scholarly journals Gene Expression Profiling Reveals Reproducible Human Lung Adenocarcinoma Subtypes in Multiple Independent Patient Cohorts

2006 ◽  
Vol 24 (31) ◽  
pp. 5079-5090 ◽  
Author(s):  
D. Neil Hayes ◽  
Stefano Monti ◽  
Giovanni Parmigiani ◽  
C. Blake Gilks ◽  
Katsuhiko Naoki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Carcinoma ◽  
Dna Microarray ◽  
Early Stage ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Early Stage Disease ◽  
Tumor Subtypes ◽  
Difference Statistic ◽  
Lung Adenocarcinomas

Purpose Published reports suggest that DNA microarrays identify clinically meaningful subtypes of lung adenocarcinomas not recognizable by other routine tests. This report is an investigation of the reproducibility of the reported tumor subtypes. Methods Three independent cohorts of patients with lung cancer were evaluated using a variety of DNA microarray assays. Using the integrative correlations method, a subset of genes was selected, the reliability of which was acceptable across the different DNA microarray platforms. Tumor subtypes were selected using consensus clustering and genes distinguishing subtypes were identified using the weighted difference statistic. Gene lists were compared across cohorts using centroids and gene set enrichment analysis. Results Cohorts of 31, 72, and 128 adenocarcinomas were generated for a total of 231 microarrays, each with 2,553 reliable genes. Three adenocarcinoma subtypes were identified in each cohort. These were named bronchioid, squamoid, and magnoid according to their respective correlations with gene expression patterns from histologically defined bronchioalveolar carcinoma, squamous cell carcinoma, and large-cell carcinoma. Tumor subtypes were distinguishable by many hundreds of genes, and lists generated in one cohort were predictive of tumor subtypes in the two other cohorts. Tumor subtypes correlated with clinically relevant covariates, including stage-specific survival and metastatic pattern. Most notably, bronchioid tumors were correlated with improved survival in early-stage disease, whereas squamoid tumors were associated with better survival in advanced disease. Conclusion DNA microarray analysis of lung adenocarcinomas identified reproducible tumor subtypes which differ significantly in clinically important behaviors such as stage-specific survival.

scholarly journals Microarray Analysis of Serum mRNA in Patients with Head and Neck Squamous Cell Carcinoma at Whole-Genome Scale

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Markéta Čapková ◽  
Jana Šáchová ◽  
Hynek Strnad ◽  
Michal Kolář ◽  
Miluše Hroudová ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Microarray Analysis ◽  
Squamous Cell ◽  
Early Stage ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Neck Squamous Cell Carcinoma

With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey’sPvalue<0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.

scholarly journals Gene Expression Patterns in Renal Cell Carcinoma Assessed by Complementary DNA Microarray

2003 ◽  
Vol 162 (3) ◽  
pp. 925-932 ◽  
Author(s):  
John P.T. Higgins ◽  
Rajesh Shinghal ◽  
Harcharan Gill ◽  
Jeffrey H. Reese ◽  
Martha Terris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Dna Microarray ◽  
Renal Cell ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Complementary Dna

scholarly journals Signet-Ring Cell Carcinoma of the Colon: A Case Report and Review of the Literature

2015 ◽  
Vol 8 (3) ◽  
pp. 466-471 ◽  
Author(s):  
Peter Y. Park ◽  
Teresa Goldin ◽  
John Chang ◽  
Maurie Markman ◽  
Madappa N. Kundranda
Keyword(s):  
Cell Carcinoma ◽  
Early Stage ◽  
Single Agent ◽  
The United States ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Early Stage Disease ◽  
Lower Quadrant ◽  
Signet Ring ◽  
Ring Cell

Background: Colorectal adenocarcinoma (CRC) is the third leading cause of death in the United States. One of the histologic subtypes of CRC is signet-ring cell carcinoma (SRCC), which has a distinct molecular and tumor biology from that of adenocarcinoma. Primary SRCC diagnosed at an early stage is very rare as most cases are detected at an advanced stage. Therefore, overall prognosis of SRCC is poor. Case Presentation: A 36-year-old female presented to her primary care physician with new-onset progressive right lower quadrant pain without any significant past medical or family history. Computed tomography scan of the abdomen and pelvis with contrast showed a 4.9 × 3.5 × 3.1 cm, lobulated, septated cystic mass arising from the cecum. The mass demonstrated wall enhancement and contained focal areas of coarse calcification. There was nodal involvement either locally or distally. The patient underwent right hemicolectomy, and pathology revealed a high-grade mucinous carcinoma with signet-ring cell variant invading through the muscularis propria and into the subserosal adipose tissue. The margins were negative for tumor, and no lymphovascular or perineural invasion was noted. None of the 14 resected pericolonic lymph nodes was positive for malignancy. Hence, she was staged as pT3, pN0, pMx-stage IIA. The appendix was not involved. Microsatellite instability testing showed the preservation of MLH1, PMS2, MSH2 and MSH6 proteins by IHC and PCR. Carcinoembryonic antigen level was within normal limits. Due to the patient's young age, aggressive histology and microsatellite-stable status, adjuvant fluropyrimidine (5-FU)-based therapy with the single agent capecitabine was initiated. The patient completed 6 months of adjuvant therapy and has been disease free for approximately 18 months. Conclusion: Primary SRCC of the cecum is a rare disease. Given the poor prognosis of these patients, early-stage disease with microsatellite-stable patients should be considered for adjuvant 5-FU-based therapy in an attempt to prevent recurrence.

scholarly journals The Functionalities and Clinical Significance of Tumor-Infiltrating Immune Cells in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jishuai Zhang ◽  
Haifeng Wang ◽  
Haitao Wu ◽  
Guangliang Qiang
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Natural Killer ◽  
Clinical Significance ◽  
Squamous Cell ◽  
Immune Cells ◽  
Gene Set Enrichment Analysis

Tumor-infiltrating immune cells have been implicated in the tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC). However, the functionalities and clinical significance of immune cells remain largely unveiled. In this study, the gene expression data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were extracted. The relative infiltrating levels were estimated by single-sample gene set enrichment analysis. Some cytotoxic immune cells were attenuated, and resting cytotoxic immune cells were accumulated in ESCC. Remarkably, we also observed that infiltrating levels of macrophage M2 and resting natural killer (NK) cells were increased in nonresponders of CRT, and T cells that had anticancer activities such as activated memory CD4 and T helper 2 (Th2) cells were significantly reduced in ESCC tissues of the nonresponders. Moreover, the high infiltrations of the resting natural killer (NK) and dendritic cell (DC) were observed to result in a shorter overall survival in ESCC. Consistently, high expression of immune checkpoint genes, CTLA4 and HAVCR2, was associated with poor prognosis. Furthermore, STAT5B, a key transcription factor, as well as its target genes, involved in the regulation of T cells, was significantly downregulated in ESCC, especially subgroup I, indicating that downregulation of STAT5B might be associated with reduced T cell-mediated anticancer activity. In conclusion, the present study significantly improved our understanding of the regulatory roles of immune cells in ESCC.

scholarly journals Fetal Membrane Epigenetics

2020 ◽  
Vol 11 ◽  
Author(s):  
Tamas Zakar ◽  
Jonathan W. Paul
Keyword(s):  
Gene Expression ◽  
Early Stage ◽  
Expression Patterns ◽  
Normal Pregnancy ◽  
Clinical Samples ◽  
Fetal Membrane ◽  
Stage Of Development ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
Adverse Pregnancy

The characteristics of fetal membrane cells and their phenotypic adaptations to support pregnancy or promote parturition are defined by global patterns of gene expression controlled by chromatin structure. Heritable epigenetic chromatin modifications that include DNA methylation and covalent histone modifications establish chromatin regions permissive or exclusive of regulatory interactions defining the cell-specific scope and potential of gene activity. Non-coding RNAs acting at the transcriptional and post-transcriptional levels complement the system by robustly stabilizing gene expression patterns and contributing to ordered phenotype transitions. Here we review currently available information about epigenetic gene regulation in the amnion and the chorion laeve. In addition, we provide an overview of epigenetic phenomena in the decidua, which is the maternal tissue fused to the chorion membrane forming the anatomical and functional unit called choriodecidua. The relationship of gene expression with DNA (CpG) methylation, histone acetylation and methylation, micro RNAs, long non-coding RNAs and chromatin accessibility is discussed in the context of normal pregnancy, parturition and pregnancy complications. Data generated using clinical samples and cell culture models strongly suggests that epigenetic events are associated with the phenotypic transitions of fetal membrane cells during the establishment, maintenance and termination of pregnancy potentially driving and consolidating the changes as pregnancy progresses. Disease conditions and environmental factors may produce epigenetic footprints that indicate exposures and mediate adverse pregnancy outcomes. Although knowledge is expanding rapidly, fetal membrane epigenetics is still in an early stage of development necessitating further research to realize its remarkable basic and translational potential.

Enchanced Expression of Gene Data

2011 ◽  
Vol 403-408 ◽  
pp. 780-786
Author(s):  
Rashmi G. Dukhi
Keyword(s):  
Gene Expression ◽  
Dna Microarray ◽  
Expression Patterns ◽  
Divide And Conquer ◽  
Genome Wide Data ◽  
Data Objects ◽  
Gene Expression Data Clustering ◽  
Related Proteins ◽  
Gene Data ◽  
Or Genes

DNA microarray analysis has become the most widely used functional genomics approach in the bioinformatics field. Biologists are vastly plagued by the enormous amount of unprecedented qualities of genome-wide data produced by the DNA Microarray experiment.Clustering is the process of grouping data objects into set of disjoint classes called clusters so that objects within a class are highly similar with one another and dissimilar with the objects in other classes. It is presently the far most used method for gene expression analysis which provides a divide-and–conquer strategy to extract meaningful information from expression profile.In transcriptomics,clustering is used to build groups of genes with related expression patterns (also known as coexpressed genes). Often such groups contain functionally related proteins, such as enzymes for a specific pathway, or genes that are co-regulated. This paper presents a review on the recently development of microarray clustering techniques followed by the different categories of gene expression data clustering.

scholarly journals The Expression of Human Placental Genes Related to Carotenoid/retinoid Metabolism and Pathways (P02-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xiaoming Gong ◽  
Lewis Rubin
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Fetal Development ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Retinoid Metabolism ◽  
Expression Of Genes ◽  
Β Carotene

Abstract Objectives Carotenoid/retinoids status and metabolism are essential for normal placental and fetal development. Both deficiencies and excess of retinoids and some carotenoids are associated with adverse pregnancy outcomes, such as preeclampsia and preterm birth. A group of important genes involved in regulating carotenoid/retinoid metabolism and maternal to fetal transfer in human placenta. The objective of this study is to analyze (a) the expression of genes critical for regulating carotenoid/retinoid metabolism and maternal-fetal transport in human trophoblasts and (b) placental transcriptional profiles of these pathways in response to carotenoid exposure. Methods Human cytotrophoblasts (CTBs) were isolated from term placentas. CTB RNA was used to analyze the expression of genes involved in carotenoid/retinoid metabolism and pathways by qRT-PCT. First trimester-like trophoblasts (HTR-8/SVneo) were treated with either β-carotene or lycopene. RNAs were isolated and gene expression were analyzed by DNA microarrays. Results Human CTBs express retinoid metabolism and pathways-related genes, including Stra6, Lrat, Rdh5, Rdh10, Aldh1a1, Aldh1a2, Aldh1a3, Aldh8a1, Cyp26a1, and Cyp26b1, but not carotenoid metabolism genes, BCO1 and BCO2. Microarray analysis of placental gene expression profile revealed a total of 872 and 756 differentially expressed genes, respectively, compared to the control. Gene set enrichment analysis and functional annotation clustering was performed to characterize the genes differentially expressed in either β-carotene or lycopene-treated HTR-8/SVneo cells. Many known retinoid metabolism related genes and genes involved in regulation of retinoid signaling were found, and the expression profiles of these genes were markedly different in response to β-carotene treatments. Finally, the qRT-PCR and microarray analysis results showed similar gene expression patterns of carotenoid/retinoid metabolism and pathways. Conclusions These findings suggest that placental expression of genes involved in retinoid metabolism and transport in trophoblasts is critical for regulating retinoid homeostasis during placental and fetal development. Carotenoid exposure in early placental development, significantly modify the placenta gene expression related to retinoid pathways and maternal to fetal transfer. Funding Sources NIH HD421174.

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