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 ◽  
...  

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]

2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
feng wu

Abstract Background: LncRNA SNHG10 has been reported to be an oncogenic lncRNA in liver cancer. However, its roles in non-small cell lung cancer (NSCLC) remains unknown. Methods: Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. RT-qPCR was used to detect the expression of SNHG10 and miR-21 in tissues. Overexpression experiments were used to evaluate the interaction between SNHG10 and miR-21 in NSCLC cells. CCK-8 assay was used to detect the cell proliferation. Results: We observed the expression of SNHG10 was down-regulated in non-small cell lung cancer (NSCLC) compared with that in non-tumor tissues. Moreover, we found that high expression levels of SNHG10 predicted favorable survival of NSCLC patients, and the expression of miR-21 were increased in NSCLC and inversely correlated with SNHG10 expression. In NSCLC cells, overexpression of SNHG10 resulted in increased miR-21 gene methylation and decreased miR-21 expression. Moreover, overexpression of SNHG10 attenuated the enhancing effect of miR-21 overexpression on cell proliferation. Conclusions: SNHG10 may involve in NSCLC cell proliferation by regulating the miR-21 gene methylation.


2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
Feng Wu

Abstract LncRNA SNHG10 has been characterized as an oncogenic lncRNA in liver cancer. By analyzing TCGA dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC), indicating its involvement in this disease. We then analyzed the role of SNHG10 in NSCLC.Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. Expression of SNHG10 and miR-21 in tissues was determined by RT-qPCR. Overexpression of SNHG10 or miR-21 in NSCLC cells was achieved and the interaction between them was analyzed. Cell proliferation was analyzed by CCK-8 assay.In this study we found that SNHG10 is downregulated in cancer tissues of NSCLC patients included in this study. High expression level of SNHG10 predicted favorable survival of NSCLC patients. Levels of miR-21 expression were increased in NSCLC and inversely correlated with SNHG10. In NSCLC cells, SNHG10 overexpression led to increased miR-21 gene methylation and decreased miR-21 expression level. In cell proliferation assay, SNHG10 overexpression attenuated the enhancing effect of miR-21 overexpression on cell proliferation. SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival. It may downregulated miR-21 through methylation to suppress cancer cell proliferation.


2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
feng wu

Abstract Background: LncRNA SNHG10 has been reported to be an oncogenic lncRNA in liver cancer. However, its roles in non-small cell lung cancer (NSCLC) remains unknown. Methods: Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. RT-qPCR was used to detected the expression of SNHG10 and miR-21 in tissues. Overexpression experiments were used to evaluate the interaction between SNHG10 or miR-21 in NSCLC cells. CCK-8 assay was used to detect the cell proliferation. Results: We observed the expression of SNHG10 was down-regulated in non-small cell lung cancer (NSCLC) compared with that in non-tumor tissues. Moreover, we found that high expression levels of SNHG10 predicted favorable survival of NSCLC patients, and the expression of miR-21 were increased in NSCLC and inversely correlated with SNHG10 expression. In NSCLC cells, overexpression of SNHG10 resulted in increased miR-21 gene methylation and decreased miR-21 expression. Moreover, overexpression of SNHG10 attenuated the enhancing effect of miR-21 overexpression on cell proliferation. Conclusions: SNHG10 may involve in NSCLC cell proliferation by regulating the miR-21 gene methylation.


2021 ◽  
Author(s):  
Wenjing Xiao ◽  
Wei Geng ◽  
Juanjuan Xu ◽  
Qi Huang ◽  
Jinshuo Fan ◽  
...  

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.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
Feng Wu

Abstract Background LncRNA SNHG10 has been reported to be an oncogenic lncRNA in liver cancer. However, its roles in non-small cell lung cancer (NSCLC) remains unknown. Methods Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. RT-qPCR was used to detect the expression of SNHG10 and miR-21 in tissues. Overexpression experiments were used to evaluate the interaction between SNHG10 and miR-21 in NSCLC cells. CCK-8 assay was used to detect the cell proliferation. Results We observed the expression of SNHG10 was down-regulated in non-small cell lung cancer (NSCLC) compared with that in non-tumor tissues. Moreover, we found that high expression levels of SNHG10 predicted favorable survival of NSCLC patients, and the expression of miR-21 were increased in NSCLC and inversely correlated with SNHG10 expression. In NSCLC cells, overexpression of SNHG10 resulted in increased miR-21 gene methylation and decreased miR-21 expression. Moreover, overexpression of SNHG10 attenuated the enhancing effect of miR-21 overexpression on cell proliferation. Conclusions SNHG10 may involve in NSCLC cell proliferation by regulating the miR-21 gene methylation.


Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1200
Author(s):  
Panagiotis Giannos ◽  
Konstantinos S. Kechagias ◽  
Annamaria Gal

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.


2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
feng wu

Abstract LncRNA SNHG10 has been characterized as an oncogenic lncRNA in liver cancer. By analyzing TCGA dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC), indicating its involvement in this disease. We then analyzed the role of SNHG10 in NSCLC. Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. The expression of SNHG10 and miR-21 in tissues were determined by RT-qPCR. Overexpression of SNHG10 or miR-21 in NSCLC cells was achieved and the interaction between them was evaluated. Cell proliferation was determined by CCK-8 assay. In this study we found that SNHG10 was downregulated in cancer tissues of NSCLC patients. High expression levels of SNHG10 predicted favorable survival of NSCLC patients. The expression levels of miR-21 were increased in NSCLC and inversely correlated with SNHG10. In NSCLC cells, overexpression of SNHG10 led to increased miR-21 gene methylation and decreased the expression levels of miR-21. In cell proliferation assay, overexpression of SNHG10 attenuated the enhancing effect of overexpression of miR-21 on cell proliferation. SNHG10 was downregulated in non-small cell lung cancer and predicted poor survival. It may downregulate miR-21 through methylation to suppress cancer cell proliferation.


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