal structure, protein folding, anaerobic metabolism, tumor angiogenesis, epithelialmesenchymal transition, epithelial adherens junctions, and inflammatory responses.
Project description:RNA-Seq was applied to oral squamous cell carcinomas and matched normal oral tissue to measure gene expression patterns and identify examples of allelic imbalance. Oral squamous cell carcinomas (OSCC) and matched normal tissue from 3 patients.
Project description:Background: The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. Methods: The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). The 20 patients were then grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients by quantitative real-time RT-PCR. Results: Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3, HSAL2 and PACE4, respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.0467). In survival studies, only GLUT3 showed a prognostic value with disease-specific (P=0.049), relapse-free (P-0.0042) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. Conclusions: The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma. Keywords: gene expression profiling The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). The 20 patients were then grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3, HSAL2, and PACE4, were selected for their potential biological significance in a larger cohort of 49 patients by quantitative real-time RT-PCR