scholarly journals Shared Gene Expression and Immune Pathway Changes Associated with Progression from Nevi to Melanoma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 3
Author(s):  
Elizabeth S. Borden ◽  
Anngela C. Adams ◽  
Kenneth H. Buetow ◽  
Melissa A. Wilson ◽  
Julie E. Bauman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Phase ◽  
Gene Signature ◽  
Linear Change ◽  
Melanoma Progression ◽  
Dysplastic Nevi ◽  
Significant Enrichment ◽  
Bioinformatic Approaches ◽  
Immune Pathway ◽  
Vertical Growth Phase

There is a need to identify molecular biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. Using datasets containing gene expression for dysplastic nevi and melanoma or melanoma arising in a nevus, we performed differential gene expression analysis and regularized regression models to identify genes and pathways that were associated with progression from nevi to melanoma. A small number of genes distinguished nevi from melanoma. Differential expression of seven genes was identified between nevi and melanoma in three independent datasets. C1QB, CXCL9, CXCL10, DFNA5 (GSDME), FCGR1B, and PRAME were increased in melanoma, and SCGB1D2 was decreased in melanoma, compared to dysplastic nevi or nevi that progressed to melanoma. Further supporting an association with melanomagenesis, these genes demonstrated a linear change in expression from benign nevi to dysplastic nevi to radial growth phase melanoma to vertical growth phase melanoma. The genes associated with melanoma progression showed significant enrichment of multiple pathways related to the immune system. This study demonstrates (1) a novel application of bioinformatic approaches to aid clinical trials of melanoma chemoprevention and (2) the feasibility of determining a gene signature biomarker of melanomagenesis.

scholarly journals IL-10 expression by primary tumor cells correlates with melanoma progression from radial to vertical growth phase and development of metastatic competence

2011 ◽  
Vol 24 (6) ◽  
pp. 801-809 ◽  
Author(s):  
Eijun Itakura ◽  
Rong-Rong Huang ◽  
Duan-Ren Wen ◽  
Eberhard Paul ◽  
Peter H Wünsch ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Growth Phase ◽  
Primary Tumor ◽  
Vertical Growth ◽  
Melanoma Progression ◽  
Vertical Growth Phase

scholarly journals Ovarian cycle stage critically affects 21-gene recurrence scores in Mmtv-Pymt mouse mammary tumours

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sarah M. Bernhardt ◽  
Pallave Dasari ◽  
Danielle J. Glynn ◽  
Lucy Woolford ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Menstrual Cycle ◽  
Recurrence Score ◽  
Gene Signature ◽  
Ovarian Cycle ◽  
Oncotype Dx ◽  
Mammary Tumours ◽  
Er Positive ◽  
The Impact

Abstract Background The Oncotype DX 21-gene Recurrence Score is predictive of adjuvant chemotherapy benefit for women with early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. In premenopausal women, fluctuations in estrogen and progesterone during the menstrual cycle impact gene expression in hormone-responsive cancers. However, the extent to which menstrual cycling affects the Oncotype DX 21-gene signature remains unclear. Here, we investigate the impact of ovarian cycle stage on the 21-gene signature using a naturally cycling mouse model of breast cancer. Methods ER-positive mammary tumours were dissected from naturally cycling Mmtv-Pymt mice at either the estrus or diestrus phase of the ovarian cycle. The Oncotype DX 21-gene signature was assessed through quantitative real time-PCR, and a 21-gene experimental recurrence score analogous to the Oncotype DX Recurrence Score was calculated. Results Tumours collected at diestrus exhibited significant differences in expression of 6 Oncotype DX signature genes (Ki67, Ccnb1, Esr1, Erbb2, Grb7, Bag1; p ≤ 0.05) and a significant increase in 21-gene recurrence score (21.8 ± 2.4; mean ± SEM) compared to tumours dissected at estrus (15.5 ± 1.9; p = 0.03). Clustering analysis revealed a subgroup of tumours collected at diestrus characterised by increased expression of proliferation- (p < 0.001) and invasion-group (p = 0.01) genes, and increased 21-gene recurrence score (p = 0.01). No correlation between ER, PR, HER2, and KI67 protein abundance measured by Western blot and abundance of mRNA for the corresponding gene was observed, suggesting that gene expression is more susceptible to hormone-induced fluctuation compared to protein expression. Conclusions Ovarian cycle stage at the time of tissue collection critically affects the 21-gene signature in Mmtv-Pymt murine mammary tumours. Further studies are required to determine whether Oncotype DX Recurrence Scores in women are similarly affected by menstrual cycle stage.

scholarly journals Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 158
Author(s):  
Valentina Condelli ◽  
Giovanni Calice ◽  
Alessandra Cassano ◽  
Michele Basso ◽  
Maria Grazia Rodriquenz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Poor Prognosis ◽  
Cpg Island ◽  
Colon Adenocarcinoma ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cpg Island Methylator Phenotype ◽  
Prognostic Information ◽  
Global Methylation

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.

scholarly journals A novel gene signature based on five immune checkpoint genes predicts the survival of glioma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wei Zhang ◽  
You Zhai ◽  
Guanzhang Li ◽  
Tao Jiang
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Cox Regression ◽  
Gene Signature ◽  
Immune Checkpoints ◽  
The Novel ◽  
The Central Nervous System ◽  
Checkpoint Genes

Abstract Background Glioma is the most common and fatal type of nerve neoplasm in the central nervous system. Several biomarkers have been considered for prognosis prediction, which is not accurate enough. We aimed to carry out a gene signature related to the expression of immune checkpoints which was enough for its performance in prediction. Methods Gene expression of immune checkpoints in TGGA database was filtrated. The 5 selected genes underwent verification by COX and Lasso-COX regression. Next, the selected genes were included to build a novel signature for further analysis. Results Patients were sub-grouped into high and low risk according to the novel signature. Immune response, clinicopathologic characters, and survival showed significant differences between those 2 groups. Terms including “naive,” “effector,” and “IL-4” were screened out by GSEA. The results showed strong relevance between the signature and immune response. Conclusions We constructed a gene signature with 5 immune checkpoints. The signature predicted survival effectively. The novel signature performed more functional than previous biomarkers.

scholarly journals Analysis of blood-based gene expression in idiopathic Parkinson disease

Neurology ◽  
2017 ◽  
Vol 89 (16) ◽  
pp. 1676-1683 ◽  
Author(s):  
Ron Shamir ◽  
Christine Klein ◽  
David Amar ◽  
Eva-Juliane Vollstedt ◽  
Michael Bonin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson Disease ◽  
Gene Networks ◽  
Large Scale ◽  
Expression Profiles ◽  
Area Under The Curve ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Gene Profiles ◽  
Independent Test

Objective:To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples).Methods:Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks.Results:A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E–6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E–4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1, ATP5A1, and VDAC3.Conclusions:We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers.

scholarly journals Contrasting Roles of Ang II and ACEA in the Regulation of IL10 and IL1β Gene Expression in Primary SHR Astroglial Cultures

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3012
Author(s):  
Dhanush Haspula ◽  
Michelle A. Clark
Keyword(s):  
Gene Expression ◽  
Wistar Rats ◽  
Gene Signature ◽  
Brain Regions ◽  
Inhibitory Effect ◽  
Ang Ii ◽  
Cannabinoid Type 1 Receptor ◽  
Il10 Gene ◽  
Cerebellar Astrocytes

Angiotensin (Ang) II is well-known to have potent pro-oxidant and pro-inflammatory effects in the brain. Extensive crosstalk between the primary Ang II receptor, Ang type 1 receptor (AT1R), and the cannabinoid type 1 receptor (CB1R) has been demonstrated by various groups in the last decade. Since activation of glial CB1R has been demonstrated to play a key role in the resolution of inflammatory states, we investigated the role of Ang II (100 nM) and/or ACEA (10 nM), a potent CB1R-specific agonist in the regulation of inflammatory markers in astrocytes from spontaneously hypertensive rats (SHR) and Wistar rats. Astrocytes were cultured from brainstems and cerebellums of SHR and Wistar rats and assayed for IL1β and IL10 gene expression and secreted fraction, in treated and non-treated cells, by employing qPCR and ELISA, respectively. mRNA expression of both IL10 and IL1β were significantly elevated in untreated brainstem and cerebellar astrocytes isolated from SHR when compared to Wistar astrocytes. No changes were observed in the secreted fraction. While ACEA-treatment resulted in a significant increase in IL10 gene expression in Wistar brainstem astrocytes (Log2FC ≥ 1, p < 0.05), its effect in SHR brainstem astrocytes was diminished. Ang II treatment resulted in a strong inhibitory effect on IL10 gene expression in astrocytes from both brain regions of SHR and Wistar rats (Log2FC ≤ −1, p < 0.05), and an increase in IL1β gene expression in brainstem astrocytes from both strains (Log2FC ≥ 1, p < 0.05). Co-treatment of Ang II and ACEA resulted in neutralization of Ang II-mediated effect in Wistar brainstem and cerebellar astrocytes, but not SHR astrocytes. Neither Ang II nor ACEA resulted in any significant changes in IL10 or IL1β secreted proteins. These data suggest that Ang II and ACEA have opposing roles in the regulation of inflammatory gene signature in astrocytes isolated from SHR and Wistar rats. This however does not translate into changes in their secreted fractions.

scholarly journals DNA supercoiling and the anaerobic and growth phase regulation of tonB gene expression.

1988 ◽  
Vol 170 (6) ◽  
pp. 2816-2826 ◽  
Author(s):  
C J Dorman ◽  
G C Barr ◽  
N N Bhriain ◽  
C F Higgins
Keyword(s):  
Gene Expression ◽  
Growth Phase ◽  
Dna Supercoiling ◽  
Phase Regulation

scholarly journals Genetic determinants of growth phase-dependent and adenovirus 5-responsive expression of the Chinese hamster thymidine kinase gene are contained within thymidine kinase mRNA sequences.

1986 ◽  
Vol 6 (6) ◽  
pp. 2262-2266 ◽  
Author(s):  
J A Lewis ◽  
D A Matkovich
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Thymidine Kinase ◽  
Growth Phase ◽  
Chinese Hamster ◽  
Culture Conditions ◽  
Kinase Gene ◽  
Simplex Virus ◽  
Adenovirus 5

We have constructed a chimeric thymidine kinase (TK) minigene, pHe delta 6Ha, which combines the complete coding and 3' noncoding regions of a Chinese hamster TK cDNA with the promoter region and 5' untranslated region of the TK gene of herpes simplex virus type 1. We have transformed rat 4 cells to Tk+ with this gene and analyzed the pattern of TK gene expression in these transformants under various conditions of in vitro cell culture. We find that TK gene expression in these Tk+ transformants is growth phase dependent, responsive to adenovirus 5 infection, and indistinguishable in character under a variety of cell culture conditions from the pattern of TK gene expression in rat 4 cells transformed to Tk+ with the genomic Chinese hamster TK gene clone lambda HaTK.5. We are led to the conclusion that the genetic elements which mediate growth phase-dependent TK gene expression are contained entirely within the sequences of the mature cytoplasmic hamster TK mRNA.

Non-Overlapping and Non–Cell-Type–Specific Gene Expression Signatures Predict Lung Cancer Survival

2008 ◽  
Vol 26 (6) ◽  
pp. 877-883 ◽  
Author(s):  
Zhifu Sun ◽  
Dennis A. Wigle ◽  
Ping Yang
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Signature ◽  
Data Sets ◽  
Cell Type ◽  
Validation Data ◽  
Adjusted Risk ◽  
Gene Expression Signatures

Purpose Gene expression profiling for outcome prediction of non–small-cell lung cancer (NSCLC) remains clouded by heterogeneous and unvalidated results. This study applied multivariate approaches to identify and evaluate value-added gene expression signatures in two types of NSCLC. Materials and Methods Two NSCLC oligonucleotide microarray data sets of adenocarcinoma and squamous cell carcinoma were used as training sets to select prognostic genes independent of conventional predictors. The top 50 genes from each set were used to predict the outcomes of two independent validation data sets of 84 and 91 NSCLC cases. Results Adenocarcinomas with the 50-gene signature from adenocarcinoma in both validation data sets had a 2.4-fold (95% CI, 1.3 to 4.4 and 1.0 to 5.8) increased mortality after adjustment for conventional predictors. Squamous cell carcinoma with this high-risk signature had an adjusted risk of 1.1 (95% CI, 0.4 to 3.2) in one data set and 2.5 (95% CI, 1.1 to 5.8) in another consisting of stage I tumors. Adenocarcinoma with the 50-gene signature from squamous cell carcinoma had an elevated risk of 3.5 (95% CI, 1.4 to 9.0) after adjustment for conventional predictors. Squamous cell carcinoma with this high risk signature had an adjusted risk of 1.8 (95% CI, 0.7 to 4.6). Despite the little overlap in individual genes, the two gene signatures had significant functional connectedness in molecular pathways. Conclusion Two non-overlapping but functionally related gene expression signatures provide consistently improved survival prediction for NSCLC regardless of histologic cell type. Multiple sets of genes may exist for NSCLC with predictive value, but ones with independent predictive value beyond clinical predictors will be required for clinical translation.

scholarly journals Response to FEC Chemotherapy and Oncolytic HSV-1 Is Associated with Macrophage Polarization and Increased Expression of S100A8/A9 in Triple Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5590
Author(s):  
Alyssa Vito ◽  
Nader El-Sayes ◽  
Omar Salem ◽  
Yonghong Wan ◽  
Karen L. Mossman
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Macrophage Polarization ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Differential Gene ◽  
Microarray Analyses ◽  
Tumor Cell Killing

The era of immunotherapy has seen an insurgence of novel therapies driving oncologic research and the clinical management of the disease. We have previously reported that a combination of chemotherapy (FEC) and oncolytic virotherapy (oHSV-1) can be used to sensitize otherwise non-responsive tumors to immune checkpoint blockade and that tumor-infiltrating B cells are required for the efficacy of our therapeutic regimen in a murine model of triple-negative breast cancer. In the studies herein, we have performed gene expression profiling using microarray analyses and have investigated the differential gene expression between tumors treated with FEC + oHSV-1 versus untreated tumors. In this work, we uncovered a therapeutically driven switch of the myeloid phenotype and a gene signature driving increased tumor cell killing.

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