Analysis of Long Non-Coding RNA Expression Profiles in Non-Small Cell Lung Cancer

Background/Aims: Long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. However, the role of lncRNA expression in human Non-small cell lung cancer (NSCLC) biology, prognosis and molecular classification remains unknown. Methods: We established the IncRNA profile in NSCLC by re-annotation of microarrays from the Gene expression omnibus database. Quantitative real-time PCR was used to determine expression of LINC00342. Results: 6066 differentially expressed IncRNAs were identified and we found a novel IncRNA, LINC00342 was significantly up-regulated in NSCLC tissues compared with normal tissues. We confirmed the over-expression of LINC00342 in a cohort of NSCLC patients and found LINC00342 expression level was positively correlated with lymph node metastasis and TNM stages. Furthermore, in a large online database of 1942 NSCLC patients, high expression of LINC00342 indicated poor Overall survival (HR = 1.28, 95% CI: 1.13-1.45) and post progression survival (HR = 1.43, 95% CI: 1.09-1.88). Bioinformatics analyses showed that LINC00342 was co-expressed with different protein-coding genes in NSCLC and normal tissues. Additionally, gene set enrichment analyses found that PTEN and P53 pathways genes were enriched in the groups with higher LINC00342 expression level. By small interfering RNAs mediated silence of LINC00342, proliferation ability was significantly inhibited in lung cancer cell line. Conclusion: To summary, our findings indicate that a set of IncRNAs are differentially expressed in NSCLC and we characterized a novel IncRNA, LINC00342 which is significantly up-regulated in NSCLC and could be a prognostic biomarker.

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Prognostic significance of CD276 in non-small cell lung cancer

Open Medicine ◽

10.1515/med-2019-0076 ◽

2019 ◽

Vol 14 (1) ◽

pp. 805-812

Author(s):

Changgong Zhang ◽

Xuezhi Hao

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Expression Level ◽

Normal Lung ◽

Small Cell Lung ◽

Nsclc Tissue ◽

Normal Tissues ◽

Nsclc Patients

AbstractBackgroundThe expression and significance of CD276 in non-small cell lung cancer (NSCLC) was explored.MethodThe BioGPS database was used to analyze the expression level of CD276 in normal tissues. Studies on the expression of CD276 in NSCLC patients using the Oncomine database. The prognostic roles of CD276 in NSCLC was studied using the Kaplan-Meier plotter database.ResultThe BioGPS database showed CD276 expression in all the human normal tissues. Compared with normal lung tissue, CD276 gene highly expressed in NSCLC tissue at mRNA level (P<0.05). The expression level of CD276 gene was negatively correlated with overall survival (OS) of NSCLC patients. Subgroup analysis showed that CD276 expression level had a significant effect on OS of patients with lung adenocarcinoma, while in squamous cell carcinoma its expression level had no significant effect on OS.ConclusionAccording to the information mined from the tumor gene database, CD276 mRNA was found highly expressed in NSCLC tissue and the expression of CD276 has a significant impact on survival of NSCLC patients, which provides an important theoretical basis for further study of the role of CD276 in the occurrence and development of NSCLC.

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Co-expression Network and Prognosis Analyses of Pyroptosis-related Genes in Non-small Cell Lung Cancer

10.21203/rs.3.rs-627404/v1 ◽

2021 ◽

Author(s):

Zixiao Liu ◽

Xudong Liu ◽

Yu Zhang ◽

Yongjie Zhou ◽

Shuaibin Lian ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Hydrophobic Interactions ◽

Tumor Staging ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Differentially Expressed ◽

Small Cell Lung ◽

Nsclc Patients

Abstract Lung cancer is very difficult to diagnose in the its early stages because of its initial asymptomatic characteristics. In recent years, pyrolysis has been shown identified as a novel type of programmed cell death with inflammation mediated by the gasdermin family. In this study, 33 differentially-expressed pyroptosis-related genes were commonly identified in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. Tumor-related gasdermin family genes that were significantly differentially expressed in non-small cell lung cancer (NSCLC) tissues were identified by our co-expression network analysis. Among them, the mRNA level of GSDMB gene had significant impacts on tumor staging and survival rates of NSCLC patients. Therefore, this gene is a potential new therapeutic target for the treatment of NSCLC. In addition, the high expression levels of GSDMC/D were significantly correlated with the low overall survival (OS), progression-free survival (FP) and post-progression survival (PPS) of NSCLC patients. Therefore, this gene is a potential oncogene for NSCLC. Furthermore, four small molecules (erastin, cefotiam, metanephrine, and vorinostat) that could most significantly reverse the NSCLC gene expression were identified. They interacted with GSDMB proteins mainly through H-bonds and hydrophobic interactions. This study provides new therapeutic targets and prognostic makers for NSCLC patients.

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Identification of LOC338963 and AP3B2 as Potential Biomarkers for Lambert-Eaton Myasthenic Syndrome

10.21203/rs.3.rs-332560/v1 ◽

2021 ◽

Author(s):

Fei Yang ◽

Feng Jing ◽

Yang Li ◽

Shanshan Kong ◽

Shimin Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Expression Profiles ◽

Small Cell ◽

Differentially Expressed ◽

Healthy Controls ◽

Small Cell Lung ◽

Qrt Pcr ◽

Myasthenic Syndrome

Abstract Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder associated with muscle weakness and small-cell lung cancer. Here, we used microarray analysis to identify long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) that might serve as biomarkers for LEMS.Methods: Plasma lncRNA and mRNA expression profiles of three patients with paraneoplastic LEMS and three healthy controls were analyzed using Arraystar Human lncRNA Microarray v4.0. Differentially expressed lncRNAs and adjacent mRNAs were analyzed jointly, and candidates were verified in individual samples by quantitative real-time polymerase chain reaction (qRT-PCR). The identified lncRNAs and mRNAs were evaluated in nine patients with paraneoplastic LEMS, eight patients with non-tumor LEMS, and four patients with small cell lung cancer (SCLC). Results: A total of 320 lncRNAs were differentially expressed in patients with paraneoplastic LEMS compared to healthy controls (fold change >1.5, P < 0.05), and nine were further evaluated. One of the identified lncRNAS, LOC338963 (NR_031439), is known to regulated the expression of the mRNA AP3B2, and both were upregulated more than 2-fold in patients with paraneoplastic LEMS compared to healthy controls. Furthermore, qRT-PCR analysis revealed significant upregulation of LOC338963 (NR_031439) and AP3B2 expression in patients with paraneoplastic LEMS compared to those with either non-tumor LEMS (2.37- and 5.06-fold, respectively) or SCLC (4.36- and 14.97-fold, respectively).Conclusions: Plasma LOC338963 (NR_031439) and AP3B2 were found to be upregulated in LEMS and might be used as diagnostic biomarkers for this disease.

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Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.764270 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jun Liu ◽

Yi Lu ◽

Wenan Huang ◽

Zhibo He

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Prognostic Significance ◽

Small Cell ◽

Expression Level ◽

Mrna Levels ◽

Small Cell Lung ◽

Normal Tissues ◽

Apoptosis Protein

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.

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LncRNA SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival

10.21203/rs.3.rs-20439/v1 ◽

2020 ◽

Author(s):

Meng Liang ◽

Linlin Wang ◽

Chuanhua Cao ◽

Shimao Song ◽

Feng Wu

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Expression Level ◽

Small Cell Lung ◽

Poor Survival ◽

Tcga Dataset ◽

Nsclc Patients

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.

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Long intergenic noncoding RNA LINC00173 as a potential serum biomarker for diagnosis of non-small-cell lung cancer

Cancer Biomarkers ◽

10.3233/cbm-201616 ◽

2020 ◽

Vol 29 (4) ◽

pp. 441-451 ◽

Cited By ~ 1

Author(s):

Qian Yang ◽

Shan Kong ◽

Ming Zheng ◽

Yuelan Hong ◽

Jing Sun ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Differentially Expressed ◽

Diagnostic Biomarker ◽

Small Cell Lung ◽

Qrt Pcr ◽

Nsclc Patients ◽

Combined Detection

BACKGROUND: Long intergenic non-coding RNA (lincRNA) belongs to a special type of RNA that is unable to encode proteins but has been proved to play a role in gene regulation and differentially expressed in various malignant tumors. OBJECTIVE: In this study, we aimed to identify whether lincRNA LINC00173 was differentially expressed in non-small-cell lung cancer (NSCLC) and whether it could serve as a potential diagnostic biomarker. METHODS: The quantification real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00173 in serum and cultured cells. For large sample analysis, the lncRNA expression matrix in TCGA database were generated via R software. To evaluate the diagnostic performance of serum LINC00173, the receiver operating characteristic (ROC) curve was used. RESULTS: The qRT-PCR analysis showed that the serum LINC00173 expression level in 108 NSCLC patients was higher than that in 91 healthy donors and 55 patients with benign pulmonary disease (BPD). And the area under the curve (AUC) of serum LINC00173 was 0.809 for the diagnosis of NSCLC (95% CI: 0.750–0.868, p< 0.001), 0.670 for BPD (95% CI: 0.584–0.756, P< 0.001), and 0.730 for small-cell lung cancer (SCLC, 95% CI: 0.636–0.825, P< 0.001). Besides, we established a diagnostic model of combined detection of LINC00173, CEA and Cyfra21-1, and found that combined detection of these indicators significantly improved the diagnostic efficiency. Analysis of the Clinicopathological parameters showed that high LINC00173 expression was correlated with histological typing of tumor, tumor metastasis and serum Cyfra21-1 levels. In addition, serum LINC00173 expression decreased in patients who received chemotherapy and rebound in recurrent NSCLC patients. CONCLUSION: Serum LINC00173 may prove to be a potential non-invasive auxiliary diagnostic biomarker for NSCLC patients.

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Transcriptome Analysis of lncRNA-mRNA Interactions in the Non-Small Cell Lung Cancer

10.21203/rs.3.rs-57359/v1 ◽

2020 ◽

Author(s):

Bin Liu ◽

Jing Li ◽

JiMan Li ◽

GuangYuan Liu ◽

YongSheng Wang

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Biological Function ◽

Therapeutic Targets ◽

Small Cell ◽

Differentially Expressed ◽

Clinical Samples ◽

Small Cell Lung ◽

Normal Tissues

Abstract As a serious malignancy with high incidence and fatality, non-small cell lung cancer (NSCLC) has affected millions of people each year worldwide. However, the 5-year survival rate of NSCLC is still not satisfactory. Therefore, it is particularly imperative and necessary to explore the underlying molecular mechanisms of NSCLC to contribute to the potential therapeutic targets and strategies. Six clinical samples including three normal tissues and three cancer tissues obtained from patients diagnosed with NSCLC were sequenced through Illumina Hiseq2500 sequencer. Differentially expressed lncRNAs and mRNAs analysis were implemented using the edgeR, and the function of differentially expressed lncRNAs and mRNAs were analyzed with GO and KEGG enrichment analysis. Then, top 10 dysregulated lncRNAs and mRNAs were screened out. Finally, the co-expression, biological function and pathway networks of dysregulated lncRNA with the predicted target genes were constructed. Differentially expressed lncRNAs and mRNAs could distinguish cancerous tissues from normal tissues. The functions and KEGG pathway of differentially expressed lncRNAs and mRNAs mainly were enriched in immune response, metabolism, phagosome, cytokine receptor interaction and IL-17 signaling pathway. The co-expression network revealed that top ten dysregulated lncRNAs were interacted with IGH gene cluster. Furthermore, the biological function and pathway network also indicated that dysregulated lncRNAs were involved in immune process. The results demonstrated that the biologic function of dysregulated lncRNAs that may be involved in immune process. Our data provides a foundation of the biologic significances of lncRNAs to contribute to the therapeutic targets and strategies for NSCLC to promote the survival for patients.

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MicroRNA-137 and microRNA-29a expression in non-small cell lung cancer diagnosis and prognostic.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e17501 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e17501-e17501

Author(s):

Zhao Ming

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Real Time ◽

Cell Lung Cancer ◽

Expression Profiles ◽

Small Cell ◽

Cancer Tissue ◽

Rt Pcr ◽

Small Cell Lung ◽

Nsclc Patients

e17501 Background: Current staging methods are inadequate for predicting the outcome of treatment of non–small-cell lung cancer (NSCLC). We investigated whether microRNA expression proﬁles can predict clinical outcome of NSCLC patients. Methods: We studied frozen specimens of lung-cancer tissue from 76 randomly selected patients who underwent surgical resection of NSCLC. Using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, we chosed U6 as the internal control for real-time RT-PCR because it is invariant in clinical cancer specimens. We obtained microRNA137 and 29a expressions level in 76 NSCLC patients and evaluated diagnoisis value and the association between the level of expression and survival. Results: This microRNA137 is with diagnosis value, microRNA29a expression level signature is an independent predictor of the cancer relapse and survival of NSCLC patients. Conclusions: Our microRNA signature is closely associated with relapse-free and overall survival among patients with NSCLC.

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Identification and validation of aberrant regulation of miR-445-3p /TTK , miR-140-5p/TTK and miR-133b/CDCA8 in small-cell lung cancer via bioinformatics analysis

10.21203/rs.3.rs-25687/v1 ◽

2020 ◽

Author(s):

Ming-bo Tang ◽

Xin-liang Gao ◽

Zhuo-yuan Xin ◽

Li-nan Fang ◽

Wei Liu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Expression Profiles ◽

Small Cell ◽

Functional Enrichment ◽

Differentially Expressed ◽

Small Cell Lung ◽

Hub Genes ◽

Hub Gene

Abstract Background: Small-cell lung cancer (SCLC) remains the leading form of malignant lung cancer, but little bioinformation on SCLC is available. This study explored the molecular targets of SCLC by evaluating differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) (DEMs).Methods: Five mRNA expression profiles and two miRNAs expression profiles from Gene Expression Omnibus (GEO) were downloaded. R software was utilized to analyze the DEGs and DEMs between SCLC and normal samples. The DEGs were analyzed via functional enrichment analyses and were used to construct protein-protein interaction (PPI) networks. DEM targets were then predicted and intersected with the DEGs. Furthermore, the hub genes of SCLC in the overlapping DEGs were analyzed in Oncomine. Finally, the expression of DEM-hub gene pairs were verified in tissues by RT-qPCR and Western blotting.Results: In total, 236 common DEGs and 104 common DEMs were identified. Functional enrichment analysis showed the DEGs were primarily enriched in ‘cell cycle’, ‘DNA replication’ and ‘oocyte meiosis’. Twenty hub genes and five modules were identified from the PPI network. Furthermore, 6732 targeted genes of the DEMs were predicted. After intersecting with DEGs, 54 genes and 153 miRNA-mRNA pairs were eventually identified aberrant regulation in SCLC. MiR-445-3p/TTK, miR-140-5p/TTK and miR-133b/CDCA8 were identified as DEM-hub gene pairs. Oncomine analysis confirmed the overexpression of TTK and CDCA8 in SCLC. Further validation demonstrated that TTK and CDCA8 levels in SCLC tissue samples were markedly increased relative to normal controls, while miR-445-3p, miR-140-5p, and miR-133b levels were lower in SCLC samples than in controls.Conclusions: Our results revealed key miRNA-mRNA pairs associated with SCLC, providing new insights into potential disease targets.

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Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-1329 ◽

2020 ◽

Vol 58 (9) ◽

pp. 1535-1545 ◽

Cited By ~ 3

Author(s):

Ning Wang ◽

Wei Guo ◽

Xingguo Song ◽

Lisheng Liu ◽

Limin Niu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Expression Profiles ◽

Small Cell ◽

Potential Candidate ◽

Small Cell Lung ◽

Diagnostic Biomarkers ◽

Metastatic Nsclc ◽

Nsclc Patients

AbstractBackgroundExosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC).MethodsIn this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLC patients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort.ResultsNSCLC patients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLC patients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLC patients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC.ConclusionsThis novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC.

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