scholarly journals Identification and Elucidation of the Protective isomiRs in Lung Cancer Patient Prognosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Fu-Mei Hsieh ◽  
Su-Ting Lai ◽  
Ming-Fong Wu ◽  
Chen-Ching Lin
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressors ◽  
Mature Mirnas ◽  
Antagonistic Effect ◽  
The Cancer Genome Atlas ◽  
Bidirectional Regulation ◽  
Protective Groups ◽  
Cancer Genome Atlas ◽  
Patient Prognosis ◽  
Late Stages

MicroRNAs (miRNAs) are approximately 20–22 nucleotides in length, which are well known to participate in the post-transcriptional modification. The mature miRNAs were observed to be varied on 5′ or 3′ that raise another term—the isoforms of mature miRNAs (isomiRs), which have been proven not the artifacts and discussed widely recently. In our research, we focused on studying the 5′ isomiRs in lung adenocarcinoma (LUAD) in The Cancer Genome Atlas (TCGA). We characterized 75 isomiRs significantly associated with better prognosis and 43 isomiRs with poor prognosis. The 75 protective isomiRs can successfully distinguish tumors from normal samples and are expressed differently between patients of early and late stages. We also found that most of the protective isomiRs tend to be with downstream shift and upregulated compared with those with upstream shift, implying that a possible selection occurs during cancer development. Among these protective isomiRs, we observed a highly positive and significant correlation, as well as in harmful isomiRs, suggesting cooperation within the group. However, between protective and harmful, there is no such a concordance but conversely more negative correlation, suggesting the possible antagonistic effect between protective and harmful isomiRs. We also identified that two isomiRs miR-181a-3p|-3 and miR-181a-3p|2, respectively, belong to the harmful and protective groups, suggesting a bidirectional regulation of their originated archetype—miR-181a-3p. Additionally, we found that the protective isomiRs of miR-21-5p, which is an oncomiR, may be evolved as the tumor suppressors through producing isomiRs to hinder metastasis. In summary, these results displayed the characteristics of the protective isomiRs and their potential for developing the treatment of lung cancer.

scholarly journals Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer

2018 ◽  
Vol 111 (7) ◽  
pp. 664-674 ◽  
Author(s):  
Rongqiang Yang ◽  
Steven W Li ◽  
Zirong Chen ◽  
Xin Zhou ◽  
Wei Ni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Transcriptome Profiling ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Growth And Survival ◽  
Cancer Genome Atlas ◽  
Lung Adenocarcinomas ◽  
Genome Atlas

Abstract Background The LKB1 tumor suppressor gene is commonly inactivated in non-small cell lung carcinomas (NSCLC), a major form of lung cancer. Targeted therapies for LKB1-inactivated lung cancer are currently unavailable. Identification of critical signaling components downstream of LKB1 inactivation has the potential to uncover rational therapeutic targets. Here we investigated the role of INSL4, a member of the insulin/IGF/relaxin superfamily, in LKB1-inactivated NSCLCs. Methods INSL4 expression was analyzed using global transcriptome profiling, quantitative reverse transcription PCR, western blotting, enzyme-linked immunosorbent assay, and RNA in situ hybridization in human NSCLC cell lines and tumor specimens. INSL4 gene expression and clinical data from The Cancer Genome Atlas lung adenocarcinomas (n = 515) were analyzed using log-rank and Fisher exact tests. INSL4 functions were studied using short hairpin RNA (shRNA) knockdown, overexpression, transcriptome profiling, cell growth, and survival assays in vitro and in vivo. All statistical tests were two-sided. Results INSL4 was identified as a novel downstream target of LKB1 deficiency and its expression was induced through aberrant CRTC-CREB activation. INSL4 was highly induced in LKB1-deficient NSCLC cells (up to 543-fold) and 9 of 41 primary tumors, although undetectable in all normal tissues except the placenta. Lung adenocarcinomas from The Cancer Genome Atlas with high and low INSL4 expression (with the top 10th percentile as cutoff) showed statistically significant differences for advanced tumor stage (P < .001), lymph node metastasis (P = .001), and tumor size (P = .01). The INSL4-high group showed worse survival than the INSL4-low group (P < .001). Sustained INSL4 expression was required for the growth and viability of LKB1-inactivated NSCLC cells in vitro and in a mouse xenograft model (n = 5 mice per group). Expression profiling revealed INSL4 as a critical regulator of cell cycle, growth, and survival. Conclusions LKB1 deficiency induces an autocrine INSL4 signaling that critically supports the growth and survival of lung cancer cells. Therefore, aberrant INSL4 signaling is a promising therapeutic target for LKB1-deficient lung cancers.

scholarly journals Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Chao-Yu Pan ◽  
Wei-Ting Kuo ◽  
Chien-Yuan Chiu ◽  
Wen-chang Lin
Keyword(s):  
Mirna Expression ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Visual Display ◽  
Mature Mirnas ◽  
Mobile App ◽  
The Cancer Genome Atlas ◽  
Rna Seq ◽  
Cancer Genome Atlas ◽  
User Friendly

MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

scholarly journals High expression levels of pyrimidine metabolic rate–limiting enzymes are adverse prognostic factors in lung adenocarcinoma: a study based on The Cancer Genome Atlas and Gene Expression Omnibus datasets

2020 ◽  
Vol 16 (3) ◽  
pp. 347-366 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Lung Cancer ◽  
Metabolic Rate ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Pyrimidine Metabolism ◽  
Expression Levels ◽  
Cancer Genome Atlas ◽  
Rate Limiting ◽  
Genome Atlas

Abstract Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.

scholarly journals ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bai-Quan Qiu ◽  
Xia-Hui Lin ◽  
Song-Qing Lai ◽  
Feng Lu ◽  
Kun Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Prognostic Effect ◽  
Cancer Genome Atlas

Abstract Background Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study. Methods Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells. Results We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes. Conclusion Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.

Multiomics analysis identifies key genes and pathways related to N6-methyladenosine RNA modification in ovarian cancer

Epigenomics ◽  
2021 ◽  
Author(s):  
Haoya Xu ◽  
Xianli Li ◽  
Shengtan Wang ◽  
Feifei Li ◽  
Jian Gao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Target Genes ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Rna Modification ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Number Variation ◽  
Cancer Genome Atlas ◽  
Patient Prognosis

Aims: To explore the pathways and target genes related to N6-methyladenosine (m6A) methylation in ovarian cancer and their effect on patient prognosis. Methods & materials: The Cancer Genome Atlas was used to screen genes related to m6A regulators in terms of gene expression, mutation and copy number variation. These genes were subjected to pathway enrichment analysis. Prognosis-related genes were screened and involved in risk signature construction. Immunohistochemistry was used for verification. Results: We obtained 1408 genes dysregulated in parallel to m6A regulators, which were mainly involved in the platelet activation pathway. The m6A-related signature was constructed based on the expression of four prognosis-related genes ( RPS6KA2, JUNB, HNF4A and P2RX1). Conclusion: This work provides new insights into the mechanism of m6A methylation in ovarian cancer.

scholarly journals The Cancer Genome Atlas Predicts the Prognosis of Lung Carcinoma Based on Genes Associated with m6A Methylation

2021 ◽  
Author(s):  
Huanqing Liu ◽  
Tingting Li ◽  
Chunsheng Dong ◽  
Jun Lyu
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Lung Carcinoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Predictive Values ◽  
Rna Methylation ◽  
Cancer Genome Atlas ◽  
M6a Rna Methylation ◽  
Genome Atlas

Abstract Lung cancer has become a predominant cause of death in relation with carcinoma worldwide. N6-methylladenosine (m6A) is a common mRNA that is internally modified, which has a pivotal role in mRNA splicing, outputting, localizing, and translating and in identifying stable features. This study evaluated the expression pattern and prognostic value of m6A-related genes in lung cancer. Expression data of lung cancer samples with related clinical information were obtained from The Cancer Genome Atlas (TCGA). Then, R software was used in combination with several corresponding software packages to identify the regulatory factors of m6A RNA methylation with differential expression. Three genes (METTL3, YTHDF1, and FTO) were overexpressed in lung cancer. METTL3 had a low survival rate (P < 0.05). Significant differences in survival rate were observed among the subgroups, which possessed differently expressed m6A levels. Two latent predicting factors (METTL3 and KIAA1429) that met the independent predictive values were selected. M6A RNA methylation modulators may be involved with the malignant progression of lung cancer, and the two selected risk characteristics of m6A RNA methylation regulators may be a potential prognostic biological marker for guiding customized therapies in patients with lung carcinoma.

Multiplex testing for driver mutations in squamous cell carcinomas of the lung.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7505-7505 ◽  
Author(s):  
Paul K. Paik ◽  
Adnan Hasanovic ◽  
Lu Wang ◽  
Natasha Rekhtman ◽  
Marc Ladanyi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell ◽  
Tumor Suppressors ◽  
The Cancer Genome Atlas ◽  
Driver Mutations ◽  
Personalized Care ◽  
Pik3ca Mutations ◽  
Pten Loss ◽  
Institutional Review ◽  
Multiplex Testing

7505 Background: While the majority of lung adenocarcinomas (ADCL) harbor an identifiable driver mutation, targeted therapies for squamous cell lung carcinomas (SQCLC) have lagged in development due to a paucity of druggable oncogenic events. Three targets, which together occur in up to 50% of SQCLC, have been recently identified (FGFR1 amplification, DDR2 mutations, PIK3CA mutations/PTEN loss). Comprehensive molecular analysis of SQCLC tumors by The Cancer Genome Atlas is ongoing, with new therapeutic targets on the horizon. Methods: We have instituted prospective, multiplex testing of SQCLC tumors (Squamous Cell Lung Cancer Mutation Analysis Program, “SQ-MAP”). Tests include FISH for FGFR1 amplification (defined as FGFR1:CEP8 ≥ 2 in >10% of cells), IHC for loss of PTEN expression, and Sequenom MassARRAY for PIK3CA mutations (and others, below). We are also incorporating targeted exon sequencing (Agilent SureSelect/Ion Torrent) of a panel of over 80 lung cancer oncogenes and tumor suppressors in preparation for future studies. All tests were performed on formalin-fixed paraffin-embedded samples and with Institutional Review Board/Biospecimen Utilization Committee approval. Results: 40 SQCLC patient specimens have been processed through SQ-MAP over 3 months. 8 samples were excluded (insufficient tissue in 4, reclassification to ADCL in 4). Data are available for 28 patients. PTEN IHC was performed on 15 samples to date. Molecular results are summarized in the table. Events were non-overlapping. Results for the ≥80 gene sequencing component will be described. Based on SQ-MAP, accrual to 2 approved clinical trials (FGFR1 inhibition; PI3K inhibition) has begun, with a third planned (DDR2 mutations). Conclusions: Actionable defects were detected in 60% (95% CI: 37-75%) of SQCLC specimens. Mutation data for ≥80 other oncogenes and tumor suppressors will be available shortly (including DDR2). SQ-MAP serves as a platform supporting both personalized care and research. [Table: see text]

scholarly journals Identification of ubiquitination-related genes in human glioma as indicators of patient prognosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250239
Author(s):  
Lei Wang ◽  
Yuelin Liu ◽  
Chengmin Xuan ◽  
Yong Liu ◽  
Hengliang Shi ◽  
...  
Keyword(s):  
Risk Model ◽  
Tissue Expression ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Multiple Tumor ◽  
Metabolism Regulation ◽  
Ubiquitin Proteasome ◽  
Cancer Genome Atlas ◽  
Patient Prognosis ◽  
Cox Analysis

Ubiquitination is a dynamic and reversible process of a specific modification of target proteins catalyzed by a series of ubiquitination enzymes. Because of the extensive range of substrates, ubiquitination plays a crucial role in the localization, metabolism, regulation, and degradation of proteins. Although the treatment of glioma has been improved, the survival rate of patients is still not satisfactory. Therefore, we explore the role of ubiquitin proteasome in glioma. Survival-related ubiquitination related genes (URGs) were obtained through analysis of the Genotype-Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA). Cox analysis was performed to construct risk model. The accuracy of risk model is verified by survival, Receiver operating characteristic (ROC) and Cox analysis. We obtained 36 differentially expressed URGs and found that 25 URGs were related to patient prognosis. We used the 25 URGs to construct a model containing 8 URGs to predict glioma patient risk by Cox analysis. ROC showed that the accuracy rate of this model is 85.3%. Cox analysis found that this model can be used as an independent prognostic factor. We also found that this model is related to molecular typing markers. Patients in the high-risk group were enriched in multiple tumor-related signaling pathways. In addition, we predicted TFs that may regulate the risk model URGs and found that the risk model is related to B cells, CD4 T cells, and neutrophils.

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