scholarly journals Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Francesco Grossi ◽  
Maria Giovanna Dal Bello ◽  
Sandra Salvi ◽  
Roberto Puzone ◽  
Ulrich Pfeffer ◽  
...  
Keyword(s):  
Ribonucleotide Reductase ◽  
Thymidylate Synthase ◽  
Poor Prognosis ◽  
Microarray Dataset ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Resected Nsclc ◽  
Nsclc Patients ◽  
Gene Expression Levels

Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class IIIbeta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients.

scholarly journals Overexpression of HSP10 correlates with HSP60 and Mcl-1 levels and predicts poor prognosis in non-small cell lung cancer patients

2020 ◽  
pp. 1-10
Author(s):  
Yaoxiang Tang ◽  
Yang Yang ◽  
Jiadi Luo ◽  
Sile Liu ◽  
Yuting Zhan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Mitochondrial Protein ◽  
Small Cell ◽  
Small Cell Lung ◽  
Aberrant Expression ◽  
Resected Nsclc ◽  
Nsclc Patients

BACKGROUND: HSP60 and its partner HSP10 are members of heat shock proteins (HSPs) family, which help mitochondrial protein to fold correctly. Mcl-1 a member of the Bcl-2 family, plays a crucial role in regulation of cell apoptosis. Aberrant expression of HSP10 HSP60 and Mcl-1 is involved in the development of many tumors. OBJECTIVE: To examine the association between expression of HSP10, HSP60 and Mcl-1 and clinicopathological features of non-small cell lung cancer (NSCLC). METHODS: Tissue microarrays including 53 non-cancerous lung tissues (Non-CLT) and 354 surgically resected NSCLC were stained with anti-HSP10, anti-HSP60 and anti-Mcl-1 antibodies respectively by immunohistochemistry. RESULTS: Higher expression of HSP10, HSP60 and Mcl-1 was found in NSCLC compared with Non-CLT. Both individual and combined HSP10 and HSP60 expression in patients with clinical stage III was higher than that in stage I ∼ II. Expression of HSP10 showed a positive correlation with HSP60 and Mcl-1. Overall survival time of NSCLC patients was remarkably shorter with elevated expression of HSP10, HSP60 and Mcl-1 alone and in combination. Moreover overexpression of HSP10 and Mcl-1 was poor independent prognostic factor for lung adenocarcinoma patients. CONCLUSIONS: High expression of HSP10 HSP60 and Mcl-1 might act as novel biomarker of poor prognosis for NSCLC patients.

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 Elevated Exosome-derived Mirnas Predict Osimertinib Resistance in Non-small Cell Lung Cancer

2020 ◽  
Author(s):  
Xinying Li ◽  
Cen Chen ◽  
Zimu Wang ◽  
Jiaxin Liu ◽  
Wei Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Exosomal Mirnas ◽  
Nsclc Patients ◽  
Serum Exosomes

Abstract Background: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations will inevitably develop drug resistance after being treated with the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib. In recent years, many studies have been focusing on the ability of exosomal miRNAs secreted by tumor cells to transmit resistance information. However, the mechanism of exosome-derived miRNAs in osimertinib resistance remains unexplored.Methods: We extracted and sequenced exosomes from the supernatant of the osimertinib-resistant cell line, H1975-OR, and the sensitive cell line, H1975. The results were compared with plasma exosome sequencing before and after the appearance of drug resistance in three NSCLC clinical patients treated with oral osimertinib. Exosome-derived miRNAs that had significantly increased expression levels after osimertinib resistance were screened for expanded validation in other 64 NSCLC patients.Results: Cluster analysis of the target genes revealed that exosomal miRNAs participate in osimertinib resistance mechanisms through the activation of bypass pathways (RAS-MAPK pathway abnormality and PI3K pathway activation). Exosome-derived miR-184 (p = 0.0325) and miR-3913-5p (p = 0.0169) expression levels increased significantly after the onset of osimertinib resistance. Exosomal miR-184 was correlated with lactate dehydrogenase levels (p = 0.018). Exosomal miR-3913-5p was associated with TNM stage (p = 0.045), platelet count (p = 0.024), tumor marker carcinoembryonic antigen (p = 0.045), and distant metastases (p = 0.049), especially bone metastasis (p = 0.03). In the subgroup of patients with EGFR exon 21 L858R point mutation, miR-184 (p = 0.0104) and miR-3913-5p (p = 0.0085) derived from serum exosomes had both significantly increased expression levels. In the subgroup of T790M-positive patients, miR-3913-5p derived from serum exosomes may also be a good indicator of osimertinib resistance (p = 0.013).Conclusions: The expression levels of miR-184 and miR-3913-5p derived from exosomes in the peripheral blood of NSCLC patients could be used as biomarkers to indicate osimertinib resistance.

Increased incidence of brain metastases in ERCC1-negative NSCLC patients treated with adjuvant cisplatin-based chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7581-7581
Author(s):  
B. Besse ◽  
C. Massard ◽  
V. Haddad ◽  
F. André ◽  
A. Dunant ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Chemotherapy ◽  
Brain Metastases ◽  
Small Cell ◽  
Clinical Parameters ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Increased Risk ◽  
Metastatic Sites ◽  
Nsclc Patients

7581 Background: We have recently demonstrated that ERCC1 is a predictor of the benefit of cisplatin-based adjuvant chemotherapy in resected non-small cell lung cancer (NSCLC). Non-squamous carcinomas have an increased risk of brain metastases (BM). Since brain is considered as a sanctuary site for chemotherapy, we hypothesised that there was an increased incidence of BM in ERCC1- negative non-squamous NSCLC patients treated with adjuvant cisplatin-based chemotherapy. Methods: Incidence of BM and histo- clinical parameters were analyzed in a population of 783 patients enrolled in the IALT trial. A subgroup analysis was performed in ERCC1 negative non-squamous NSCLC patients. Results: One hundred and one patients out of 783 (13%) developed BM alone or in association with other metastatic sites. In multivariate analysis, the clinical parameters associated with the occurrence of BM were nodal status (p=0.02), histological type (p=0.001) and pleural invasion (p=0.02). There is no effect of chemotherapy on BM (HR 1.38 [0.91–2.07], p=0.13). In patients with non-squamous histology (n=335) adjuvant chemotherapy was associated with an increased risk of BM (HR=2.10, [1.01–4.32], p=0.04) for ERCC1-negative tumours whereas there was no evidence of an effect on brain metastasis for ERCC1-positive tumours (HR=1.07 [0.38–2.99] p=0.90). These 2 effects are nevertheless not different (p for interaction=0.30) possibly by lack of power in this subsample. Conclusions: This study would suggest that cisplatin-based adjuvant chemotherapy is associated with an increased risk of BM in resected NSCLC patients with chemosensitive tumors. This data, if confirmed, could provide a rationale to evaluate prophylactic strategies in this subset of patients. No significant financial relationships to disclose.

scholarly journals Expression and Diagnostic Efficacy of miR-126-5p and miR-34c-3p in Serum Extracellular Vesicles of Non-Small Cell Lung Cancer Patients

2021 ◽  
Author(s):  
Jie Zhao ◽  
Wenlu Hang ◽  
Qian Wang ◽  
Yonghong Xu
Keyword(s):  
Lung Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Small Cell Lung Cancer ◽  
Poor Prognosis ◽  
Clinical Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Node Metastasis ◽  
Nsclc Patients

Abstract Background: Non-small cell lung cancer (NSCLC) is a disease with quite grave prognosis. This study explored the diagnostic efficiency of miR-126-5p and miR-34c-3p in serum extracellular vesicles (EVs) in NSCLC patients.Methods: Serum EVs were extracted from NSCLC patients and healthy people and verified. The expression of miR-126-5p and miR-34c-3p in serum EVs were tested. Correlation of miR-126-5p and miR-34c-3p expression and diagnosis, prognosis and pathological characteristics (age, gender, tumor size, clinical stage, and lymph node metastasis) of NSCLC patients was analyzed. The downstream targets of miR-126-5p and miR-34c-3p were predicted and their roles in diagnosis and prognosis of NSCLC patients were evaluated.Results: miR-126-5p and miR-34c-3p were poorly expressed in serum EVs of NSCLC patients and their low expressions were associated with clinical stage, lymph node metastasis and prognosis of NSCLC patients and could be used as biomarkers for diagnosis. As the common target genes of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 were highly expressed in serum EVs and were associated with poor prognosis in NSCLC patients.Conclusion: Lowly expressed miR-126-5p and miR-34c-3p in serum EVs of NSCLC patients can serve as biomarkers for diagnosis and are linked with prognosis. As common targets of miR-126-5p and miR-34c-3p, LYPLA1 and CDK6 are also associated with poor prognosis in NSCLC patients.

scholarly journals The Impact of Programmed Death-Ligand 1 Expression on the Prognosis of Early Stage Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Literatures

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Shi ◽  
Shuai Zhu ◽  
Hengjuan Guo ◽  
Xiongfei Li ◽  
Shikang Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Meta Analysis ◽  
Small Cell ◽  
Cochrane Library ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Nsclc Patients

IntroductionPrevious studies have demonstrated that programmed cell death-ligand 1 (PD-L1) serves as biomarker for poor prognosis and survival in advanced-stage non-small cell lung cancer (NSCLC) patients. However, the merit of PD-L1 expression to predict the prognosis of early stage NSCLC patients who underwent complete resection remains controversial. In the present study, we performed a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in patients with early stage resected NSCLC.MethodsElectronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched until July 23 2020 for studies evaluating the expression of PD-L1 and the prognosis of resected NSCLCs. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS) were pooled and analyzed. Heterogeneity and publication bias analyses were also assessed.ResultsA total of 15 studies involving 3,790 patients were considered in the present meta-analysis. The pooled HR indicated that PD-L1 expression related to a much shorter DFS (HR = 1.56, 95% CI: 1.18–2.05, p &lt; 0.01), as well a significantly worse OS (HR = 1.68, 95% CI: 1.29–2.18, p &lt; 0.01). Furthermore, our analysis indicated that PD-L1 expression was significantly associated with gender (male vs. female: OR = 1.27, 95% CI:1.01–1.59, p = 0.038), histology (ADC vs. SCC: OR = 0.54, 95% CI:0.38–0.77, p = 0.001), TNM stage (I vs. II–III: OR = 0.45, 95% CI:0.34–0.60, p = 0.000), smoking status (Yes vs No: OR = 1.43, 95% CI:1.14–1.80, p = 0.002) and lymph node metastasis (N+ vs N−: OR = 1.97, 95% CI:1.26–3.08, p = 0.003).ConclusionsThe results of this meta-analysis suggest that PD-L1 expression predicts an unfavorable prognosis in early stage resected NSCLCs. The role of personalized anti-PD-L1/PD-1 immunotherapy in the adjuvant settings of resected NSCLC warrants further investigation.

Sign in / Sign up

Export Citation Format

Share Document