scholarly journals TBX5-AS1, an enhancer RNA, is a potential novel prognostic biomarker for lung adenocarcinoma

2021 ◽  
Author(s):  
Lin Cheng ◽  
Tong Han ◽  
Bolin Chen ◽  
Kechao Nie ◽  
Weijun Peng
Keyword(s):  
Correlation Analysis ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Target Genes ◽  
Prognostic Biomarker ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Pcr Analysis ◽  
Qrt Pcr ◽  
Pan Cancer

Abstract Background: Enhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. However, the role of eRNAs in lung adenocarcinoma (LUAD) remains largely unclear. Thus, a comprehensive analysis was constructed to identify the key eRNAs, and to explore the clinical utility of the identified eRNAs in LUAD.Methods: First, LUAD expression profile data from the Cancer Genome Atlas (TCGA) dataset and eRNA-relevant information were integrated for Kaplan-Meier survival analysis and Spearman’s correlation analysis to filtered the key candidate eRNAs that was associated with survival rate and their target genes in LUAD. Then, the key eRNA was selected for subsequent clinical correlation analysis. KEGG pathway enrichment analyses were undertaken to explore the potential signaling pathways of the key eRNA. Data from the human protein atlas (HPA) database were used to validate the outcomes and the quantitative real time-polymerase chain reaction (qRT-PCR) analysis was conducted to measure eRNA expression levels in tumour tissues and paired normal adjacent tissues from LUAD patients. Finally, the eRNAs were validated in pan-cancer.Results: As a result, TBX5-AS1 was identified as the key eRNA, which has T-box transcription factor 5 (TBX5) as its regulatory target. KEGG analysis indicated that TBX5-AS1 may exert a vital role via the PI3K/AKT pathway. Additionally, the qRT-PCR results and the HPA database indicated that TBX5-AS1 and TBX5 were significantly downregulated in tumour samples compared to matched-adjacent pairs. The pan-cancer validation results showed that TBX5-AS1 was associated with survival in four tumours, namely, adrenocortical carcinoma (ACC), LUAD, lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). Correlations were found between TBX5-AS1 and its target gene, TBX5, in 26 tumour types.Conclusion: Collectively, we supposed that TBX5-AS1 is a tumor suppressor, and could be a new prognostic biomarker for LUAD patients and promote the targeted therapy of LUAD.

scholarly journals TBX5-AS1, an enhancer RNA, is a potential novel prognostic biomarker for lung adenocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Cheng ◽  
Tong Han ◽  
Bolin Chen ◽  
Kechao Nie ◽  
Weijun Peng
Keyword(s):  
Correlation Analysis ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Prognostic Biomarker ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Pcr Analysis ◽  
Ras Signaling ◽  
Qrt Pcr ◽  
Pan Cancer

Abstract Background Enhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. However, the role of eRNAs in lung adenocarcinoma (LUAD) remains largely unclear. Thus, a comprehensive analysis was constructed to identify the key eRNAs, and to explore the clinical utility of the identified eRNAs in LUAD. Methods First, LUAD expression profile data from the Cancer Genome Atlas (TCGA) dataset and eRNA-relevant information were integrated for Kaplan-Meier survival analysis and Spearman’s correlation analysis to filtered the key candidate eRNAs that was associated with survival rate and their target genes in LUAD. Then, the key eRNA was selected for subsequent clinical correlation analysis. KEGG pathway enrichment analyses were undertaken to explore the potential signaling pathways of the key eRNA. Data from the human protein atlas (HPA) database were used to validate the outcomes and the quantitative real time-polymerase chain reaction (qRT-PCR) analysis was conducted to measure eRNA expression levels in tumor tissues and paired normal adjacent tissues from LUAD patients. Finally, the eRNAs were validated in pan-cancer. Results As a result, TBX5-AS1 was identified as the key eRNA, which has T-box transcription factor 5 (TBX5) as its regulatory target. KEGG analysis indicated that TBX5-AS1 may exert a vital role via the PI3K/AKT pathway, Ras signaling pathway, etc. Additionally, the qRT-PCR results and the HPA database indicated that TBX5-AS1 and TBX5 were significantly downregulated in tumour samples compared to matched-adjacent pairs. The pan-cancer validation results showed that TBX5-AS1 was associated with survival in four tumors, namely, adrenocortical carcinoma (ACC), LUAD, lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). Correlations were found between TBX5-AS1 and its target gene, TBX5, in 26 tumor types. Conclusion Collectively, our results indicated that TBX5-AS1 may be a potential prognostic biomarker for LUAD patients and promote the targeted therapy of LUAD.

scholarly journals FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2083
Author(s):  
Keiko Mizuno ◽  
Kengo Tanigawa ◽  
Nijiro Nohata ◽  
Shunsuke Misono ◽  
Reona Okada ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Target Genes ◽  
Ectopic Expression ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
The Cancer Genome Atlas ◽  
Aberrant Expression ◽  
Therapeutic Molecules ◽  
Cancer Tissues

Lung adenocarcinoma (LUAD) is the most aggressive cancer and the prognosis of these patients is unfavorable. We revealed that the expression levels of both strands of miR-99a (miR-99a-5p and miR-99a-3p) were significantly suppressed in several cancer tissues. Analyses of large The Cancer Genome Atlas (TCGA) datasets showed that reduced miR-99a-5p or miR-99a-3p expression is associated with worse prognoses in LUAD patients (disease-free survival (DFS): p = 0.1264 and 0.0316; overall survival (OS): p = 0.0176 and 0.0756, respectively). Ectopic expression of these miRNAs attenuated LUAD cell proliferation, suggesting their tumor-suppressive roles. Our in silico analysis revealed 23 putative target genes of pre-miR-99a in LUAD cells. Among these targets, high expressions of 19 genes were associated with worse prognoses in LUAD patients (OS: p < 0.05). Notably, FAM64A was regulated by both miR-99a-5p and miR-99a-3p in LUAD cells, and its aberrant expression was significantly associated with poor prognosis in LUAD patients (OS: p = 0.0175; DFS: p = 0.0276). FAM64A knockdown using siRNAs suggested that elevated FAM64A expression contributes to cancer progression. Aberrant FAM64A expression was detected in LUAD tissues by immunostaining. Taken together, our miRNA-based analysis might be effective for identifying prognostic and therapeutic molecules in LUAD.

scholarly journals Identification of a novel prognosis-associated ceRNA network in lung adenocarcinoma via bioinformatics analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yumiao Li ◽  
Xiaoxue Yu ◽  
Yuhao Zhang ◽  
Xiaofang Wang ◽  
Linshan Zhao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Microarray Data ◽  
Messenger Rna ◽  
Target Genes ◽  
Nonsmall Cell Lung Cancer ◽  
The Cancer Genome Atlas ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Cerna Network

Abstract Background Lung adenocarcinoma (LUAD) is the most common subtype of nonsmall-cell lung cancer (NSCLC) and has a high incidence rate and mortality. The survival of LUAD patients has increased with the development of targeted therapeutics, but the prognosis of these patients is still poor. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of LUAD. The purpose of this study was to identify novel abnormally regulated lncRNA–microRNA (miRNA)–messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks that may suggest new therapeutic targets for LUAD or relate to LUAD prognosis. Methods We used the SBC human ceRNA array V1.0 to screen for differentially expressed (DE) lncRNAs and mRNAs in four paired LUAD samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the DE lncRNAs and mRNAs. R bioinformatics packages, The Cancer Genome Atlas (TCGA) LUAD database, and Kaplan–Meier (KM) survival analysis tools were used to validate the microarray data and construct the lncRNA–miRNA–mRNA ceRNA regulatory network. Then, quantitative real-time PCR (qRT-PCR) was used to validate the DE lncRNAs in 7 LUAD cell lines. Results A total of 2819 DE lncRNAs and 2396 DE mRNAs (P < 0.05 and fold change ≥ 2 or ≤ 0.5) were identified in four paired LUAD tissue samples. In total, 255 of the DE lncRNAs were also identified in TCGA. The GO and KEGG analysis results suggested that the DE genes were most enriched in angiogenesis and cell proliferation, and were closely related to human cancers. Moreover, the differential expression of ENST00000609697, ENST00000602992, and NR_024321 was consistent with the microarray data, as determined by qRT-PCR validation in 7 LUAD cell lines; however, only ENST00000609697 was associated with the overall survival of LUAD patients (log-rank P = 0.029). Finally, through analysis of ENST00000609697 target genes, we identified the ENST00000609697–hsa-miR-6791-5p–RASL12 ceRNA network, which may play a tumor-suppressive role in LUAD. Conclusion ENST00000609697 was abnormally expressed in LUAD. Furthermore, downregulation of ENST00000609697 and its target gene RASL12 was associated with poor prognosis in LUAD. The ENST00000609697–hsa-miR-6791-5p–RASL12 axis may play a tumor-suppressive role. These results suggest new potential prognostic and therapeutic biomarkers for LUAD.

scholarly journals Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis

Toxics ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 73
Author(s):  
Vanessa M. López-Ozuna ◽  
Ishita Gupta ◽  
Ryan Liu Chen Kiow ◽  
Emad Matanes ◽  
Hadeel Kheraldine ◽  
...  
Keyword(s):  
Head And Neck ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Pcr Analysis ◽  
Water Pipe ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
The Impact

Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient’s biology and outcome. We found that WPS can induce the epithelial–mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan–Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients’ survival.

scholarly journals ARNTL2, an Immunoregulation-Related Prognostic Biomarker in Pan-Cancer and Lung Adenocarcinoma

2021 ◽  
Author(s):  
Gujie Wu ◽  
Wenmiao Wang ◽  
Zheng Yang ◽  
Qun Xue
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Cancer Drugs ◽  
Anti Cancer ◽  
Pan Cancer

Abstract Background ARNTL2 is a member of the PAS superfamily that promotes tumor progression. However, the role of ARNTL2 in lung adenocarcinoma (LUAD) remains unclear. The purpose of our study was to investigate the function of ARNTL2 in LUAD. Methods The expression, clinical features, and prognostic role of ARNTL2 in pan-cancer were evaluated using The Cancer Genome Atlas and Genotype-Tissue Expression data. GSEA and GSVA of ARNTL2 were performed using the R package “clusterProfiler.” The correlation between immune cell infiltration level and ARNTL2 expression was analyzed using two sources of immune cell infiltration data, including the TIMER2 and ImmuCellAI database. Finally,we analyzed the correlation between ARNTL2 and IC50 of 192 drugs. Results ARNTL2 was substantially overexpressed in LUAD and pan-cancer. High ARNTL2 expression predicted poor survival in patients with LUAD. We also found that ARNTL2 expression was positively associated with the infiltration levels of immunosuppressive cells, such as tumor associated macrophages, cancer associated fibroblasts and Tregs. Among the 192 anti-cancer drugs, ARNTL2 expression was positively correlated with IC50 of 114 anti-cancer drugs, such as SB505124, Doramapimod, Nutlin-3a (-), Sabutoclax, AZD5991, PF-4708671, Elephantin, PRIMA-1MET, Sorafenib, Vorinostat, and MK-2206. Conclusions Our results revealed that ARNTL2 is a potential prognostic biomarker in LUAD. An elevated ARNTL2 expression indicates an immunosuppressive microenvironment, and targeted therapies against ARNTL2 have excellent potential.

scholarly journals Comprehensive analysis of competitive endogenous RNA associated with immune infiltration in lung adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjie Chen ◽  
Wen Li ◽  
Zhenkun Liu ◽  
Guangzhi Ma ◽  
Yunfu Deng ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Mast Cells ◽  
Correlation Analysis ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Cerna Network ◽  
Monocytes And Macrophages ◽  
Competitive Endogenous Rna

AbstractTo identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan–Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, and has-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that the FKBP3 was associated with Monocytes and Macrophages M1, and the GPI was obviously related with Monocytes and Macrophages M1. Besides, the LOXL2 was associated with Monocytes and Activated mast cells, and the IL22RA1 was significantly associated with Monocytes and Macrophages M1, while the GPR37 and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.

scholarly journals UBE2D1 RNA Expression Was an Independent Unfavorable Prognostic Indicator in Lung Adenocarcinoma, but Not in Lung Squamous Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Data ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Rna Expression

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.

scholarly journals DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianlin Chen ◽  
Junping Ding ◽  
Wenjie Huang ◽  
Lin Sun ◽  
Jinping Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Function Analysis ◽  
Mrna Level ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Diagnostic Efficiency ◽  
Protein Levels ◽  
Normal Tissues

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680, p = 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.

scholarly journals Increased GOLM1 Expression Independently Predicts Unfavorable Overall Survival and Recurrence-Free Survival in Lung Adenocarcinoma

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481877800 ◽  
Author(s):  
Xi Liu ◽  
Lei Chen ◽  
Tao Zhang
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Methylation Status ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Recurrence Free Survival ◽  
Free Survival

Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.

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