Aberrant status and clinicopathologic characteristic associations of 11 target genes in 1,321 Chinese patients with lung adenocarcinoma

Abstract Background This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). Methods The circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA–miRNA–mRNA). Finally, the functional analysis and drug–gene interaction analysis of mRNAs in the ceRNA network was performed. Results A total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA–miRNA and 674 miRNA–mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA–miRNA–mRNA network was constructed, containing 5 miRNA–circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA–mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs. Conclusion Three circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.

Download Full-text

Prognostic significance of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of stage I lung adenocarcinoma: A retrospective study based on analysis of 110 Chinese patients

Thoracic Cancer ◽

10.1111/1759-7714.12464 ◽

2017 ◽

Vol 8 (6) ◽

pp. 565-571 ◽

Cited By ~ 4

Author(s):

Xin Zhao ◽

Yi Zhang ◽

Kun Qian ◽

Lan Zhao ◽

Wei Wang ◽

...

Keyword(s):

Lung Cancer ◽

Retrospective Study ◽

Lung Adenocarcinoma ◽

International Association ◽

Prognostic Significance ◽

American Thoracic Society ◽

Stage I ◽

Chinese Patients ◽

European Respiratory Society

Download Full-text

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.

Download Full-text

Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽

10.7717/peerj.10470 ◽

2021 ◽

Vol 9 ◽

pp. e10470

Author(s):

Wanzhen Li ◽

Shiqing Liu ◽

Shihong Su ◽

Yang Chen ◽

Gengyun Sun

Keyword(s):

Lung Adenocarcinoma ◽

Signaling Pathway ◽

Prognostic Value ◽

Target Genes ◽

Predictive Accuracy ◽

Differentially Expressed ◽

Prognostic Signature ◽

Tissue Samples ◽

Gene Set ◽

Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

Download Full-text

From tobacco smoking to cancer mutational signature: a mediation analysis strategy to explore the role of epigenetic changes

BMC Cancer ◽

10.1186/s12885-020-07368-1 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Zhishan Chen ◽

Wanqing Wen ◽

Qiuyin Cai ◽

Jirong Long ◽

Ying Wang ◽

...

Keyword(s):

Dna Methylation ◽

Lung Adenocarcinoma ◽

Tobacco Smoking ◽

Mediation Analysis ◽

Target Genes ◽

Cancer Genome ◽

Gene Expressions ◽

Mutational Signature ◽

Tumor Tissues ◽

Dna Methylations

Abstract Background Tobacco smoking is associated with a unique mutational signature in the human cancer genome. It is unclear whether tobacco smoking-altered DNA methylations and gene expressions affect smoking-related mutational signature. Methods We systematically analyzed the smoking-related DNA methylation sites reported from five previous casecontrol studies in peripheral blood cells to identify possible target genes. Using the mediation analysis approach, we evaluated whether the association of tobacco smoking with mutational signature is mediated through altered DNA methylation and expression of these target genes in lung adenocarcinoma tumor tissues. Results Based on data obtained from 21,108 blood samples, we identified 374 smoking-related DNA methylation sites, annotated to 248 target genes. Using data from DNA methylations, gene expressions and smoking-related mutational signature generated from ~ 7700 tumor tissue samples across 26 cancer types from The Cancer Genome Atlas (TCGA), we found 11 of the 248 target genes whose expressions were associated with smoking-related mutational signature at a Bonferroni-correction P < 0.001. This included four for head and neck cancer, and seven for lung adenocarcinoma. In lung adenocarcinoma, our results showed that smoking increased the expression of three genes, AHRR, GPR15, and HDGF, and decreased the expression of two genes, CAPN8, and RPS6KA1, which were consequently associated with increased smoking-related mutational signature. Additional evidence showed that the elevated expression of AHRR and GPR15 were associated with smoking-altered hypomethylations at cg14817490 and cg19859270, respectively, in lung adenocarcinoma tumor tissues. Lastly, we showed that decreased expression of RPS6KA1, were associated with poor survival of lung cancer patients. Conclusions Our findings provide novel insight into the contributions of tobacco smoking to carcinogenesis through the underlying mechanisms of the elevated mutational signature by altered DNA methylations and gene expressions.

Download Full-text

Relevance of EGFR mutation with micropapillary pattern according to the novel IASLC/ATS/ERS lung adenocarcinoma classification and correlation with prognosis in Chinese patients

Lung Cancer ◽

10.1016/j.lungcan.2014.08.018 ◽

2014 ◽

Vol 86 (2) ◽

pp. 164-169 ◽

Cited By ~ 17

Author(s):

Liu Chao ◽

Huang Yi-Sheng ◽

Chen Yu ◽

Yan Li-Xu ◽

Luo Xin-lan ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Chinese Patients ◽

The Novel ◽

Micropapillary Pattern

Download Full-text

Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma

BioMed Research International ◽

10.1155/2016/1428271 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Fei Tian ◽

Rui Li ◽

Zhenzhu Chen ◽

Yanting Shen ◽

Jiafeng Lu ◽

...

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Target Genes ◽

Expression Profiles ◽

Major Type ◽

Regulatory Pathways ◽

Normal Tissues ◽

Qrt Pcr ◽

Diagnosis And Prognosis ◽

Tumor Tissues

Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer.

Download Full-text