miR-224, miR-147b and miR-31 associated with lymph node metastasis and prognosis for lung adenocarcinoma by regulating PRPF4B, WDR82 or NR3C2

Background The present study is to screen lymph node metastasis-related microRNAs (miRNAs) in lung adenocarcinoma (LUAD) and uncover their underlying mechanisms. Methods The miRNA microarray dataset was collected from the Gene Expression Omnibus database under accession number GSE64859. The differentially expressed miRNAs (DEMs) were identified using a t-test. Target genes of DEMs were predicted through the miRWalk2.0 database. The function of these target genes was annotated with the clusterProfiler and the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools. Protein-protein interaction network was established using the STRING database to extract hub target genes. The expressions and associations with survival and lymph node metastasis of miRNAs and target genes were validated by analysis of The Cancer Genome Atlas (TCGA) dataset. Results Eight DEMs were identified between lymph node metastasis and non-metastasis samples of GSE64859 dataset. miRNA-target gene pairs were predicted between six DEMs and 251 target genes (i.e. hsa-miR-224-PRPF4B, hsa-miR-147b-WDR82 and hsa-miR-31-NR3C2). The clusterProfiler analysis showed WDR82 was involved in the mRNA surveillance pathway, while the GO enrichment analysis using the DAVID database indicated PRPF4B participated in the protein phosphorylation and NR3C2 was related with the transcription, DNA-templated. WDR82 and PRPF4B may be hub genes because they could interact with others. Two DEMs (miR-31-5p and miR-31-3p) and 45 target genes (including PRPF4B and NR3C2) were significantly associated with overall survival. The expressions of miR-224 and miR-147b were validated to be upregulated, while WDR82, PRPF4B and NR3C2 were downregulated in lymph node metastasis samples of TCGA datasets compared with non-metastasis samples. Also, there were significantly negative expression correlations between miR-147b and WDR82, between miR-224 and PRPF4B, as well as between miR-31 and NR3C2 in LUAD samples. Conclusions The present study identified several crucial miRNA-mRNA interaction pairs, which may provide novel explanations for the lymph node metastasis and poor prognosis for LUAD patients.

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Identification of lymph node metastasis-related microRNAs in lung adenocarcinoma and analysis of the underlying mechanisms using a bioinformatics approach

Experimental Biology and Medicine ◽

10.1177/1535370216677353 ◽

2016 ◽

Vol 242 (7) ◽

pp. 709-717 ◽

Cited By ~ 16

Author(s):

Li Yan ◽

Demin Jiao ◽

Huizhen Hu ◽

Jian Wang ◽

Xiali Tang ◽

...

Keyword(s):

Transcription Factors ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Lung Adenocarcinoma ◽

Lymphatic Metastasis ◽

Target Genes ◽

Bioinformatics Analyses ◽

Node Metastasis ◽

Primary Lung Adenocarcinoma ◽

Underlying Mechanisms

This study aimed to screen lymphatic metastasis-related microRNAs (miRNAs) in lung adenocarcinoma and explore their underlying mechanisms using bioinformatics. The miRNA expression in primary lung adenocarcinoma, matched adjacent non-tumorigenic and lymph node metastasis tissues of patients were profiled via microarray. The screened metastasis-related miRNAs were then validated using quantitative real-time PCR in a second cohort of lung adenocarcinoma patients with lymphatic metastasis. Significance was determined using a paired t-test. Target genes of the metastasis-related miRNAs were predicted using TargetScan, and transcription factors (TFs) were predicted based on the TRANSFAC and ENCODE databases. Furthermore, the related long non-coding RNAs (lncRNAs) were screened with starBase v2.0. The miRNA-TF-mRNA and lncRNA-miRNA-mRNA networks were constructed to determine the key interactions associated with lung adenocarcinoma metastasis. According to the miRNA microarray results, there were 10 miRNAs that were differentially expressed in metastatic tissues compared with primary tumor and adjacent non-tumorigenic tissues. Among them were increased levels of miR-146a-5p, miR-342-3p, and miR-150-5p, which were validated in the second cohort. Based on the miRNA-TF-mRNA network, vascular endothelial growth factor A and transcription factors (TFs) including TP53, SMAD4, and EP300 were recognized as critical targets of the three miRNAs. Interactions involving SNHG16–miR-146a-5p–SMAD4 and RP6-24A23.7–miR-342-3p/miR-150-5p–EP300 were highlighted according to the lncRNA-miRNA-mRNA network. miR-146a-5p, miR-342-3p, and miR-150-5p are lymphatic metastasis-related miRNAs in lung adenocarcinoma. Bioinformatics analyses demonstrated that SNHG16 might inhibit the interaction between miR-146a-5p and SMAD4, while RP6-24A23.7 might weaken miR-342-3p–EP300 and miR-150-5p–EP300 interactions in metastasis.

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Identification of genes associated with lymph node metastasis in papillary thyroid carcinoma by weighted gene co-expression network analysis

10.21203/rs.2.23820/v1 ◽

2020 ◽

Author(s):

Zhen Liu ◽

Mingyue Guo ◽

Lidong Wang ◽

Chenxi Liu ◽

Yonglian Huang

Keyword(s):

Lymph Node ◽

Network Analysis ◽

Lymph Node Metastasis ◽

Biological Significance ◽

Interaction Network ◽

Enrichment Analysis ◽

Data Set ◽

Node Metastasis ◽

Gene Modules ◽

Differential Genes

Abstract Background: Thyroid cancer (TC) is the most common endocrine malignant tumor, in which thyroid papillary carcinoma has the highest incidence of (PTC). However, some patients will relapse or even die because of tumor metastasis. Therefore, for the treatment of PTC, it is extremely important to find gene targets and their potential biomarkers. We obtained the RNA sequence matrix of PTC and the clinical information of the corresponding samples in the TCGA database. Methods: The weighted gene co-expression network analysis was utilized to construct the co-expression network, and the gene modules with high correlation among genes and the relationship between genes and clinical traits were established. Results: We utilized the screened 5271 genes for WGCNA analysis and constructed 19 gene modules. Genes in the magenta module with the highest correlation with lymph node metastasis were selected for enrichment analysis to construct a protein interaction network. After that, we selected 12 hub genes of this module by using the intersection of the differential genes in the data set of cytoscape and GEO database. 12 genes were visualized in GEPIA. After that, the gene expression was verified on the oncomine page, and 8 genes with high correlation with TC lymph metastasis (ARNTL, CDH3, CLDN1, COL8A1, COL8A2, IL1RAP, LPAR5) were screened. Conclusion: In this paper, the differential genes are screened by combining the datasets of TCGA, GEO and Oncomine in TC for the first time, which makes the screened differential genes have more biological significance. These genes may offer new insights for the treatment of PTC lymph node metastasis.

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Identification of Mirna Signature and Key Genes in Colorectal Cancer Lymph Node Metastasis

10.21203/rs.3.rs-385507/v1 ◽

2021 ◽

Author(s):

Xi Wang ◽

Guangyu Gao ◽

Zhengrong Chen ◽

Zhihao Chen ◽

Mingxiao Han ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Bioinformatic Analysis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Cancer Statistics ◽

Node Metastasis ◽

Novel Mirna

Abstract Background: miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis and therapy of colorectal cancer (CRC), whose metastasis to lymph node is closely related to the poor prognosis. The current study aimed to identify the novel gene signatures in the lymph node metastasis of CRC.Methods: GSE56350, GSE70574 and GSE95109 were downloaded from the Gene Expression Omnibus (GEO) database and 569 colorectal cancer statistics were also downloaded from the The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DE-miRNAs) were calculated by using R software. Besides, gene ontology and Enriched pathway analysis of target mRNAs were analyzed by using FunRich. Furthermore, the mRNA-miRNA network was constructed using Cytoscape software. Gene expression level was verified by GEO datasets and forty paired lymph node non-metastasis CRC tissues and lymph node metastatic CRC tissues obtained from patients with CRC using quantitative real-time PCR (qPCR) .Results: In total, five DE-miRNAs were selected, and 34 mRNAs were identified after filtering. Moreover, 2 key miRNAs and one gene were identified including hsa-miR-99a, has-miR-100 and heparan sulfate-glucosamine 3-sulfotransferase 2 (HS3ST2). The GEO datasets analysis and qPCR results showed the expression of key miRNA and genes were consistent with that in the bioinformatic analysis. A novel miRNA-mRNA network, hsa-miR-99a-HS3ST2-has-miR-100 was found in lymph node metastasis of CRC after expression analysis, prognostic prediction and experiments confirmation.Conclusions: In summary, the potential miRNAs and genes were found and a novel miRNA-mRNA network was established in CRC lymph node metastasis by systematic bioinformatic analysis and experiments validation, which may be used as potential biomarkers in the development of lymph node metastatic CRC.

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Expression of Vascular Endothelial Growth Factors C and D Correlates with Lymphangiogenesis and Lymph Node Metastasis in Lung Adenocarcinoma

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0029-1185625 ◽

2009 ◽

Vol 57 (05) ◽

pp. 291-294 ◽

Cited By ~ 13

Author(s):

Cong Bo ◽

Dong Xiaopeng ◽

Peng Chuanliang ◽

Zhao Xiaogang

Keyword(s):

Lymph Node ◽

Growth Factors ◽

Lymph Node Metastasis ◽

Lung Adenocarcinoma ◽

Vascular Endothelial Growth Factors ◽

Vascular Endothelial ◽

Node Metastasis ◽

Endothelial Growth Factors

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A Clinicopathological Study of Small Lung Adenocarcinoma 1 cm or Less in Size: Emphasis on Histological Subtypes Associated With Lymph Node Metastasis and Recurrence

International Journal of Surgical Pathology ◽

10.1177/1066896917721649 ◽

2017 ◽

Vol 26 (1) ◽

pp. 4-11 ◽

Cited By ~ 6

Author(s):

Wei Zhao ◽

Hui Wang ◽

Jun Xie ◽

Bo Tian

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Lung Adenocarcinoma ◽

Who Classification ◽

Limited Resection ◽

Adenocarcinoma In Situ ◽

Invasive Adenocarcinoma ◽

Node Metastasis ◽

Minimally Invasive Adenocarcinoma

Background. The aim of this study was to assess the prognostic significance of the newly proposed 2015 World Health Organization (WHO) lung adenocarcinoma classification for patients undergoing resection for small (≤1 cm) lung adenocarcinoma. We also investigated whether lobectomy offers prognostic advantage over limited resection for this category of tumors. Methods. A retrospective study of resected pulmonary adenocarcinomas (n = 83) in sizes 1 cm or less was carried out in which comprehensive histologic subtyping was assessed according to the 2015 WHO classification on all consecutive patients who underwent lobectomy or limited resection between 1998 and 2012. Correlation between clinicopathologic parameters and the difference in recurrence between lobectomy and limited resection group was evaluated. Results. Our data show that the proposed 2015 WHO classification identifies histological subsets of small lung adenocarcinomas with significant differences in prognosis. No recurrence was noted for patients with adenocarcinoma in situ and minimally invasive adenocarcinoma. Invasive adenocarcinomas displayed high heterogeneity and the presence of micropapillary component of 5% or greater in adenocarcinomas was significantly related to lymph node involvement and recurrence ( P < .001). Stage IA patients who underwent limited resection had a higher risk of recurrence than did those treated by lobectomy ( P < .05). Conclusions. Application of the 2015 WHO classification identifies patients with adenocarcinoma in situ and minimally invasive adenocarcinoma had excellent prognosis. Micropapillary pattern was associated with high risk of lymph node metastasis and recurrence.

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Identification of Key miRNAs in the Treatment of Dabrafenib-Resistant Melanoma

BioMed Research International ◽

10.1155/2021/5524486 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Guangyu Gao ◽

Zhen Yao ◽

Jiaofeng Shen ◽

Yulong Liu

Keyword(s):

Drug Resistance ◽

Molecular Mechanism ◽

Target Genes ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Protein Protein Interaction ◽

Obvious Association

Dabrafenib resistance is a significant problem in melanoma, and its underlying molecular mechanism is still unclear. The purpose of this study is to research the molecular mechanism of drug resistance of dabrafenib and to explore the key genes and pathways that mediate drug resistance in melanoma. GSE117666 was downloaded from the Gene Expression Omnibus (GEO) database and 492 melanoma statistics were also downloaded from The Cancer Genome Atlas (TCGA) database. Besides, differentially expressed miRNAs (DEMs) were identified by taking advantage of the R software and GEO2R. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and FunRich was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to identify potential pathways and functional annotations linked with melanoma chemoresistance. 9 DEMs and 872 mRNAs were selected after filtering. Then, target genes were uploaded to Metascape to construct protein-protein interaction (PPI) network. Also, 6 hub mRNAs were screened after performing the PPI network. Furthermore, a total of 4 out of 9 miRNAs had an obvious association with the survival rate ( P < 0.05 ) and showed a good power of risk prediction model of over survival. The present research may provide a deeper understanding of regulatory genes of dabrafenib resistance in melanoma.

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Comparison between solid component size on thin-section CT and pathologic lymph node metastasis and local invasion in T1 lung adenocarcinoma

Japanese Journal of Radiology ◽

10.1007/s11604-017-0610-6 ◽

2017 ◽

Vol 35 (3) ◽

pp. 109-115 ◽

Cited By ~ 5

Author(s):

Hideyuki Hayashi ◽

Kazuto Ashizawa ◽

Yukihiro Ogihara ◽

Akifumi Nishida ◽

Keitaro Matsumoto ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Lung Adenocarcinoma ◽

Thin Section ◽

Solid Component ◽

Component Size ◽

Local Invasion ◽

Node Metastasis ◽

Pathologic Lymph Node

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ASAP1 promotes tumor progression and angiogenesis and independently predicts poor prognosis and lymph node metastasis of gastric cancer

10.21203/rs.2.17932/v1 ◽

2019 ◽

Author(s):

Hongyu Gao ◽

Ling Qin ◽

Huawen Shi ◽

Hongfeng Zhang ◽

Chunfeng Li ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Tumor Growth ◽

Tumor Progression ◽

Epithelial Mesenchymal Transition ◽

The Cancer Genome Atlas ◽

Mesenchymal Transition ◽

Node Metastasis ◽

Tumor Cell Motility

Abstract Background: Although ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1(ASAP1) is involved in the development of various malignancies, its clinical significance and mechanism in gastric cancer (GC) remains unclear.Methods: The effects of ASAP1 on tumor progression, angiogenesis, and epithelial-mesenchymal transition were evaluated in vitro. The effects of ASAP1 on tumor growth and angiogenesis were also explored in vivo. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to gather ASAP1 expression data.Results: It showed that ASAP1 expression strongly correlated with the TNM stage (P < 0.0001) and lymph node metastasis (P < 0.0001). Multivariate analyses indicated that ASAP1 overexpression (P < 0.0001) was an independent predictor for overall survival in patients with GC. Moreover, the results revealed that ASAP1 overexpression was independently related to lymph node metastasis (P = 0.0001). ASAP1 knockdown inhibited tumor cell motility, migration, invasion, and angiogenesis, which was accompanied with the downregulation of metastatic and angiogenic biomarkers. Furthermore, ASAP1 inhibition resulted in the simultaneous downregulation of mesenchymal markers and upregulation of epithelial markers. In addition, ASAP1 promoted tumor growth and angiogenesis in the xenograft mice model. The combined datasets (TCGA and GEO) suggested that ASAP1 was associated with malignant behavior of tumor and tumor invasion, metastasis, and angiogenesis.Conclusion: To our knowledge, our study is the first to reveal that ASAP1 promotes tumor progression and angiogenesis, and indicates a prognostic potential in GCs.

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