E2F1 overexpression associated with TS and survivin gene expressions in non-small cell lung cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7669-7669 ◽  
Author(s):  
C. Huang ◽  
D. Liu ◽  
J. Nakano ◽  
S. Ishikawa ◽  
H. Yokomise ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Survivin Expression ◽  
Apoptotic Index ◽  
Proliferation Index ◽  
Small Cell Lung ◽  
Gene Expressions ◽  
Ki 67 ◽  
Survivin Gene ◽  
Nsclc Patients

7669 Background: The thymidylate synthase (TS) expression is related to 5-FU sensitivity. The survivin expression is associated with tumor apoptosis, an indicator to predict the efficacy of chemotherapy. Recently, TS and Survivin have been reported to be E2F1 target genes. We investigate the clinical significance of the E2F1 gene expression in relation to gene expressions of TS and Survivin among non-small cell lung cancer (NSCLC). Methods: One hundred and twenty-seven NSCLC patients were investigated. Quantitative RT-PCR was performed to evaluate gene expressions of E2F1, TS, and survivin. The Ki-67 proliferation index and the apoptotic index using TUNEL method were also evaluated. Results: The E2F1 gene expression was significantly higher in stage II to III tumors than in stage I tumors (p=0.006). The E2F1 gene expression significantly correlated with the Ki-67 proliferation index (p<0.001), while no correlation was observed between the E2F1 gene expression and the apoptotic index. Regarding E2F1-target genes, the E2F1 gene expression significantly correlated with the TS gene expression (p<0.001). The E2F1 gene expression also significantly correlated with the survivin gene expression (p<0.001). The TS expression and the survivin expression significantly correlated with the Ki-67 proliferation index (p<0.001 and p<0.001, respectively). There was a significant inverse relationship between the survivin expression and the apoptotic index (p<0.001). The overall survival was significantly lower in patients with high-E2F1 tumors than in those with low-E2F1 tumors (p=0.002), especially among patients with stage II to III NSCLCs (p=0.018). The Cox regression analysis demonstrated that the E2F1 status was a significant prognostic factor for NSCLC patients (p=0.026). Conclusions: The present study revealed the E2F1 gene expression to correlate with TS and survivin gene expressions, and tumor proliferation. E2F1 overexpression could occur to produce more aggressive tumors with high proliferation rate and chemo-resistance during progression of NSCLCs. The suppression of E2F1 by RNA interference would be a useful strategy for cancer gene therapy. No significant financial relationships to disclose.

Wnt5a Expression Is Associated With the Tumor Proliferation and the Stromal Vascular Endothelial Growth Factor—An Expression in Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (34) ◽  
pp. 8765-8773 ◽  
Author(s):  
Cheng-long Huang ◽  
Dage Liu ◽  
Jun Nakano ◽  
Shinya Ishikawa ◽  
Keiichi Kontani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Proliferation Index ◽  
Beta Catenin ◽  
Vascular Endothelial ◽  
Small Cell Lung ◽  
Ki 67 ◽  
Wnt5a Expression ◽  
Endothelial Growth Factor

Purpose The Wnt gene family encodes the multifunctional signaling glycoproteins. We performed the present study to investigate the clinical significance of Wnt5a expression in non–small-cell lung cancer (NSCLC). Patients and Methods One hundred twenty-three patients with NSCLC who had undergone resection were investigated. Real-time quantitative reverse transcriptase polymerase chain reaction was performed to evaluate the Wnt5a gene expression. Immunohistochemistry was performed to investigate the Wnt5a protein expression, the Ki-67 proliferation index, tumor angiogenesis, and the expression of beta-catenin and vascular endothelial growth factor-A (VEGF-A). Results Wnt5a gene expression in squamous cell carcinoma was significantly higher than that in adenocarcinoma (P < .0001). There was a significant correlation between the normalized Wnt5a gene expression ratio and the intratumoral Wnt5a protein expression (r = 0.729; P < .0001). The intratumoral Wnt5a expression was significantly correlated with the Ki-67 proliferation index (r = 0.708; P < .0001). In contrast, no correlation was observed between the intratumoral Wnt5a expression and tumor angiogenesis. Furthermore, the intratumoral Wnt5a expression was significantly correlated with the stromal expression of beta-catenin (r = 0.729; P < .0001) and VEGF-A (r = 0.661; P < .0001). In addition, the stromal VEGF-A expression was also correlated with Ki-67 proliferation (r = 0.627; P < .0001). Cox regression analyses demonstrated Wnt5a status to be a significant prognostic factor for NSCLC patients (P = .0193), especially for patients with squamous cell carcinomas (P = .0491). Conclusion The present study revealed that an overexpression of Wnt5a could produce more aggressive NSCLC, especially in squamous cell carcinomas, during tumor progression.

Low Expression of SCN4B Correlated with DNA Hypermethylation and Poor Prognosis in Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Meixiang Yu ◽  
Zi Wang ◽  
Qianzhou Lv ◽  
Wanhua Yang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Poor Prognosis ◽  
Small Cell ◽  
Clinical Grade ◽  
Small Cell Lung ◽  
Immunohistochemistry Staining ◽  
Kaplan Meier ◽  
Nsclc Patients ◽  
Low Expression

Abstract Background:Voltage-gated sodium channels β subunits 4 (SCN4B), a tumor suppressor, was previously reported to be associated with DNA methylation and poor prognosis in multiple cancers except lung cancer. This study aimed to explore whether the low expression of SCN4B was correlated with DNA methylation and clinical prognosis in non-small cell lung cancer (NSCLC) . Methods:The gene expression profiles (GDS3837and GSE50081) were extracted from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) analysis was performed to explore the expression of SCN4B in NSCLC tissue compared with normal tissue, with the cut-off value p < 0.05 and the absolute value of the log2 fold change ≥ 1.5. Immunohistochemistry staining was used to validated its expression using The Human Protein Atlas database. And MPRESS was used to analysis the relations of SCN4B expression between DNA methylation. Then, the Fisher exact and Wilcoxon rank-sum tests were used to calculate the associations of SCN4B expression with NSCLC clinicopathological features such as clinical grade and tumor node metastasis (TNM) stage, while Kaplan–Meier survival analysis and cox regression analysis were performed to estimate the prognostic value of SCN4B expression in NSCLC. Results: Our DEGS analysis results showed a significantly decreased expression of SCN4B (p=6.5e-22) in NSCLC, which were validated by immunohistochemistry staining. Besides, this decreasing trend continued as the clinical grade and T stage advanced (p<0.05). There was a negative correlation between the SCN4B expression and DNA promoter methylation (p<0.01). Kaplan–Meier survival analysis indicated that NSCLC patients with low expression of SCN4B had a worse prognosis than those with high expression (p < 0.004). Meanwhile, univariate and multivariate analysis indicated SCN4B expression was an independent unfavorable prognostic factor for OS in NSCLC (Hazard Ratio= 0.236, p = 0.009; Hazard Ratio=0.219, p = 0.003, respectively).Conclusions: SCN4B expression was significantly downregulated in NSCLC, which might be attributed to DNA promoter hypermethylation. The low expression of SCN4B indicated a potential unfavorable prognostic factor for NSCLC patients.

scholarly journals Relationship Between Non-small Cell Lung Cancer FDG Uptake at PET, Tumor Histology, and Ki-67 Proliferation Index

2008 ◽  
Vol 3 (9) ◽  
pp. 971-978 ◽  
Author(s):  
Hubert Vesselle ◽  
Alexander Salskov ◽  
Eric Turcotte ◽  
Linda Wiens ◽  
Rodney Schmidt ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Proliferation Index ◽  
Small Cell Lung ◽  
Ki 67 ◽  
Fdg Uptake ◽  
Tumor Histology

A Novel Anti-Apoptosis Gene: Re-expression of Survivin Messenger RNA as a Prognosis Marker in Non–Small-Cell Lung Cancers

1999 ◽  
Vol 17 (7) ◽  
pp. 2100-2100 ◽  
Author(s):  
Mariano Monzó ◽  
Rafael Rosell ◽  
Enriqueta Felip ◽  
Julio Astudillo ◽  
José Javier Sánchez ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Survivin Expression ◽  
Small Cell ◽  
Normal Lung ◽  
Gene Transcript ◽  
Rt Pcr ◽  
Small Cell Lung ◽  
Histologic Subtype ◽  
Survivin Gene ◽  
Apoptosis Inhibitor

PURPOSE: The survivin gene is a novel apoptosis inhibitor, related to the baculovirus gene, which is believed to play a pivotal role in fetal development and in cancer. We hypothesised that survivin would be expressed in tumors of patients with non–small-cell lung cancer (NSCLC), and we attempted to determine the influence of survivin re-expression on clinical outcome in patients with up to stage IIIA NSCLC who had undergone radical surgery. METHODS: We designed a reverse transcriptase polymerase chain reaction (RT-PCR) assay to study the expression of the survivin gene in 83 NSCLC tumor samples and compared the results with relevant clinical and pathologic data. RESULTS: The RT-PCR identified survivin gene transcript in 71 (85.5%) of the tumor samples and in only 10 (12%) of the paired, histopathologically normal lung samples. There was no relationship between histologic subtype (squamous v nonsquamous) and survivin gene expression. The 12 patients without survivin expression had significantly better overall survival than the 71 patients with survivin expression (P = .01 by univariate analysis; relative risk, 2.1). There was no significant correlation between survivin expression and age, sex, cigarette smoking, histologic subtype, tumor differentiation, tumor size, or the presence of mediastinal lymph node metastases in surgical specimens. CONCLUSION: The survivin gene was expressed in a vast majority of NSCLC tumors. We conclude that survivin transcript is a defining diagnostic marker for NSCLC that may also yield prognostic information and, as an apoptosis inhibitor, be an important target in cancer therapy.

scholarly journals Forkhead box 1 expression is upregulatedin non-small cell lung cancer and correlateswith pathological parameters

2016 ◽  
Vol 11 (1) ◽  
pp. 220-224
Author(s):  
Chongwei Wang ◽  
Chongbang Wang ◽  
Shufang Duan
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Node Metastasis ◽  
Forkhead Box ◽  
Nsclc Patients

AbstractObjectives: As the member of the Fox family of transcription factors, Forkhead box M1 (FoxM1) is known to be critical in pathogenesis and development of many solid tumors. However, the clinical value and expression pattern in non-small cell lung cancer (NSCLC) is still poorly understood. Methods: In this study, real-time PCR was mainly applied to examine the gene expression levels of FoxM1 in 120 pairs of clinical NSCLC tissues, which were classified into different groups according to smoking status, lymph node metastasis, and tumor grade. By utilizing the online Kaplan-Meier plotter, overall survival analysis was performed to study the correlation between FoxM1 expression and prognosis of lung cancer (LC) patients. Afterwards, the correlation of FoxM1 gene expression and the clinical pathological parameters was examined by κ2 test in these 120 NSCLC patients. Results: FoxM1 was found to be aberrantly upregulated in NSCLC patients, and its overexpression was correlated to groups designated as smokers, cases of positive lymph node metastasis and cases of advanced tumor grades. Online survival analysis showed that high expression of FoxM1 predicted shorter overall survival of NSCLC patients. Additionally, FoxM1 upregulation was statistically correlated with positive smoking history, lymph node metastasis and higher tumor grades. Conclusion: FoxM1 is overexpressed in cancerous tissues and is associated with the poor prognosis of NSCLC patients. Our results provide insights into the utility of FoxM1 as an important biomarker and prognostic factor for NSCLC.

Upregulation of the Anti-Apoptotic Protein, Survivin, in Hematopoietic Cells in Sickle Cell Anemia and Effects of Hydroxyurea Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1532-1532
Author(s):  
Carolina Lanaro ◽  
Carla Fernanda Franco-Penteado ◽  
Mariana R. B. Mello ◽  
Kleber Yotsumoto Fertrin ◽  
Marcos André C Bezerra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Sickle Cell Anemia ◽  
Survivin Expression ◽  
Erythroid Differentiation ◽  
Mrna Levels ◽  
Gene Expressions ◽  
Protein Levels ◽  
Survivin Protein ◽  
Inflammatory State

Abstract Abstract 1532 Poster Board I-555 Survivin (BIRC5) is a member of the inhibitors of apoptosis family implicated in both prevention of cell death and control of mitosis. Although the actions of survivin in control of cancer cell division and apoptosis have been studied, its role in nonneoplastic diseases is not elucidated. Chronic inflammation is associated with STAT-3 upregulation, which can induce survivin production. Sickle cell anemia (SCA) has been characterized as a chronic inflammatory state and growing evidence indicates that inflammatory stress within the microvasculature may play a significant role in the vasoocclusion that is characteristic of SCA. Long-term treatment with hydroxyurea (HU) has been shown to reduce the production of inflammatory cytokines in SCA patients and leukocyte number. Since enhanced survivin expression has been reported in leukocytes under inflammatory conditions, and during hematopoietic cell survival and proliferation, the aim of this study was to investigate changes in survivin levels during erythroid differentiation, and determine expression in neutrophils (NS), mononuclear cells (MC) and red blood cell (RBC) in steady-state SCA patients (n≥10), SCA patients on HU therapy (n≥16), and healthy controls (HC, n≥5). Survivin and STAT-3 gene expression were determined by qRT-PCR analysis in primary human erythroblasts cultures for 7, 10 and 13 days and leukocytes separated from peripheral blood samples. Survivin protein expression was determined by flow cytometry with survivin-specific antibodies. Survivin gene expression was significantly increased during erythroid differentiation, but survivin mRNA levels showed similar patterns between SCA and HC (7d: 0.8±0.1 × 0.7±0.08; 10d: 1.7±0.3 × 1.6±0.2; 13d: 2.2± 0.27 × 1.8±0.19,U.A.,P>0.05,respectively). However, protein levels of survivin in mature RBC (glicophorin A +) was significantly higher in SCA patients compared to HC (41.90± 2.9 × 25.76±1.9, P=0.0006, respectively). BIRC-5 gene expression in MC was significantly higher in SCA patients compared to HC (0.9±0.1 × 0.5±0.2, P=0.04, respectively). Survivin protein levels in MC from SCA was significantly increased to compared to HC (51.7±3.2 × 39.7±1.7, MFI, P=0.01,respectively). Survivin protein levels are elevated in NS of SCA patients compared to HC (28.4±1.6 × 21.9±1.5, MFI, P=0.02,respectively). No significant alterations in the mRNA levels of the gene encoding STAT-3 were found during erythroid differentiation (7d: 1.1±0.04 × 1.1±0.08; 10d: 0.6±0.07 × 0.8±0.08; 13d: 0.6±0.07 × 0.9±0.1, P>0.05,respectively) or MC cells (1.2±0.1 × 1.1± 0.1, P>0.05,respectively) in SCA patients compared to HC. Patients on HU therapy demonstrated lower survivin MC gene expressions and protein levels compared to non-treated patients (0.6±0.3 × 0.9±0.1; 37.9±1.5 × 51.7±3.3, P=0.02; P<0.0001,respectively), but no difference was shown in STAT-3 gene expressions (1.1±0.04 × 1.2 ±0.1, respectively). Survivin protein levels were not significantly different in NS and RBC in patients on HU therapy compared to SCA (27.1±1.8 × 28.4± 1.6; 45.9± 3.2× 41.9± 2.9, MFI, P>0.05, respectively). Our data showed that survivin gene and protein expression are upregulated in MC in SCA patients, independently of STAT-3 expression. In addition, a high protein expression was observed in NS and RBC in these patients. HU therapy was associated with lower survivin expression in MC, but not NS and RBC, indicating that the beneficial effect that HU has on the inflammatory state, may participate in the reduced levels of survivin. In conclusion, the exact importance of survivin in SCA vasooclusion is not clear, but data indicates a high expression of this protein in leukocytes and RBC of SCA patients and may imply a role for this protein in leukocytosis and RBC proliferation in SCA. Disclosures No relevant conflicts of interest to declare.

Association of tumor-specific GPR87 overexpression with poor prognosis in non-small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22108-e22108
Author(s):  
Kazuhito Nii ◽  
Dage Liu ◽  
Yoshimasa Tokunaga ◽  
Xia Zhang ◽  
Shinya Ishikawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Human Tumor ◽  
Small Cell ◽  
Proliferation Index ◽  
Small Cell Lung ◽  
Ki 67

e22108 Background: GPR87 is a member of G-protein-coupled receptors (GPCRs). Recently, GPR87 was suggested to contribute to the viability of human tumor cells, and the overexpression of GPR87 mRNA was found in many malignant tumors including lung cancer. However, the clinical significance of GPR87 expression in non-small cell lung cancer (NSCLC) has not been well studied. Methods: 127 NSCLC patients who underwent surgery from 1999 to 2004 were investigated. There were 59 adenocarcinomas, 55 squamous cell carcinomas and 13 others. The intratumoral expression of GPR87 was evaluated by immunohistochemistry. The Ki-67 proliferation index was also evaluated. Results: A tumor-specific expression of GPR87 was found in NSCLC in comparison with the surrounding normal tissue. Fifty-nine tumors (46.5%) were found to be high-GPR87 tumors. The high-GPR87 tumors were more frequently found in squamous cell carcinoma than in adenocarcinoma (60.0% versus 37.3%, p=0.02). Regarding the tumor proliferation, the Ki-67 index was significantly higher in high-GPR87 tumors than in low-GPR87 tumors (p=0.04). There was a tendency that the overall survival was worse in patients with high-GPR87 tumors than in low-GPR87 tumors (p=0.22). For the patients with adenocarcinoma, the overall survival was significantly worse in patients with high-GPR87 tumors than in low-GPR87 tumors (p=0.04). Conclusions: GPR87 expression may become a poor prognostic predictor for patient with NSCLC, especially for those with adenocarcinoma. GPR87 may contribute to the cell viability by promoting cell proliferation, has a potential to become a novel therapeutic target for cancer treatment.

Analysis of a profile of lipid metabolism genes in advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20619-e20619
Author(s):  
Maria Merino ◽  
Lara Fernández ◽  
Ana Ramirez de Molina ◽  
Juan Moreno ◽  
Gonzalo Colmenarejo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Lipid Metabolism ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Gene Profile ◽  
Poor Survival ◽  
Nsclc Patients

e20619 Background: Non- small cell lung cancer (NSCLC) is one of the tumors with the highest mortality rate. The underlying metabolic alterations involved in its carcinogenesis are becoming more interesting. According to this, the analysis of the dysregulation of genes involved in lipid metabolism (LM) is subject to a growing research. To evaluate a profile of genes involved in lipid metabolism in NSCLC, we analyzed the correlation of this gene expression profile with different clinical-pathological variables. Methods: We performed a retrospective analysis of 22 genes related to LM in samples of NSCLC as well as clinical-pathological features. Advanced NSCLC patients enrolled from 2008 through 2015 were included. Clinical and pathological data were collected from medical reports. This study was approved in our ethical committee and all patients signed the consent inform. Samples were deparaffinated and RNA was extracted using RNeasy FFPE Kit (Qiagen Gmbh, Germany). A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software (Integromics Inc., Madison, USA) was used to detect and determine the quality control and differential expression analyses of data. Quantification of gene expression was calculated with the 2–ΔCt method. The Kaplan–Meier method was used for survival probabilities, and the log-rank test was to test differences between subgroups. Results: Ninety patients with advanced NSCLC were included. Median age was 64, 68/90 (75%) were male; 46/90 (51%) were ECOG 1; 68/90 (75%) adenocarcinoma vs 22/90 (24%) squamous; 47/90 (52%) smokers and 34% former smokers; metformine intake was presented in 9/90 (10%) and statins 24/90 (27%). In retrospective RT-PCR analysis including a lipid metabolism gene profile of 22 genes, we obtained an overexpression of 2 genes (an Acyl-CoA sintetase and a adipocine encoding gene). They were significantly correlated with overall poor survival in the multivariate analysis (table). These results were confirmed in an in silico validation using 994 NSCLC patients from TCGA study. Conclusions: This is the first study demonstrating a significant relation with a poor survival between a metabolic lipid gene profile expression and survival in advanced non- small cell lung cancer [Table: see text]

scholarly journals Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer

2015 ◽  
Vol 49 (3) ◽  
pp. 250-255 ◽  
Author(s):  
Adem Karaman ◽  
Irmak Durur-Subasi ◽  
Fatih Alper ◽  
Omer Araz ◽  
Mahmut Subasi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Negative Correlation ◽  
Small Cell ◽  
Proliferation Index ◽  
Tissue Sampling ◽  
Small Cell Lung ◽  
Ki 67 ◽  
The Mean

Abstract Background. The primary objective of the study was to evaluate the association between the minimum apparent diffusion coefficient (ADCmin) and Ki-67, an index for cellular proliferation, in non-small cell lung cancers. Also, we aimed to assess whether ADCmin values differ between tumour subtypes and tissue sampling method. Methods. The patients who had diffusion weighted magnetic resonance imaging (DW-MRI) were enrolled retrospectively. The correlation between ADCmin and the Ki-67 index was evaluated. Results. Ninety three patients, with a mean age 65 ± 11 years, with histopathologically proven adenocarcinoma and squamous cell carcinoma of the lungs and had technically successful DW-MRI were included in the study. The numbers of tumour subtypes were 47 for adenocarcinoma and 46 for squamous cell carcinoma. There was a good negative correlation between ADCmin values and the Ki-67 proliferation index (r = −0.837, p < 0.001). The mean ADCmin value was higher and the mean Ki-67 index was lower in adenocarcinomas compared to squamous cell carcinoma (p < 0.0001). There was no statistical difference between tissue sampling methods. Conclusions. Because ADCmin shows a good but negative correlation with Ki-67 index, it provides an opportunity to evaluate tumours and their aggressiveness and may be helpful in the differentiation of subtypes non-invasively.

Sign in / Sign up

Export Citation Format

Share Document