Disruption of the Non-Canonical WNT Pathway in Lung Squamous Cell Carcinoma

2008 ◽  
Vol 2 ◽  
pp. CMO.S612 ◽  
Author(s):  
Eric H.L. Lee ◽  
Raj Chari ◽  
Andy Lam ◽  
Raymond T. Ng ◽  
John Yee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Wnt Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Beta Catenin ◽  
Related Protein ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

Disruptions of beta-catenin and the canonical Wnt pathway are well documented in cancer. However, little is known of the non-canonical branch of the Wnt pathway. In this study, we investigate the transcript level patterns of genes in the Wnt pathway in squamous cell lung cancer using reverse-transcriptase (RT)-PCR. It was found that over half of the samples examined exhibited dysregulated gene expression of multiple components of the non-canonical branch of the WNT pathway. In the cases where beta catenin ( CTNNB1) was not over-expressed, we identified strong relationships of expression between wingless-type MMTV integration site family member 5A ( WNT5A)/ frizzled homolog 2 ( FZD2), frizzled homolog 3 ( FZD3)/ dishevelled 2 ( DVL2), and low density lipoprotein receptor-related protein 5 ( LRP5)/ secreted frizzled-related protein 4 ( SFRP4). This is one of the first studies to demonstrate expression of genes in the non-canonical pathway in normal lung tissue and its disruption in lung squamous cell carcinoma. These findings suggest that the non-canonical pathway may have a more prominent role in lung cancer than previously reported.

EXPRESSION ANALYSIS OF CANONICAL WNT PATHWAY GENES IN ORAL SQUAMOUS CELL CARCINOMA AND THEIR POSSIBLE ROLE AS BIOMARKERS

2017 ◽  
Vol 124 (3) ◽  
pp. e197
Author(s):  
MADHULAXMI MARIMUTHU ◽  
P.U. ABDUL WAHAB ◽  
ANANDAN BALAKRISHNAN ◽  
SAMBANDHAM SHANMUGAM ◽  
VINOD NARAYANAN ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Expression Analysis ◽  
Squamous Cell ◽  
Wnt Pathway ◽  
Canonical Wnt Pathway ◽  
Canonical Wnt

scholarly journals Canonical Wnt pathway gene expression and their clinical correlation in oral squamous cell carcinoma

2018 ◽  
Vol 29 (3) ◽  
pp. 291 ◽  
Author(s):  
Madhulaxmi Marimuthu ◽  
Manoharan Andiappan ◽  
Abdul Wahab ◽  
MR Muthusekhar ◽  
Anandan Balakrishnan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Wnt Pathway ◽  
Clinical Correlation ◽  
Canonical Wnt Pathway ◽  
Pathway Gene ◽  
Canonical Wnt

scholarly journals UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Rna Expression

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.

scholarly journals Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2071 ◽  
Author(s):  
Patricia P. Reis ◽  
Sandra A. Drigo ◽  
Robson F. Carvalho ◽  
Rainer Marco Lopez Lapa ◽  
Tainara F. Felix ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Genes ◽  
Lung Squamous Cell Carcinoma ◽  
High Specificity ◽  
Mirna Signature ◽  
Lung Tumorigenesis ◽  
Lung Cancer Patients

Background: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate lung oncogenesis pathways. Methods: RNA isolated from 139 plasma samples (40 LUAD, 38 LUSC; 61 healthy/non-diseased individuals) were divided into discovery (38 patients; 21 controls for expression quantification using an 800-miRNA panel; Nanostring nCounter®) and validation (40 patients; 40 controls; TaqMan® RT-qPCR) cohorts. Elastic net, Maximizing-R-Square Analysis (MARSA), and C-Statistics were applied for miRNA signature identification. Results: When compared to healthy individuals, 580 of 606 deregulated miRNAs in LUAD and 221 of 226 deregulated miRNAs in LUSC had significantly increased levels. Among the 10 most significantly overexpressed miRNAs, 6 were common to patients with LUAD and LUSC. Further analysis identified three signatures composed of 12 miRNAs. Signatures included miRNAs commonly overexpressed in patient plasma. Enriched pathways included target genes modulated by three miRNAs in the C-Statistics signature: miR-16-5p, miR-92a-3p, and miR-451a. Conclusions: The 3-miRNA signature (miR-16-5p, miR-92a-3p, miR-451a) had high specificity (100%) and sensitivity (84%) to predict cancer (LUAD and LUSC). These miRNAs are predicted to modulate genes and pathways with known roles in lung tumorigenesis, including EGFR, K-RAS, and PI3K/AKT signaling, suggesting that the 3-miRNA signature is biologically relevant in adenocarcinoma and squamous cell carcinoma of the lung.

scholarly journals Exosomal miRNAs as Novel Pharmacodynamic Biomarkers for Cancer Chemopreventive Agent Early Stage Treatments in Chemically Induced Mouse Model of Lung Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 477 ◽  
Author(s):  
Yu Zhou ◽  
Qi Zhang ◽  
Meijun Du ◽  
Donghai Xiong ◽  
Yian Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Lung Squamous Cell Carcinoma ◽  
P Values ◽  
Chemopreventive Agent ◽  
Exosomal Mirnas ◽  
Pharmacodynamic Biomarkers

Background: Chemopreventive agent (CPA) treatment is one of the main preventive options for lung cancer. However, few studies have been done on pharmacodynamic biomarkers of known CPAs for lung cancer. Materials and methods: In this study, we treated mouse models of lung squamous cell carcinoma with three different CPAs (MEK inhibitor: AZD6244, PI-3K inhibitor: XL-147 and glucocorticoid: Budesonide) and examined circulating exosomal miRNAs in the plasma of each mouse before and after treatment. Results: Compared to baselines, we found differentially expressed exosomal miRNAs after AZD6244 treatment (n = 8, FDR < 0.05; n = 55, raw p-values < 0.05), after XL-147 treatment (n = 4, FDR < 0.05; n = 26, raw p-values < 0.05) and after Budesonide treatment (n = 1, FDR < 0.05; n = 36, raw p-values < 0.05). In co-expression analysis, we found that modules of exosomal miRNAs reacted to CPA treatments differently. By variable selection, we identified 11, 9 and nine exosomal miRNAs as predictors for AZD6244, XL-147 and Budesonide treatment, respectively. Integrating all the results, we highlighted 4 miRNAs (mmu-miR-215-5p, mmu-miR-204-5p, mmu-miR-708-3p and mmu-miR-1298-5p) as the key for AZD6244 treatment, mmu-miR-23a-3p as key for XL-147 treatment, and mmu-miR-125a-5p and mmu-miR-16-5p as key for Budesonide treatment. Conclusions: This is the first study to use circulating exosomal miRNAs as pharmacodynamic biomarkers for CPA treatment in lung cancer.

scholarly journals Pathological and Prognostic Indications of the mdig Gene in Human Lung Cancer

2021 ◽  
Vol 55 (S2) ◽  
pp. 13-28
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Human Lung Cancer ◽  
Clinical Samples ◽  
Lung Carcinogenesis ◽  
Expression Status

Background/Aims: The mineral-dust-induced gene mdig is a lung-cancer-associated oncogene. The focus of this study is to evaluate the expression status of mdig in lung cancer and to assess its influence in predicting the patient’s overall survival. Methods: Using high-density tissue microarrays and clinical samples of synchronous multiple primary lung cancer (SMPLC), we investigated the expression of mdig through immunohistochemistry and utilized the open-access lung cancer patient databases containing genomic and transcriptomic data from the UCSC Xena and TCGA web platforms to determine the prognostic values of mdig expression status among different subtypes of lung cancer. Results: mdig is upregulated in smokers and in lung squamous cell carcinoma. High mdig expression predicted poor overall survival in lung squamous cell carcinoma and female smokers. Among tumor tissues from SMPLC patients, we not only unraveled the highest positive rate of mdig expression, but also revealed a unique cytoplasmic, rather than nuclear localization of mdig protein. Furthermore, by inspecting some pathological but not cancerous lung tissues, we believe that mdig is required for the transformation of non-cancerous lung cells to the fully-fledged cancer cells. Conclusion: These data suggested that mdig is involved in various stages of lung carcinogenesis, possibly through the epigenetic regulation on some critical cancer-associated genes, and increased mdig expression is an important prognostic factor for some types of lung cancer.

scholarly journals The Regulators Associated With N6-Methyladenosine in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Reveal New Clinical and Prognostic Markers

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuzhen Tan ◽  
Zesong Li ◽  
Kai Li ◽  
Yingqi Li ◽  
Guosheng Liang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Markers ◽  
Cox Regression ◽  
Lung Squamous Cell Carcinoma ◽  
Lung Cancers ◽  
Pathological Characteristics

N6-methyladenosine (m6A) methylation is of significant importance in the initiation and progression of tumors, but how specific genes take effect in different lung cancers still needs to be explored. The aim of this study is to analyze the correlation between the m6A RNA methylation regulators and the occurrence and development of lung cancer. The data of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) were obtained through the TCGA database. We systematically analyzed the related pathological characteristics and prognostic factors by applying univariate and multivariate Cox regression, as well as LASSO Cox regression. Some of 23 m6A regulators are identified as having high expression in lung cancer. In addition, risk score has been shown to be an independent prognostic factor in lung cancer. Our research not only fully reveals that m6A regulators and clinical pathological characteristics are potentially useful with respect to survival and prognosis in different lung tumors but also can lay a theoretical root for the treatment for lung cancer—notably, to point out a new direction for the development of treatment.

scholarly journals CENPF driven lung adenocarcinoma and lung squamous cell carcinoma with immune infiltrates

2020 ◽  
Author(s):  
Lei Li ◽  
Pengchao Zheng
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cd8 T Cells ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Marker

Abstract Background: CENPF (centromere protein F) is a critical gene that associates with the centromere-kinetochore complex and plays an important role in the tumor development. However, the associations of CENPF expression and tumor infiltrating lymphocytes in lung cancer remain unknown. Methods : CENPF expression and prognostic factor was analyzed via the Gene Expression Profiling Interactive Analysis (GEPIA) site. The correlation between CENPF and cancer immune infiltrates was investigated via and Tumor Immune Estimation Resource (TIMER) site. Further, correlations between CENPF expression and gene marker sets of immune infiltrates were analyzed by TIMER. Results: The TCGA database of Lung adenocarcinoma(LUAD) and Lung squamous cell carcinoma(LUSC) patients showed that high CENPF expression was associated with poorer overall survival (OS HR=1.5,P=0.01) and disease-free survival (DFS HR=1.4,P=0.027) in LUAD. Specifically, high CENPF expression have no correlated with worse OS(OS HR=0.78,P=0.071) and DFS(DFS HR=1,P=0.87) in LUSC. CENPF expression was positively correlated with infiltrating levels of B cells, macrophage in LUAD, B cells, and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in LUSC. CENPF expression showed strong correlations with diverse immune marker sets in LUAD, and LUSC. After down-regulating the expression of CENPF, the proliferative capacity of Lung adenocarcinoma and Lung squamous cell carcinoma cells was inhibited. Conclusions: This report suggest that CENPF is high expression, correlated with poor prognosis and immune infiltrating levels of, including those of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in in LUAD and LUSC. In addition, CENPF expression is potentially closely related to the proliferation and metastasis of lung cancer cells. These studies suggest that CENPF can be used as a new prognostic target for determining prognosis and immune infiltration in Lung adenocarcinoma and Lung squamous cell carcinoma.

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