scholarly journals Identification of Biomarkers for Esophageal Squamous Cell Carcinoma Using Feature Selection and Decision Tree Methods

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chun-Wei Tung ◽  
Ming-Tsang Wu ◽  
Yu-Kuei Chen ◽  
Chun-Chieh Wu ◽  
Wei-Chung Chen ◽  
...  
Keyword(s):  
Feature Selection ◽  
Decision Tree ◽  
Squamous Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Design Decision ◽  
Discrimination Ability ◽  
Normal Tissues ◽  
Tree Models

Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.

scholarly journals Transcriptome Analysis in Vulvar Squamous Cell Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6372
Author(s):  
Katharina Prieske ◽  
Malik Alawi ◽  
Anna Jaeger ◽  
Maximilian Christian Wankner ◽  
Kathrin Eylmann ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Rna Expression ◽  
Sequencing Data ◽  
Aberrant Expression ◽  
Distinct Cluster ◽  
Whole Exome Sequencing Data ◽  
Chronic Skin

To date, therapeutic strategies in vulvar squamous cell carcinoma (VSCC) are lacking molecular pathological information and targeted therapy hasn’t been approved in the treatment of VSCC, yet. Two etiological pathways are widely accepted: HPV induced vs. HPV independent, associated with chronic skin disease, often harboring TP53 mutations (mut). The aim of this analysis was to analyze the RNA expression patterns for subtype stratification on VSCC samples that can be integrated into the previously performed whole exome sequencing data for the detection of prognostic markers and potential therapeutic targets. We performed multiplex gene expression analysis (NanoString) with 770 genes in 24 prior next generation sequenced samples. An integrative data analysis was performed. Here, 98 genes were differentially expressed in TP53mut vs. HPV+ VSCC, in the TP53mut cohort, where 56 genes were upregulated and 42 were downregulated in comparison to the HPV+ tumors. Aberrant expression was primarily observed in cell cycle regulation, especially in HPV+ disease. Within the TP53mut group, a distinct cluster was identified that was correlated to a significantly worse overall survival (p = 0.017). The RNA expression profiles showed distinct patterns with regard to the known VSCC subtypes and could potentially enable further subclassification in the TP53mut groups

scholarly journals MicroRNA Expression Profiles in Superficial Esophageal Squamous Cell Carcinoma before Endoscopic Submucosal Dissection: A Pilot Study

2021 ◽  
Vol 22 (9) ◽  
pp. 4789
Author(s):  
Shintaro Fujihara ◽  
Hideki Kobara ◽  
Noriko Nishiyama ◽  
Kayo Hirose ◽  
Hisakazu Iwama ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Endoscopic Submucosal Dissection ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Normal Tissues ◽  
Mirna Expression Profiles

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis when diagnosed at an advanced stage, and early detection and treatment are essential to improve survival. However, intraobserver and interobserver variation make the diagnosis of superficial ESCC difficult, and suitable biomarkers are urgently needed. Here, we compared the microRNA (miRNA) expression profiles of superficial ESCC tissues and adjacent normal tissues obtained immediately before esophageal endoscopic submucosal dissection. We found that ESCC and normal tissues differed in their miRNA expression profiles. In particular, miR-21-5p and miR-146b-5p were significantly upregulated and miR-210-3p was significantly downregulated in tumor tissues compared with normal tissues. We also detected significant associations between miRNA expression and ESCC invasion depth and lymphovascular invasion. The same differential expression of miR-21-5p, miR-146b-5p, and miR-210-3p was detected in ESCC cell lines compared with normal esophageal epithelial cells in vitro. However, transfection of ESCC cells with miR-210-3p and miR-21-5p mimics or inhibitors had partial effects on cell proliferation and invasion in vitro. These results indicate that miRNA expression is significantly deregulated in superficial ESCC, and suggest that the potential contribution of differentially expressed miRNAs to the malignant phenotype should be further investigated.

scholarly journals Novel Dysregulated MicroRNAs in Primary Laryngeal Squamous Cell Cancer

2012 ◽  
Vol 3 (2) ◽  
pp. 76-81 ◽  
Author(s):  
Josena K Stephen ◽  
Kang Mei Chen ◽  
Veena Shah ◽  
Vanessa G Schweitzer ◽  
Glendon Gardner ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Differentially Expressed ◽  
Small Noncoding Rnas ◽  
Real Time Quantitative Pcr ◽  
Normal Tissues ◽  
Human Mirnas ◽  
Human Genes ◽  
Laryngeal Squamous Cell Cancer

ABSTRACT Introduction MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs of 17 to 25 nucleotides that regulate approximately 30% of human genes. They are differentially expressed in various types of cancers compared with noncancerous tissues, suggesting that they may have crucial roles in tumorigenesis. The objective of this study was to identify laryngeal squamous cell cancer (LSCC)-specific miRNAs. Materials and methods A retrospective cohort of 10 LSCC and five normal laryngeal squamous epithelium samples were examined using a global miRNA profiling approach (HTG, Tucson, AZ, USA, 800 human miRNAs plus 10 endogenous control miRNAs). The expression status of selected dysregulated miRNAs that were significantly different from normal were verified by real-time quantitative PCR (qPCR). Results Twenty-three of the 800 human miRNAs had significantly different expression levels (p < 0.05) between LSCC and normal tissues. Fifteen of the 23 have not been previously reported in HNSCC and include: miR-663b, miR-663, miR-193b, miR-1291, miR-720, miR-191, miR-1224-3p, miR-214, miR- 1285, miR-1207-5p, miR-483-5p, miR-1225-3p, miR-1228, miR-1280 and miR-638. Consistently upregulated miR-31 and miR- 193b and differentially expressed miR-663b in LSCC were verified by qPCR. Conclusion The 15 novel miRNAs identified in this exploratory study, pending further confirmation and validation, may have clinical utility as LSCC-specific markers. How to cite this article Chen KM, Stephen JK, Havard S Shah V, Gardner G, Schweitzer VG, Worsham MJ. Novel Dysregulated MicroRNAs in Primary Laryngeal Squamous Cell Cancer. Int J Head Neck Surg 2012;3(2):76-81.

scholarly journals The Effect of NNK, A Tobacco Smoke Carcinogen, on the miRNA and Mismatch DNA Repair Expression Profiles in Lung and Head and Neck Squamous Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1031
Author(s):  
Sotirios G. Doukas ◽  
Dimitra P. Vageli ◽  
George Lazopoulos ◽  
Demetrios A. Spandidos ◽  
Clarence T. Sasaki ◽  
...  
Keyword(s):  
Dna Repair ◽  
Head And Neck ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tobacco Smoking ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Cell Progression ◽  
Squamous Cancer

Tobacco smoking is a common risk factor for lung cancer and head and neck cancer. Molecular changes such as deregulation of miRNA expression have been linked to tobacco smoking in both types of cancer. Dysfunction of the Mismatch DNA repair (MMR) mechanism has also been associated with a poor prognosis of these cancers, while a cross-talk between specific miRNAs and MMR genes has been previously proposed. We hypothesized that exposure of lung and head and neck squamous cancer cells (NCI and FaDu, respectively) to tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is capable of altering the expression of MSH2 and MLH1, key MMR components, by promoting specific miRNA deregulation. We found that either a low (1 μM) or high (2 μM) dose of NNK induced significant upregulation of “oncomirs” miR-21 and miR-155 and downregulation of “tumor suppressor” miR-422a, as well as the reduction of MMR protein and mRNA expression, in NCI and FaDu, compared to controls. Inhibition of miR-21 restored the NNK-induced reduced MSH2 phenotype in both NCI and FaDu, indicating that miR-21 might contribute to MSH2 regulation. Finally, NNK exposure increased NCI and FaDu survival, promoting cancer cell progression. We provide novel findings that deregulated miR-21, miR-155, and miR-422a and MMR gene expression patterns may be valuable biomarkers for lung and head and neck squamous cell cancer progression in smokers.

scholarly journals Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer

2017 ◽  
Author(s):  
Raquel L. Costa ◽  
Mariana Boroni ◽  
Marcelo A. Soares
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Regulatory Elements ◽  
Keratinocyte Differentiation ◽  
External Information ◽  
Hpv Status ◽  
Neck Squamous Cell Cancer

The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). However, a comprehensive understanding of disease progression profiles comparing HPV+ and HPV- HNSCC cases is still lacking. The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV- HNSCC and to provide insights into potential regulatory mechanisms/effects (such as methylation and mutation) within the analyzed networks. For conducting this, we selected 276 samples from The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information (HPV status and tumor staging). We further added external information such as the identification of transcription factors to the networks. Genes were selected as differentially expressed and differentially methylated based on HPV status, of which 12 genes were doubly selected, including SYCP2, GJB6, FLRT3, PITX2 and CCNA1. Weight correlation network analysis was used to identify co-expression modules and a systematic approach was applied to refine them and identify key regulatory elements integrating results from the other omics. Three main modules were associated with distinct co-expression patterns in HPV+ versus HPV- HNSCC. The molecular signatures found were mainly related to cell fate specification, keratinocyte differentiation, focal adhesion and regulation of protein oligomerization. This study provides comprehensive insights into complex genetic and epigenetic particularities in the development and progression of HNSCC in patients according to HPV status, identifying unseen gene interactions, and may contribute to unveiling specific genes/pathways as novel therapeutic targets for HNSCC.

scholarly journals PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung

2021 ◽  
Author(s):  
Torsten Goldmann ◽  
Sebastian Marwitz ◽  
Dörte Nitschkowski ◽  
Rosemarie Krupar ◽  
Max Backman ◽  
...  
Keyword(s):  
Protein Expression ◽  
Squamous Cell ◽  
Immune Cell ◽  
Immune Escape ◽  
Squamous Cell Cancer ◽  
Expression Profiles ◽  
Cell Cancer ◽  
Mutational Status ◽  
Mrna And Protein Expression ◽  
L1 Protein

AbstractGene amplification is considered to be one responsible cause for upregulation of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) and to represent a specific molecular subgroup possibly associated with immunotherapy response. Our aim was to analyze the frequency of PD-L1 amplification, its relation to PD-L1 mRNA and protein expression, and to characterize the immune microenvironment of amplified cases. The study was based on two independent NSCLC cohorts, including 354 and 349 cases, respectively. Tissue microarrays were used to evaluate PD-L1 amplification by FISH and PD-L1 protein by immunohistochemistry. Immune infiltrates were characterized immunohistochemically by a panel of immune markers (CD3, CD4, CD8, PD-1, Foxp3, CD20, CD138, CD168, CD45RO, NKp46). Mutational status was determined by targeted sequencing. RNAseq data was available for 197 patients. PD-L1 amplification was detected in 4.5% of all evaluable cases. PD-L1 amplification correlated only weakly with mRNA and protein expression. About  37% of amplified cases were negative for PD-L1 protein. PD-L1 amplification did not show any association with the mutational status. In squamous cell cancer, PD-L1 amplified cases were enriched among patients with high tumoral immune cell infiltration and showed gene expression profiles related to immune exhaustion. In conclusion, PD-L1 amplification correlates with PD-L1 expression in squamous cell cancer and was associated with an immune cell rich tumor phenotype. The correlative findings help to understand the role of PD-L1 amplification as an important immune escape mechanism in NSCLC and suggest the need to further evaluate PD-L1 amplification as predictive biomarker for checkpoint inhibitor therapy.

scholarly journals RNA sequencing reveals the expression profiles of circRNA and identifies a four-circRNA signature acts as a prognostic marker in esophageal squamous cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weiwei Wang ◽  
Di Zhu ◽  
Zhihua Zhao ◽  
Miaomiao Sun ◽  
Feng Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Rna Sequencing ◽  
Squamous Cell ◽  
Cox Regression ◽  
Expression Profiles ◽  
Characteristic Curve ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background CircRNAs with tissue-specific expression and stable structure may be good tumor prognostic markers. However, the expression of circRNAs in esophageal squamous cell carcinoma (ESCC) remain unknown. We aim to identify prognostic circRNAs and construct a circRNA-related signature in ESCC. Methods RNA sequencing was used to test the circRNA expression profiles of 73 paired ESCC tumor and normal tissues after RNase R enrichment. Bioinformatics methods, such as principal component analysis (PCA), t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm, unsupervised clustering and hierarchical clustering were performed to analyze the circRNA expression characteristics. Univariate cox regression analysis, random survival forests-variable hunting (RSFVH), Kaplan–Meier analysis, multivariable Cox regression and ROC (receiver operating characteristic) curve analysis were used to screen the prognostic circRNA signature. Real-time quantitative PCR (qPCR) and fluorescence in situ hybridization(FISH) in 125 ESCC tissues were performed. Results Compared with normal tissues, there were 11651 differentially expressed circRNAs in cancer tissues. A total of 1202 circRNAs associated with ESCC prognosis (P < 0.05) were identified. Through bioinformatics analysis, we screened a circRNA signature including four circRNAs (hsa_circ_0000005, hsa_circ_0007541, hsa_circ_0008199, hsa_circ_0077536) which can classify the ESCC patients into two groups with significantly different survival (log rank P < 0.001), and found its predictive performance was better than that of the TNM stage(0.84 vs. 0.66; 0.65 vs. 0.62). Through qPCR and FISH experiment, we validated the existence of the screened circRNAs and the predictive power of the circRNA signature. Conclusion The prognostic four-circRNA signature could be a new prognostic biomarker for ESCC, which has high clinical application value.

scholarly journals Integrated transcriptomics explored the cancer-promoting genes CDKN3 in esophageal squamous cell cancer

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wanpeng Wang ◽  
Kai Liao ◽  
Hao Chun Guo ◽  
Suqin Zhou ◽  
Ran Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Kinase Inhibitor ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Expression Level ◽  
Clinical Staging ◽  
Tissue Samples ◽  
Seed Gene ◽  
Significant Difference

Abstract Background and objectives Each individual studies is limited to multi-factors and potentially lead to a significant difference of results among them. The present study aim to explore the critical genes related to the development of Esophageal squamous cell carcinoma (ESCC) by integrated transcriptomics and to investigate the clinical significance by experimental validation. Methods Datasets of protein-coding genes expression which involved in ESCC were downloaded from Gene Expression Omnibus (GEO) database. The “Robustrankaggreg” package in language was used for data integration, and the different expression genes (DEGs) were identified based the cut-off criteria as follows: adjust p-value < 0.05, |fold change (FC)| ≥ 1.5; The protein expression of seed gene in 184 cases of primary ESCC tissues and 50 tumor adjacent normal tissues (at least 5 cm away from the tumor, and defind as the controls) were detected by immunohistochemistry; The relationship between the expression level of seed genes and clinical parameter were analyze. Enumeration data were represented by frequency or percentage (%) and were tested by x2 test. The P value of less than 0.05 was considered statistically significant. Results A total of 244 DEGs were identified by comparing gene expression patterns between ESCC patients and the controls based on integrating dataset of GSE77861, GSE77861, GSE100942, GSE26886, GSE17351, GSE38129, GSE33426, GSE20347 and GSE23400; The Cyclin-dependent kinase inhibitor 3 (CDKN3) were identified the top 1 seed gene of top cluster by use of protein-protein Interaction network and plug-in Molecular Complex Detection; The level of CDKN3 mRNA was significantly increased in ESCC patients compared to controls; The positive expression rate of CDKN3 protein in ESCC tissue samples was 32 and 61.4% in control, respectively. The correlations between the expression level of CDKN3 and lymph node metastasis or clinical staging of ESCC patients are statistically significant. Conclusion Integrated transcriptomics is an efficient approach to system biology. By this procedure, our study improved the understanding of the transcriptome status of ESCC.

scholarly journals Immunohistochemical assays for bladder cancer molecular subtyping: Optimizing parsimony and performance using Lund taxonomy

2021 ◽  
Author(s):  
Céline Hardy ◽  
Hamid Ghaedi ◽  
Ava Slotman ◽  
Gottfrid Sjödahl ◽  
Robert J Gooding ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Decision Tree ◽  
Expression Patterns ◽  
Complex Model ◽  
Proteomic Profiling ◽  
Clinical Implementation ◽  
Antibody Assays ◽  
Tree Models ◽  
And Performance ◽  
Muscle Invasive

Transcriptomic and proteomic profiling reliably classifies bladder cancers into luminal and basal molecular subtypes. Based on their prognostic and predictive associations, these subtypes may improve clinical management of bladder cancers. However, the complexity of published subtyping algorithms has limited their translation into practice. Here we optimize and validate compact subtyping algorithms based on the Lund taxonomy. We reanalyzed immunohistochemistry (IHC) expression data of muscle-invasive bladder cancer samples from Lund 2017 (n=193) and 2012 (n=76) cohorts. We characterized and quantified IHC expression patterns, and determined the simplest, most accurate decision tree models to identify subtypes. We tested the utility of a previously published algorithm using routine antibody assays commonly available in surgical pathology laboratories (GATA3, KRT5 and p16) to identify basal/luminal subtypes and to distinguish between luminal subtypes, Urothelial-Like (Uro) and Genomically Unstable (GU). We determined the dominant decision tree classifiers using four-fold cross-validation with separate uniformly distributed train (75%) and validation (25%) sets. Using the three-antibody algorithm resulted in 86-95% accuracy across training and validation sets for identifying basal/luminal subtypes, and 67-86% accuracy for basal/Uro/GU subtypes. Although antibody assays for KRT14 and RB1 are not routinely used in pathology practice, these features achieved the simplest and most accurate models to identify basal/luminal and Uro/GU/basal subtypes, achieving 93-96% and 85-86% accuracies, respectively. When translated to a more complex model using eight antibody assays, accuracy was comparable to simplified models, with 86% (train) and 82% (validation). We conclude that a simple immunohistochemical classifier can accurately identify luminal (Uro, GU) and basal subtypes and pave the way for clinical implementation.

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