Integrated Dissection of lncRNA-miRNA-mRNA Pairs and Potential Regulatory Role of lncRNA PCAT19 in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is the main cause of cancer-related deaths worldwide. Long noncoding RNAs have been reported to play an important role in various cancers due to their special functions. Therefore, identifying the lncRNAs involved in LUAD tumorigenesis and development can help improve therapeutic strategies. The TCGA-LUAD RNA expression profile was downloaded from The Cancer Genome Atlas, and a total of 49 differential lncRNAs, 112 differential miRNAs, and 2,953 differential mRNAs were screened. Through Kaplan–Meier curves, interaction networks, hub RNAs (lncRNAs, miRNAs, and mRNAs) were obtained. These hub genes are mainly involved in cell proliferation, cell cycle, lung development, and tumor-related signaling pathways. Two lncRNAs (SMIM25 and PCAT19) more significantly related to the prognosis of LUAD were screened by univariate Cox analysis, multivariate Cox analysis, and risk model analysis. The qPCR results showed that the expression levels of SMIM25 and PCAT19 were downregulated in clinical tissues, A549 and SPC-A1 cells, which were consistent with the bioinformatics analysis results. Subsequently, the PCAT19/miR-143-3p pairs were screened through the weighted gene co-expression network analysis and miRNA-lncRNA regulatory network. Dual luciferase detection confirmed that miR-143-3p directly targets PCAT19, and qPCR results indicated that the expression of the two is positively correlated. Cell function tests showed that overexpression of PCAT19 could significantly inhibit the proliferation, migration, and invasion of A549 and SPC-A1 cells. In contrast, knockout of PCAT19 can better promote the proliferation and migration of A549 and SPC-A1 cells. The expression of PCAT19 was negatively correlated with tumor grade, histological grade, and tumor mutation load in LUAD. In addition, co-transfection experiments confirmed that the miR-143-3p mimic could partially reverse the effect of PCAT19 knockout on the proliferation of A549 and SPC-A1 cells. In summary, PCAT19 is an independent prognostic factor in patients with LUAD that can regulate the proliferation, migration, and invasion of LUAD cells and may be a potential biomarker for the diagnosis of LUAD. PCAT19/miR-143-3p plays a very important regulatory role in the occurrence and development of LUAD.

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FADS1 is a Prognostic Biomarker in Bladder Cancer: A Study Based on TCGA Data

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200925104911 ◽

2020 ◽

Vol 23 ◽

Author(s):

Ying Lu ◽

Jing Shao ◽

Xu Shu ◽

Yaofei Jiang ◽

Jianfang Rong ◽

...

Keyword(s):

Bladder Cancer ◽

Histological Grade ◽

Clinical Stage ◽

Fatty Acid Desaturase ◽

Clinical Information ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Normal Tissues ◽

Potential Biomarker ◽

T Classification

Aim and Objective: Fatty acid desaturase 1 (FADS1) has been reported to be a potential biomarker in various cancers. However, no study has explored the relationship between FADS1 expression and bladder cancer. Our study aimed to investigate the role of FADS1 in bladder cancer prognosis via The Cancer Genome Atlas (TCGA). Materials and Methods: RNA-Seq expression of 414 tumor tissues and 19 paired normal tissues, as well as corresponding clinical data, were downloaded from TCGA database. Two cancer cases were excluded due to a lack of clinical information. The association between FADS1 and the clinicopathological features of bladder cancer was analyzed. This study was conducted in October of 2019 in China. Results: The high expression of FADS1 in bladder cancer was significantly related to histological grade (OR = 0.155 for low vs. high), clinical stage (OR=2.074 for III or IV vs. I or II), T classification (OR=2.326 for T3 or T4 vs. T1 or T2), lymphatic metastasis (OR=1.923 for N1 or N2 or N3 vs. N0) and distant metastasis (OR=4.883 for yes vs. no) (all p-values <0.05). Bladder cancer with high FADS1 levels was related to a worse prognosis than bladder cancer with low FADS1 levels (p= 1.626*10-5 ), according to median expression value 3.622. FADS1 was an independent factor of overall survival in bladder cancer, with a hazard ratio of 1.048 (95%CI: 1.020–1.077, p = 0.001). Conclusions: Increased FADS1 expression in bladder cancer is associated with advanced clinical pathological features and may be a potential biomarker for poor prognosis.

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Deciphering N6-Methyladenosine-Related Genes Signature to Predict Survival in Lung Adenocarcinoma

BioMed Research International ◽

10.1155/2020/2514230 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Jie Zhu ◽

Min Wang ◽

Daixing Hu

Keyword(s):

Lung Adenocarcinoma ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Consensus Clustering ◽

Lasso Regression ◽

Gene Expressions ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Selection Operator ◽

Cox Analysis

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death. Among these, lung adenocarcinoma (LUAD) accounts for most cases. Due to the improvement of precision medicine based on molecular characterization, the treatment of LUAD underwent significant changes. With these changes, the prognosis of LUAD becomes diverse. N6-methyladenosine (m6A) is the most predominant modification in mRNAs, which has been a research hotspot in the field of oncology. Nevertheless, little has been studied to reveal the correlations between the m6A-related genes and prognosis in LUAD. Thus, we conducted a comprehensive analysis of m6A-related gene expressions in LUAD patients based on The Cancer Genome Atlas (TCGA) database by revealing their relationship with prognosis. Different expressions of the m6A-related genes in tumor tissues and non-tumor tissues were confirmed. Furthermore, their relationship with prognosis was studied via Consensus Clustering Analysis, Principal Components Analysis (PCA), and Least Absolute Shrinkage and Selection Operator (LASSO) Regression. Based on the above analyses, a m6A-based signature to predict the overall survival (OS) in LUAD was successfully established. Among the 479 cases, we found that most of the m6A-related genes were differentially expressed between tumor and non-tumor tissues. Six genes, HNRNPC, METTL3, YTHDC2, KIAA1429, ALKBH5, and YTHDF1 were screened to build a risk scoring signature, which is strongly related to the clinical features pathological stages (p<0.05), M stages (p<0.05), T stages (p < 0.05), gender (p=0.04), and survival outcome (p=0.02). Multivariate Cox analysis indicated that risk value could be used as an independent prognostic factor, revealing that the m6A-related genes signature has great predictive value. Its efficacy was also validated by data from the Gene Expression Omnibus (GEO) database.

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Systematic Analyses of a Chemokine Family-Based Risk Model Predicting Clinical Outcome and Immunotherapy Response in Lung Adenocarcinoma

Cell Transplantation ◽

10.1177/09636897211055046 ◽

2021 ◽

Vol 30 ◽

pp. 096368972110550

Author(s):

Jiarui Chen ◽

Xingyu Liu ◽

Qiuji Wu ◽

Xueping Jiang ◽

Zihang Zeng ◽

...

Keyword(s):

Overall Survival ◽

Lung Adenocarcinoma ◽

Risk Model ◽

Cox Regression ◽

Expression Patterns ◽

Low Risk ◽

The Cancer Genome Atlas ◽

Cox Regression Analysis ◽

Family Based ◽

Chemokine Family

Chemokines exhibited complicated functions in antitumor immunity, with their expression profile and clinical importance of lung adenocarcinoma (LUAD) patients remaining largely undetermined. This study aimed to explore the expression patterns of chemokine family in LUAD and construct a predictive chemokine family-based signature. A total of 497 samples were downloaded from the Cancer Genome Atlas (TCGA) data portal as the training set, and the combination of 4 representative Gene Expression Omnibus (GEO) datasets, including GSE30219, GSE50081, GSE37745, and GSE31210, were utilized as the validation set. A three gene-based signature was constructed using univariate and stepwise multivariate Cox regression analysis, classifying patients into high and low risk groups according to the overall survival. The independent GEO datasets were utilized to validate this signature. Another multivariate analysis revealed that this signature remained an independent prognostic factor in LUAD patients. Furthermore, patients in the low risk group featured immunoactive tumor microenvironment (TME), higher IPS scores and lower TIDE scores, and was regarded as the potential beneficiaries of immunotherapy. Finally, the role of risky CCL20 was validated by immunohistochemistry (IHC), and patients possessed higher CCL20 expression presented shorter overall survival ( P = 0.011).

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LBX2-AS1 Activates FSTL3 by Binding to Transcription Factor RARα to Foster Proliferation, Migration, and Invasion of Thyroid Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.765033 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jia Li ◽

Jie Shen ◽

Lan Qin ◽

Dongyan Lu ◽

Enci Ding

Keyword(s):

Thyroid Cancer ◽

Cancer Progression ◽

Cell Function ◽

Differential Expression Analysis ◽

Endocrine Tumor ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Cancer Tissue ◽

Data Set ◽

Rna Immunoprecipitation

Background: Thyroid cancer is a frequent endocrine tumor in women. It is of great significance to investigate the molecular mechanism of progression of thyroid cancer.Methods: Gene expression data set and clinical data were downloaded from The Cancer Genome Atlas database for differential expression analysis. The triplet of downstream transcription factors (TFs) and modulatory genes of target lncRNA in thyroid cancer was predicted by the lncMAP database. mRNA and protein expression of lncRNA LBX2-AS1, RARα, and FSTL3 were detected by qRT-PCR and western blot. The localization of lncRNA LBX2-AS1 in cells was tested by Fluorescence in situ hybridization assay. The RNA immunoprecipitation assay was applied to verify the binding relationship between lncRNA LBX2-AS1 and FSTL3. ChIP and dual-luciferase assays were used to prove the binding relationship between RARα and FSTL3. Cell function experiments were used to test cell proliferation, migration and invasion in each treatment group. The role of lncRNA LBX2-AS1 in thyroid cancer progression was also confirmed in nude mice.Results: Bioinformatics analysis indicated that lncRNA LBX2-AS1, RARα, FSTL3 were remarkably fostered in thyroid cancer tissue, and LBX2-AS1 was evidently correlated with clinical features. The LncMAP triplet prediction showed that LBX2-AS1 recruited TF RARα to modulate FSTL3. RIP assay confirmed that LBX2-AS1 was prominently enriched on RARα. ChIP and dual-luciferase report assays unveiled that RARα bound to the promoter region of FSTL3 and functioned as a TF. Cell function experiments uncovered that LBX2-AS1 boosted the progression of thyroid cancer. The rescue experiments showed that LBX2-AS1 recruited the TF RARα to hasten the transcription activity of FSTL3 and thus promoted the development of thyroid cancer.Conclusion: The integrative results demonstrated that LBX2-AS1 activated FSTL3 by binding to TF RARα to hasten proliferation, migration and invasion of thyroid cancer.

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ADAM12 as a Clinical Prognostic Indicator Associated with Tumour Immune Infiltration in Lung Adenocarcinoma

10.21203/rs.3.rs-452333/v1 ◽

2021 ◽

Author(s):

Junfan Pan ◽

Zhidong Huang ◽

Yiquan Xu

Keyword(s):

Lung Adenocarcinoma ◽

Prognostic Model ◽

Immune Cell ◽

Genetic Alterations ◽

The Cancer Genome Atlas ◽

Migration And Invasion ◽

Receptor Interaction ◽

Significant Differential Expression ◽

Immune Related Genes

Abstract Background: Lung cancer is the most common cause of cancer-related death worldwide. In humans, 22 functional α-disintegrinand metalloproteinases (ADAMs) have been identified, 12 of which have proteolytic activity. The role of ADAMs in cancer has attracted increasing attention. However, the expression and significance of ADAMs in lung adenocarcinoma (LUAD) remain unclear. The current study aimed to explore the expression and prognostic value of ADAM12 in LUAD.Methods: The Cancer Genome Atlas(TCGA) database was used to analyse the expression of ADAMs in LUAD. The cBioPortal database was used to obtain and analyse ADAM12 copy number changes, and the LinkedOmics database was utilised for the analysis of ADAM12-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was then performed using TIMER. The relationship between ADAM12 and the tumour immune microenvironment(TIM) was assessed via the TISIDB database. ADAM12 and immune-related genes were used to construct a prognostic model. Knockdown of ADAM12 was performed in vitro in order to verify its biological function. The unpaired t-test was used for comparison between the two groups, ANOVA was used for analysing differences between multiple groups, and the Kaplan-Meier test was used to compare survival between groups.Results: Most ADAMs exhibited significant differential expression in LUAD. ADAM12 expression was significantly higher in LUAD tissues than in healthy tissues, and lower ADAM12 expression was associated with better survival. Genetic alterations of ADAM12 mainly included missense mutations, amplifications, and deep deletions. ADAM12 and positively correlated genes were mainly enriched in protein digestion and absorption, ECM-receptor interaction, and adhesion plaques. ADAM12 had a moderate correlation with immune cell markers EBIP1, CCNB1, EXO1, KNTC1, PRC1 and FAM198B. Prognostic model was established based on ADAM12 and immune-related genes. In vitro experiments revealed that knocking down ADAM12 inhibited cell proliferation, migration and invasion.Conclusion: ADAM12 potentially plays an important role in the occurrence of LUAD and may be utilised as an immunotherapy target and a valuable prognostic biomarker for LUAD.

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Clinical and Prognostic Implications of an Immune-Related Risk Model Based on TP53 Status in Lung Adenocarcinoma

10.21203/rs.3.rs-105337/v1 ◽

2020 ◽

Author(s):

Xuming Song ◽

Qiang Chen ◽

Jifan Wang ◽

Qixing Mao ◽

Wenjie Xia ◽

...

Keyword(s):

T Cells ◽

Lung Adenocarcinoma ◽

Tp53 Mutation ◽

Risk Model ◽

Predictive Ability ◽

Related Model ◽

Related Risk ◽

Cox Analysis ◽

Checkpoint Genes ◽

Tp53 Status

Abstract Background: TP53 mutation is the most widespread mutation in lung adenocarcinoma (LUAD), meanwhile p53 (encoded by TP53) has recently been implicated in immune responses. However, it is still unknown whether TP53 mutation may remodel tumor microenvironment to influence tumor progression and prognosis in LUAD.Methods: we developed a six-gene immune-related model (IRM) to predict the survival of patients with LUAD in TCGA cohort based on TP53 status using LASSO Cox analysis, which was also confirmed the predictive ability in two independent cohorts.Results: The mutation of TP53 led to a decrease in the immune response in LUAD. Further analysis revealed that patients in the high-index group had observably lower relative infiltration of memory B cells and regulatory T cells, together with significantly higher relative infiltration proportions neutrophils and resting memory CD4+ T cells. Additionally, the IRM index positively correlated with expression of critical immune checkpoint genes including PDCD1 (encoding PD-1) and CD274 (encoding PD-L1), which was validated in Nanjing cohort. Furthermore, the IRM index as an independent prognostic factor was used to establish a nomogram for clinical application.Conclusion: This immune-related model may serve as a powerful prognostic tool to further optimize immunotherapies for LUAD.

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NRAS Expression is Associated With Prognosis and Tumor Immune Microenvironment in Lung Adenocarcinoma

10.21203/rs.3.rs-862652/v1 ◽

2021 ◽

Author(s):

Yueren Yan ◽

Zhendong Gao ◽

Han Han ◽

Yue Zhao ◽

Yang Zhang ◽

...

Keyword(s):

T Cells ◽

Lung Adenocarcinoma ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Immune Microenvironment ◽

Kaplan Meier ◽

Tumor Immune Microenvironment ◽

Cox Analysis

Abstract Purpose: NRAS plays a pivotal role in progression of various kinds of somatic malignancies; however, the correlation between NRAS and lung adenocarcinoma is less known. We aim to analyze the prognostic value of NRAS expression in lung adenocarcinoma, and explore the relationship between NRAS and tumor immune microenvironment. Methods: We obtained the transcriptome pofiles and clinical data of LUAD from The Cancer Genome Atlas database and three Genome Expression Omnibus datasets. Specimens from 325 patients with completely resected lung adenocarcinoma were collected for immunohistochemical assays of NRAS, PD-L1, PD-1 and TIM-3. Then we performed gene set enrichment analysis to investigate cancer-related and immune-related signaling pathways. TIMER algorithms were performed to evaluate tumor immune infiltrating cells and immune-related biomarkers.Results: Compared with adjacent non-tumor tissue, NRAS expression was significantly upregulated in LUAD tissue. NRAS expression was significantly correlated with more advanced stage and positive lymph nodes. Kaplan-Meier curves and Cox analysis suggested that high NRAS expression led to a poor prognosis, and could be an independent prognostic factor in LUAD patients. Besides, NRAS expression was positively correlated with CD8+ T cells, macrophages, and neutrophils, and negatively correlated with B cells and CD4+ T cells. The expression level of NRAS was positively correlated with PD-L1, PD-1, and TIM-3 both at RNA and protein level. Conclusions: To conclude, we found NRAS a novel prognostic biomarker in LUAD. Besides, the expression level of NRAS may influence the prognosis of LUAD via various kinds of cancer-related pathways and remodeling TIM.

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GAPLINC is a predictor of poor prognosis and regulates cell migration and invasion in osteosarcoma

Bioscience Reports ◽

10.1042/bsr20181171 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 1

Author(s):

Shian Liao ◽

Sijia Zhou ◽

Chao Wang

Keyword(s):

Cell Migration ◽

Cell Lines ◽

Histological Grade ◽

Migration And Invasion ◽

Clinical Samples ◽

Osteosarcoma Cell ◽

Loss Of Function ◽

Cell Migration And Invasion ◽

Potential Biomarker

Gastric adenocarcinoma predictive long intergenic non-coding (GAPLINC) is a novel long non-coding RNA (lncRNA) and has been found to function as an oncogenic lncRNA in gastric cancer, colorectal cancer, and bladder cancer. The expression status and biological function of GAPLINC in osteosarcoma are still unknown. Thus, we analyzed the association between GAPLINC expression and clinicopathological characteristics in osteosarcoma clinical samples, and conducted loss-of-function study in osteosarcoma cell lines. In our results, GAPLINC expression is elevated in osteosarcoma tissues and cell lines, and correlated with advanced Enneking stage, present distant metastasis, and poor histological grade. Survival analyses indicated that GAPLINC expression was negatively associated with overall survival, and GAPLINC high-expression was an independent risk factor in osteosarcoma patients. The in vitro studies showed knockdown of GAPLINC depressed osteosarcoma cell migration and invasion via inhibiting CD44 expression, but no effect on cell proliferation. In conclusion, GAPLINC may serve as a potential biomarker for predicting prognosis and developing therapy for osteosarcoma.

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Identification of a prognostic ferroptosis-related lncRNA signature in the tumor microenvironment of lung adenocarcinoma

Cell Death Discovery ◽

10.1038/s41420-021-00576-z ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yugang Guo ◽

Zhongyu Qu ◽

Dandan Li ◽

Fanghui Bai ◽

Juan Xing ◽

...

Keyword(s):

High Risk ◽

Lung Adenocarcinoma ◽

Proportional Hazards ◽

Risk Model ◽

Principal Component ◽

Cox Proportional Hazards ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Poor Overall Survival

AbstractFerroptosis is closely linked to various cancers, including lung adenocarcinoma (LUAD); however, the factors involved in the regulation of ferroptosis-related genes are not well established. In this study, we identified and characterized ferroptosis-related long noncoding RNAs (lncRNAs) in LUAD. In particular, a coexpression network of ferroptosis-related mRNAs and lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic ferroptosis-related lncRNA signature (FerRLSig). We obtained a prognostic risk model consisting of 10 ferroptosis-related lncRNAs: AL606489.1, AC106047.1, LINC02081, AC090559.1, AC026355.1, FAM83A-AS1, AL034397.3, AC092171.5, AC010980.2, and AC123595.1. High risk scores according to the FerRLSig were significantly associated with poor overall survival (hazard ratio (HR) = 1.412, 95% CI = 1.271–1.568; P < 0.001). Receiver operating characteristic (ROC) curves and a principal component analysis further supported the accuracy of the model. Next, a prognostic nomogram combining FerRLSig with clinical features was established and showed favorable predictive efficacy for survival risk stratification. In addition, gene set enrichment analysis (GSEA) revealed that FerRLSig is involved in many malignancy-associated immunoregulatory pathways. Based on the risk model, we found that the immune status and response to immunotherapy, chemotherapy, and targeted therapy differed significantly between the high-risk and low-risk groups. These results offer novel insights into the pathogenesis of LUAD, including the contribution of ferroptosis-related lncRNAs, and reveal a prognostic indicator with the potential to inform immunological research and treatment.

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A novel prognostic signature of immune-related lncRNA pairs in lung adenocarcinoma

Scientific Reports ◽

10.1038/s41598-021-96236-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yang Liu ◽

Qiuhong Wu ◽

Xuejiao Fan ◽

Wen Li ◽

Xiaogang Li ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Risk Model ◽

Area Under The Curve ◽

Roc Curves ◽

Clinicopathological Characteristics ◽

The Cancer Genome Atlas ◽

Prognostic Signature ◽

Specific Expression ◽

Expression Levels ◽

Cancer Genome Atlas

AbstractLung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.

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