scholarly journals Identification of Prognostic Gene Biomarkers in Non-Small Cell Lung Cancer Progression by Integrated Bioinformatics Analysis

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1200
Author(s):  
Panagiotis Giannos ◽  
Konstantinos S. Kechagias ◽  
Annamaria Gal
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Transcription Factors ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Bioinformatics Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

The progression of non-small cell lung cancer (NSCLC) is linked to epithelial-mesenchymal transition (EMT), a biologic process that enables tumor cells to acquire a migratory phenotype and resistance to chemo- and immunotherapies. Discovery of novel biomarkers in NSCLC progression is essential for improved prognosis and pharmacological interventions. In the current study, we performed an integrated bioinformatics analysis on gene expression datasets of TGF-β-induced EMT in NSCLC cells to identify novel gene biomarkers and elucidate their regulation in NSCLC progression. The gene expression datasets were extracted from the NCBI Gene Expression Omnibus repository, and differentially expressed genes (DEGs) between TGF-β-treated and untreated NSCLC cells were retrieved. A protein-protein interaction network was constructed and hub genes were identified. Functional and pathway enrichment analyses were conducted on module DEGs, and a correlation between the expression levels of module genes and survival of NSCLC patients was evaluated. Prediction of interactions of the biomarker genes with transcription factors and miRNAs was also carried out. We described four protein clusters in which DEGs were associated with ubiquitination (Module 1), regulation of cell death and cell adhesions (Module 2), oxidation-reduction reactions of aerobic respiration (Module 3) and mitochondrial translation (Module 4). From the module genes, we identified ten prognostic gene biomarkers in NSCLC. Low expression levels of KCTD6, KBTBD7, LMO7, SPSB2, RNF19A, FOXA2, DHTKD1, CDH1 and PDHB and high expression level of KLHL25 were associated with reduced overall survival of NSCLC patients. Most of these biomarker genes were involved in protein ubiquitination. The regulatory network of the gene biomarkers revealed their interaction with tumor suppressor miRNAs and transcription factors involved in the mechanisms of cancer progression. This ten-gene prognostic signature can be useful to improve risk prediction and therapeutic strategies in NSCLC. Our analysis also highlights the importance of deregulation of ubiquitination in EMT-associated NSCLC progression.

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 Clinical Implication of N6-Methylandenosine-Related lncRNAs in Non-Small Cell Lung Cancer

2021 ◽  
Author(s):  
Wenjing Xiao ◽  
Wei Geng ◽  
Juanjuan Xu ◽  
Qi Huang ◽  
Jinshuo Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Low Risk ◽  
Small Cell Lung ◽  
Prognosis Prediction ◽  
Chemotherapeutic Sensitivity ◽  
Nsclc Patients

Abstract Background: Non-small-cell lung cancer (NSCLC) represents the leading cause of cancer-related deaths worldwide and is highly heterogeneous. The N6-methyladenosine (m6A) RNA, a vital contributor to the outcomes of cancer, can modify long non-coding RNAs (lncRNAs), thereby influencing the transcript stability, gene expression, and serving a wide array of biological functions. However, the role of m6A-related lncRNAs in NSCLC remains largely unknown. Methods: We identified a group of m6A-related lncRNAs (m6ARLncRNAs) by using co-expression analysis in 1835 NSCLC patients from The Cancer Genome Atlas (TCGA) (N=1145) and Gene Expression Omnibus (GEO) (N=690) datasets. We employed consensus unsupervised clustering analysis to explore molecular patterns based on the expression of m6ARLncRNAs. Then we filtered m6ARLncRNAs by Cox regression and LASSO regression to construct a m6ARLncRNAs signature (m6ARLncSig) and further evaluated m6ARLncSig with external and experimental validation by using qRT-PCR. We analyzed the correlation between m6ARLncSig scores groups with clinical features, chemotherapeutic sensitivity and radiotherapeutic response. Finally, we established a nomogram for prognosis prediction in patients with LUAD and validated it in the testing set and the entire TCGA dataset. Results: We constructed a m6ARLncSig for prognosis prediction of patients consisting of 12 m6ARLncRNAs. The m6ARLncSig divided patients into a high-risk group and a low-risk one, which had significantly different OS and could independently predict the prognosis of patients. Meanwhile, we revealed that patients in the high- and low-risk groups differed in tumor-infiltrating immune cells, and chemotherapeutic sensitivity, and biological pathways. Of note, we found that m6ARLncSig was associated with age, tumor stage, and radiotherapeutic response, indicating they were clinically relevant. Conclusions: Our study demonstrated that m6ARLncSig could act as a potential biomarker for evaluating the prognosis and therapeutic efficacy in NSCLC patients.

scholarly journals The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC)

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1361
Author(s):  
Ping-Chih Hsu ◽  
Cheng-Ta Yang ◽  
David M. Jablons ◽  
Liang You
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Intracellular Signaling ◽  
Small Cell ◽  
Small Cell Lung ◽  
Intrinsic Resistance ◽  
Nsclc Patients

The advancement of new therapies, including targeted therapies and immunotherapies, has improved the survival of non-small-cell lung cancer (NSCLC) patients in the last decade. Some NSCLC patients still do not benefit from therapies or encounter progressive disease during the course of treatment because they have intrinsic resistance, acquired resistance, or lack a targetable driver mutation. More investigations on the molecular biology of NSCLC are needed to find useful biomarkers for current therapies and to develop novel therapeutic strategies. Src is a non-receptor tyrosine kinase protein that interacts with cell surface growth factor receptors and the intracellular signaling pathway to maintain cell survival tumorigenesis in NSCLC. The Yes-associated protein (YAP) is one of the main effectors of the Hippo pathway and has been identified as a promoter of drug resistance, cancer progression, and metastasis in NSCLC. Here, we review studies that have investigated the activation of YAP as mediated by Src kinases and demonstrate that Src regulates YAP through three main mechanisms: (1) direct phosphorylation; (2) the activation of pathways repressing Hippo kinases; and (3) Hippo-independent mechanisms. Further work should focus on the efficacy of Src inhibitors in inhibiting YAP activity in NSCLC. In addition, future efforts toward developing potentially reasonable combinations of therapy targeting the Src–YAP axis using other therapies, including targeted therapies and/or immunotherapies, are warranted.

scholarly journals A Case of Non-Small Cell Lung Cancer with Possible “Disease Flare” on Nivolumab Treatment

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Shotaro Chubachi ◽  
Hiroyuki Yasuda ◽  
Hidehiro Irie ◽  
Koichi Fukunaga ◽  
Katsuhiko Naoki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Disease Flare ◽  
Significant Efficacy ◽  
Clinically Significant ◽  
Nsclc Patients

Background. Recent clinical trials proven the clinically significant efficacy and tolerability of nivolumab, a programmed death 1 (PD-1) inhibitor, in previously treated patients with non-small cell lung cancer (NSCLC). Case Presentation. Here, we describe the case of a patient who experienced possible “disease flare” immediately after initiation of nivolumab treatment. A 54-year-old man was diagnosed with Stage IIB (T2N1M0) lung adenocarcinoma. After 7 years from recurrence, 10th line chemotherapy, nivolumab, was initiated. Six weeks later, after 3 cycles of nivolumab treatment, rapid lung cancer progression was observed with an increase in the size of the primary lesion, multiple novel nodules on both lungs, and multiple novel brain metastases. Conclusion. We believe that physicians should be made aware that, in a subset of NSCLC patients, disease flare might occur on nivolumab treatment.

scholarly journals miR-152/TNS1 axis inhibits non-small cell lung cancer progression through Akt/mTOR/RhoA pathway

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Jinjin Duan ◽  
Li Wang ◽  
Liqun Shang ◽  
Shumei Yang ◽  
Hua Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
Nsclc Patients ◽  
Related Proteins

Abstract Aim: The purpose of the present study was to explore the function and mechanism of tensin 1 (TNS1) in non-small cell lung cancer (NSCLC) progression. Methods: The expression of TNS1 in NSCLC cells and tissues was assessed by RT-PCR and Western blot. Besides, Kaplan–Meier survival analysis was recruited to explore the association between TNS1 and NSCLC. Cell growth was analyzed by MTT and flow cytometry assay, while cell metastasis was determined by wound healing and transwell assays. The targeting relationship between TNS1 and miR-152 was assessed by luciferase activity assays. And Western blot was employed to determine the expression of related proteins of Akt/mTOR/RhoA pathway. Results: TNS1 level was boosted in NSCLC cells and tissues, related to the prognosis of NSCLC patients. Furthermore, it was proved that TNS1 promoted the growth and metastasis of NSCLC cells via Akt/mTOR/RhoA pathway. And miR-152 targeted TNS1 to affect the progression of NSCLC. Conclusion: miR-152/TNS1 axis inhibits the progression of NSCLC by Akt/mTOR/RhoA pathway.

Comparative Proteomics and Bioinformatics Analysis of Tissue from Non-Small Cell Lung Cancer Patients

2017 ◽  
Vol 14 (1) ◽  
pp. 58-77
Author(s):  
Sevgi Gezici ◽  
Mehmet Ozaslan ◽  
Gurler Akpinar ◽  
Murat Kasap ◽  
Maruf Sanli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Bioinformatics Analysis ◽  
Comparative Proteomics ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients
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