scholarly journals Lipid metabolic transcriptome-wide profile and signature of lung adenocarcinoma

2020 ◽  
Author(s):  
Jinyou Li ◽  
Qiang Li ◽  
Zhenyu Su ◽  
Qi Sun ◽  
Yong Zhao ◽  
...  

Abstract Background: Lung cancer is the cancer with high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. The disorder of lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on diagnosis and prognostic biomarkers of LUAD. Methods: In this study, we performed an expression analysis of 1045 lipid metabolism-related genes between LUAD tumors and normal tissues from the TCGA-LUAD cohort. The interaction network of differential expression genes (DEGs) was constructed to identify. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram, and the model was validated by another cohort (GSE13213). Results: Finally, a total of 217 lipid metabolism-related DEGs were detected in LUAD. They were significantly enriched in glycerophospholipid and steroid metabolism . Then we identified 6 hub genes through network and cytoHubba, including INS , LPL , HPGDS , DGAT1 , UGT1A6 , and CYP2C9 . The high expression of CYP2C9 , UGT1A6 , and INS , whereas low expressions of DGAT1 , HPGDS , and LPL , were associated with worse OS for 719 LUAD patients. Our model found that the high-risk score group had a worse OS, and the validated cohort had the same result. Conclusion: This study constructed a signature of six lipid metabolic genes, which was significantly associated with the diagnosis and prognosis of LUAD patients. The gene signature can be used as a biomarker for LUAD in the term of lipid metabolic.

2020 ◽  
Author(s):  
Jinyou Li ◽  
Qiang Li ◽  
Zhenyu Su ◽  
Qi Sun ◽  
Yong Zhao ◽  
...  

Abstract Background: Lung cancer is the cancer with high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. The disorder of lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on diagnosis and prognostic biomarkers of LUAD. Methods: In this study, we performed an expression analysis of 1045 lipid metabolism-related genes between LUAD tumors and normal tissues from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differential expression genes (DEGs) was constructed to identify. The association between hub genes and overall survival was evaluated and formed a model to predict the prognosis of LUAD using a nomogram, and the model was validated by another cohort (GSE13213). Results: Finally, a total of 217 lipid metabolism-related DEGs were detected in LUAD. They were significantly enriched in Glycerophospholipid metabolism, fatty acid metabolic process, and Eicosanoid Signaling. Then we identified 6 hub genes through network and cytoHubba, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. The high expression of CYP2C9, UGT1A6, and INS, whereas low expressions of DGAT1, HPGDS, and LPL, were associated with worse overall survival (OS) for 1925 LUAD patients. Our model found that the high-risk score group had a worse OS, and the validated cohort had the same result.Conclusion: This study constructed a signature of six lipid metabolic genes, which was significantly associated with the diagnosis and prognosis of LUAD patients. The gene signature can be used as a biomarker for LUAD in the term of lipid metabolic.


2020 ◽  
Author(s):  
Jinyou Li ◽  
Qiang Li ◽  
Zhenyu Su ◽  
Qi Sun ◽  
Yong Zhao ◽  
...  

Abstract Background: Lung cancer has high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. Disordered lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on the diagnosis and prognostic biomarkers of LUAD. Methods: In this study, expression analysis of 1045 lipid metabolism-related genes was performed between LUAD tumors and normal tissues derived from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differentially expressed genes (DEGs) was constructed to identify the hub genes. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram. The model was validated by another cohort, GSE13213. Results: A total of 217 lipid metabolism-related DEGs were detected in LUAD. Genes were significantly enriched in glycerophospholipid metabolism, fatty acid metabolic process, and eicosanoid signaling. Through network analysis and cytoHubba, 6 hub genes were identified, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. High expression of CYP2C9, UGT1A6, and INS, and low expressions of DGAT1, HPGDS, and LPL, were associated with worse overall survival for 1925 LUAD patients. The model showed that the high-risk score group had a worse OS, and the validated cohort showed the same result.Conclusions: In this study, a signature of 6 lipid metabolism genes was constructed, which was significantly associated with the diagnosis and prognosis of LUAD patients. Thus, the gene signature can be used as a biomarker for LUAD.


2020 ◽  
Author(s):  
Jinyou Li ◽  
Qiang Li ◽  
Zhenyu Su ◽  
Qi Sun ◽  
Yong Zhao ◽  
...  

Abstract Background: Lung cancer has high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. A disordered lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on the diagnosis and prognostic biomarkers of LUAD. Methods: In this study, expression analysis of 1045 lipid metabolism-related genes was performed between LUAD tumors and normal tissues derived from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differentially-expressed genes (DEGs) was constructed to identify the hub genes. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram. The model was validated by another cohort, GSE13213. Results: A total of 217 lipid metabolism-related DEGs were detected in LUAD. Genes were significantly enriched in glycerophospholipid metabolism, fatty acid metabolic process, and eicosanoid signaling. Through network analysis and cytoHubba, 6 hub genes were identified, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. High expression of CYP2C9, UGT1A6, and INS, and low expressions of DGAT1, HPGDS, and LPL, were associated with a worse overall survival for 1925 LUAD patients. The model showed that the high-risk score group had a worse OS, and the validated cohort showed the same result. Conclusions: In this study, a signature of 6 lipid metabolism genes was constructed, which was significantly associated with the diagnosis and prognosis of LUAD patients. Thus, the gene signature can be used as a biomarker for LUAD.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinyou Li ◽  
Qiang Li ◽  
Zhenyu Su ◽  
Qi Sun ◽  
Yong Zhao ◽  
...  

Abstract Background Lung cancer has high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. Disordered lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on the diagnosis and prognostic biomarkers of LUAD. Methods In this study, expression analysis of 1045 lipid metabolism-related genes was performed between LUAD tumors and normal tissues derived from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differentially expressed genes (DEGs) was constructed to identify the hub genes. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram. The model was validated by another cohort, GSE13213. Results A total of 217 lipid metabolism-related DEGs were detected in LUAD. Genes were significantly enriched in glycerophospholipid metabolism, fatty acid metabolic process, and eicosanoid signaling. Through network analysis and cytoHubba, 6 hub genes were identified, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. High expression of CYP2C9, UGT1A6, and INS, and low expressions of DGAT1, HPGDS, and LPL, were associated with worse overall survival for 1925 LUAD patients. The model showed that the high-risk score group had a worse OS, and the validated cohort showed the same result. Conclusions In this study, a signature of 6 lipid metabolism genes was constructed, which was significantly associated with the diagnosis and prognosis of LUAD patients. Thus, the gene signature can be used as a biomarker for LUAD.


2020 ◽  
Author(s):  
Jinyou Li ◽  
Qiang Li ◽  
Zhenyu Su ◽  
Qi Sun ◽  
Yong Zhao ◽  
...  

Abstract Background Lung cancer is a worldwide cancer with high morbidity and mortality. More and more evidence shows that the disorder of lipid metabolism is the key to the development of cancer, and analysis of lipid-related genes may lead to diagnosis and prognostic biomarkers related to lung cancer. Methods In this study, we performed the differentially expressed analysis of 1045 lipid metabolism-related genes between LUAD tumors and normal tissues in the TCGA-LUAD cohort. Then the bioinformatic analysis of DEGs was showed. PPI networks and cytoHubba APP determine hub genes. The association between hub genes and overall survival was evaluated by Kaplan-Meier Plotter. To predict the prognosis of LUAD patients, a nomogram was built, the nomogram was validated by another cohort (GSE13213). Results Finally, a total of 217 lipid metabolism-related DEGs were detected in LUAD. They were significantly enriched in Glycerophospholipid metabolism, fatty acid metabolic process, and Eicosanoid Signaling. Then we identified 6 hub genes through PPI network and cytoHubba, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. The high expression of CYP2C9, UGT1A6, and INS, whereas low expressions of DGAT1, HPGDS, and LPL, were associated with worse OS for 1925 LUAD patients. Based on the nomogram, we found that the high-risk score group had a worse OS, and the validated cohort had the same result. Conclusion In conclusion, we generated a lipid metabolic transcriptome-wide profile of LUAD patients and found that significant lipid metabolic pathways were correlated with the LUAD. Furthermore, we constructed a signature of six lipid metabolic genes, which significantly associated with diagnosis and prognosis of LUAD patients. The gene signature can be used as a biomarker for LUAD.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yi He ◽  
Ruijie Liu ◽  
Mei Yang ◽  
Wu Bi ◽  
Liuyin Zhou ◽  
...  

Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It’s imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.


2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110210
Author(s):  
Hui Sun ◽  
Li Ma ◽  
Jie Chen

Objective Uterine carcinosarcoma (UCS) is a rare, aggressive tumour with a high metastasis rate and poor prognosis. This study aimed to explore potential key genes associated with the prognosis of UCS. Methods Transcriptional expression data were downloaded from the Gene Expression Profiling Interactive Analysis database and differentially expressed genes (DEGs) were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses using Metascape. A protein–protein interaction network was constructed using the STRING website and Cytoscape software, and the top 30 genes obtained through the Maximal Clique Centrality algorithm were selected as hub genes. These hub genes were validated by clinicopathological and sequencing data for 56 patients with UCS from The Cancer Genome Atlas database. Results A total of 1894 DEGs were identified, and the top 30 genes were considered as hub genes. Hyaluronan-mediated motility receptor (HMMR) expression was significantly higher in UCS tissues compared with normal tissues, and elevated expression of HMMR was identified as an independent prognostic factor for shorter survival in patients with UCS. Conclusions These results suggest that HMMR may be a potential biomarker for predicting the prognosis of patients with UCS.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12140
Author(s):  
Bing Chen ◽  
Shiya Zheng ◽  
Feng Jiang

Background Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer. Studies have found that miR-1293 is related to the survival of LUAD patients. Unfortunately, its role in LUAD remains not fully clarified. Methods miR-1293 expression and its association with LUAD patients’ clinical characteristics were analyzed in TCGA database. Also, miR-1293 expression was detected in LUAD cell lines. Cell viability, migration, invasion and expression of MMP2 and MMP9 were measured in LUAD cells following transfection with miR-1293 mimic or antagomir. Phosphoglucomutase (PGM) 5 was identified to be negatively related to miR-1293 in LUAD patients in TCGA database, and their association was predicated by Targetscan software. Hence, we further verified the relationship between miR-1293 and PGM5. Additionally, the effect and mechanism of miR-1293 were validated in a xenograft mouse model. Results We found miR-1293 expression was elevated, but PGM5 was decreased, in LUAD patients and cell lines. Higher miR-1293 expression was positively related to LUAD patients’ pathologic stage and poor overall survival. miR-1293 mimic significantly promoted, whereas miR-1293 antagomir suppressed the viability, migration, invasion, and expression of MMP2 and MMP9 in LUAD cells. PGM5 was a target of miR-1293. Overexpression of PGM5 abrogated the effects of miR-1293 on the malignant phenotypes of LUAD cells. Administration of miR-1293 antagomir reduced tumor volume and staining of Ki-67 and MMP9, but elevated PGM5 expression in vivo. Conclusions miR-1293 promoted the proliferation, migration and invasion of LUAD cells via targeting PGM5, which indicated that miR-1293 might serve as a potential therapeutic target for LUAD patients.


2021 ◽  
Author(s):  
Q Shi ◽  
Z Meng ◽  
XX Tian ◽  
YF Wang ◽  
WH Wang

Aims: We aim to provide new insights into the mechanisms of hepatocellular carcinoma (HCC) and identify key genes as biomarkers for the prognosis of HCC. Materials & methods: Differentially expressed genes between HCC tissues and normal tissues were identified via the Gene Expression Omnibus tool. The top ten hub genes screened by the degree of the protein nodes in the protein–protein interaction network also showed significant associations with overall survival in HCC patients. Results: A prognostic model containing a five-gene signature was constructed to predict the prognosis of HCC via multivariate Cox regression analysis. Conclusion: This study identified a novel five-gene signature ( CDK1, CCNB1, CCNB2, BUB1 and KIF11) as a significant independent prognostic factor.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Fei Tian ◽  
Rui Li ◽  
Zhenzhu Chen ◽  
Yanting Shen ◽  
Jiafeng Lu ◽  
...  

Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer.


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