scholarly journals Genome-wide analysis of the hypoxia-related DNA methylation-driven genes in lung adenocarcinoma progression

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Hongxia Li ◽  
Li Tong ◽  
Hong Tao ◽  
Zhe Liu
Keyword(s):  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Smoking Status ◽  
Disease Free Survival ◽  
Poor Prognostic Factor ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Key Genes ◽  
The Relationship

Abstract Lung adenocarcinoma (LUAD) is a common type of lung cancer with high incidence and poor prognosis. Hypoxia and DNA methylation play important regulatory roles in cancer progression. The purpose of the present study was to explore the relationship between hypoxia and DNA methylation, and to identify key genes for hypoxia-regulated LUAD progression. Hypoxia score (HS) was calculated using the GSVA algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein–protein interaction (PPI) analysis were performed using clusterProfile package, STRING database and Cytoscape software. Kaplan–Meier curves of overall survival (OS) and disease-free survival (DFS) were drawn using R software. Smoking status and cancer stages were significantly associated with LUAD hypoxia, and hypoxia is a poor prognostic factor for LUAD. Compared with HS-low group, 1803 aberrantly methylated DEGs were identified in HS-high group. KEGG analysis showed that the 1803 genes were enriched in the metabolic pathways associated with hypoxia stress, angiogenesis and cancer progression. FAM20C, MYLIP and COL7A1 were identified as the hypoxia-related key genes in LUAD progression, which were regulated by DNA methylation. Hypoxia in LUAD tumor cells led to changes in DNA methylation patterns. In-depth study of the relationship between hypoxia and DNA methylation is helpful to elucidate the mechanism of tumorigenesis, and provides new ideas for LUAD treatment.

Genomic DNA methylation analysis revealed that BLNK is a key potential gene in the regulation of autophagy-related thyroid cancer progression

Genome ◽  
2021 ◽  
Author(s):  
Shengchi Zhang ◽  
Yongzhe Zheng ◽  
Guimin Zhang ◽  
Peng Lin ◽  
Wei Wang
Keyword(s):  
Dna Methylation ◽  
Thyroid Cancer ◽  
Cancer Progression ◽  
Protein Interactions ◽  
Methylation Status ◽  
Expression Change ◽  
Prognostic Analysis ◽  
Key Genes ◽  
New Perspective ◽  
The Relationship

The purpose of this study was to explore the relationship between autophagy and DNA methylation, and to identify key genes for autophagy-regulated thyroid cancer progression. We divided patients with thyroid cancer into high-autophagy score (AS) group and low-AS group based on their AS values. The results found that AS was associated with the distant metastasis of thyroid cancer, and adversely affected prognosis. Then, we screened 359 differently expressed genes (DEGs) with DNA methylation status consistent with gene expression change. Functional classification analysis demonstrated that the 359 DEGs consistent with DNA methylation status were significantly involved in adhesion, migration and differentiation of immune cells. To further screen the key genes in the autophagy-related thyroid cancer progression, we constructed a protein-protein interactions (PPI) network and performed prognostic analysis. B cell linker (BLNK) was identified as the key potential gene affecting autophagy-related thyroid cancer progression. Finally, we verified that BLNK promoted the proliferation of thyroid cancer cells, and BLNK expression was regulated by DNA methylation. Our research provides a new perspective for exploring the relationship between autophagy and DNA methylation during the progression of thyroid cancer, and provides a new target for the treatment of metastatic thyroid cancer.

scholarly journals COL1A1, COL1A2, COL3A1 and DCN are Potential Biomarkers to Predict Progression from Smokers to Suffering from Lung Adenocarcinoma

2020 ◽  
Author(s):  
Jixin Chen ◽  
Shuqi Chen ◽  
Feiye Wang ◽  
Sumei Wang ◽  
Wanyin Wu
Keyword(s):  
Lung Adenocarcinoma ◽  
Single Cell ◽  
Genetic Alterations ◽  
Gene Expression Omnibus ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Expression Atlas ◽  
Targeted Drug ◽  
Key Genes ◽  
Potential Biomarkers

Abstract Background: To explore novel related genes and potential biomarkers that predict progression from smokers to lung adenocarcinoma (LA). Methods: Three datasets from GEO (Gene Expression Omnibus) database were used to identify differentially expressed genes (DEGs) between LA tissue (LAT) and normal tumor adjacent tissue (TAT). The overlap of DEGs could be found and enriched in gene oncology (GO) and pathways to discover the potential biological mechanisms. Protein-protein interaction (PPI) network was applied to find the relationship among proteins. Survival analysis contributed to the definiteness of key genes. The expression of key genes in LA patients who smoke was verified. Furthermore, genetic alterations, co-expression and pathways of key genes were explored. To obtain more information, key genes were further analyzed in immune infiltration, drug target and the distribution of single cell in LA. Results: 245 DEGs were revealed in 3 datasets from GEO. In Kaplan Meier plotter, we found that high expression of COL1A1, COL1A2 and COL3A1 was associated with poorer survival while low expression of DCN was contributed to poorer survival in LAs who smoke. Thus, three up-regulated genes (COL1A1, COL1A2, COL3A1) and one down-regulated gene (DCN) were defined as key genes. Their genetic alterations were more common in female LA smokers and co-expression genes/proteins of them mainly functioned at extracellular matrix. Furthermore, COL1A1, COL1A2, COL3A1 genes had a common targeted drug called Collagenase clostridium histolyticum (DB00048) and DCN gene had a targeted drug called Tromethamine (DB03754). In the Single Cell Expression Atlas of EMBL-EBL, COL3A1 gene was specifically highly expressed in female LA patients with brain metastasis. Conclusions: COL1A1, COL1A2, COL3A1 and DCN could be regarded as novel potential biomarkers that predict progression from smokers to lung adenocarcinoma.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

scholarly journals NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

scholarly journals The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Giuliana Favara ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
The Relationship

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.

scholarly journals The Lung Adenocarcinoma Microenvironment Mining and Its Prognostic Merit

2020 ◽  
Vol 19 ◽  
pp. 153303382097754
Author(s):  
Rongchang Zhao ◽  
Dan Ding ◽  
Wenyan Yu ◽  
Chunrong Zhu ◽  
Yan Ding
Keyword(s):  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Clinicopathological Characteristics ◽  
Survival Prognosis ◽  
Kaplan Meier ◽  
Relationship Of ◽  
Immune Score ◽  
The Relationship ◽  
Kaplan Meier Plotter ◽  
Tumor Topography

Background: As a common pathological type of lung cancer, lung adenocarcinoma (LUAD) is mainly treated by surgery, chemotherapy, targeted therapy and radiotherapy. Although a relatively mature treatment system has been established, there are few studies on the microenvironment of LUAD. Material and Methods: The immune and stromal scores of patients from the LUAD cohort in the TCGA database were obtained by using ESTIMATE. The relationship of immune and stromal scores with the clinicopathological characteristics and overall survival of LUAD patients was assessed by R. GO, KEGG and Cox regression analyses were employed to analyze intersecting genes and to identify reliable prognostic markers. The identified genes were also analyzed in the GEPIA database to assess their correlations with survival, and these relationships were verified with the Kaplan-Meier Plotter database. Results: The immune score was related to the survival time and tumor topography of LUAD patients. There was a significant correlation between stromal score and tumor metastasis. Through multivariate analysis, stage (HR = 1.640, 95% CI = 1.019-2.642, P = 0.042) and risk score (HR = 1.036, 95% CI = 1.026-1.046, P < 0.001). The genes (ARHGAP15, BTLA, CASS4, CLECL1, FAM129C, STAP1, TESPA1, and S100P) showed credible prognostic value in LUAD patients in TCGA through GEPIA database online analysis and verification in the Kaplan-Meier plotter database. Conclusions: In the microenvironment of lung adenocarcinoma, the differentially expressed genes screened by immune score and stromal score have certain value in evaluating the survival/prognosis of patients, as well as the invasion and progression of tumors.

scholarly journals Identification of nine key genes by bioinformatics analysis for predicting poor prognosis in smoking-induced lung adenocarcinoma

2020 ◽  
Vol 9 (2) ◽  
pp. LMT30
Author(s):  
Chuanli Ren ◽  
Weixiu Sun ◽  
Xu Lian ◽  
Chongxu Han
Keyword(s):  
Lung Adenocarcinoma ◽  
Differentially Expressed Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Kaplan Meier ◽  
Key Genes ◽  
Core Genes

Aim: To screen and identify key genes related to the development of smoking-induced lung adenocarcinoma (LUAD). Materials & methods: We obtained data from the GEO chip dataset GSE31210. The differentially expressed genes were screened by GEO2R. The protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape. Finally, core genes were screened. The overall survival time of patients with the core genes was analyzed by Kaplan–Meier method. Gene ontology and Kyoto encyclopedia of genes and genomes bioaccumulation was calculated by DAVID. Results: Functional enrichment analysis indicated that nine key genes were actively involved in the biological process of smoking-related LUAD. Conclusion: 23 core genes and nine key genes among them were correlated with adverse prognosis of LUAD induced by smoking.

Real-world outcome analysis of EGFR-mutated lung adenocarcinoma with brain metastases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13588-e13588
Author(s):  
Feng-Che Kuan ◽  
Wei-Hsun Yang ◽  
Hung-Yi Lai ◽  
Chun-Chieh Huang ◽  
Cheng-Ta Yang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Lung Adenocarcinoma ◽  
Egfr Mutations ◽  
Outcome Analysis ◽  
P Value ◽  
Research Database ◽  
Poor Prognostic Factor ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Egfr Mutated

e13588 Background: BM represent a common problem in EGFR-mutated lung adenocarcinoma. The updated Lung-molGPA elucidates the survival in patients with non-small-cell lung cancer and BM by incorporating the effect of EGFR gene alterations. However, the nature history and differences of prognostic implication between common and uncommon EGFR mutations remain unsolved. Methods: By retrospective analysis of Chang-Gung Research Database (CGRD), patients with EGFR-mutated lung adenocarcinoma and BM were included into analysis of PFS and OS. EGFR mutations were categorized into exon 19 deletions (Del19), exon 21 Leu858Arg substitution (L858R) and uncommon mutations. Kaplan-Meier method was used to estimate survival, and multivariate Cox proportional hazard models was performed to estimate adjusted hazard ratios (HR) and 95% confidence interval (CI). The p-value was set to be statistically significant at 0.05 or less. Results: From April 1, 2014 to June 30, 2015, 269 out of 818 patients with EGFR-mutated lung adenocarcinoma and BM were included, of which 115 patients with Del19, 131 patients with L858R, and 23 patients with uncommon EGFR mutations. The baseline characteristics were balanced in age, gender, KPS, ECM, number of BM, and timing of BM. In comparison with those with L858R, uncommon mutations is a poor prognostic factor for PFS (HR 2.24, 95% CI: 1.34-3.75, p = 0.002). The median PFS of Del 19, L858R, and uncommon EGFR mutations were 10.4, 10.0, and 3.2 months, respectively (log-rank p = 0.03). Besides, the median OS of Del 19, L858R, and uncommon EGFR mutations were 18.1, 17.4, and 12.5 months, respectively (log-rank p = 0.05). In comparison with those treated with gefitinib, afatinib treatment is a good prognostic factor for PFS and OS (PFS, HR 0.57, 95% CI: 0.35-0.94, p = 0.03; OS, HR 0.48, 95% CI: 0.26-0.91, p = 0.03). The median PFS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 11.0, 8.5, and 10.3, respectively (log-rank p = 0.63). In addition, the median OS of those treated with sequential WBRT, concurrent WBRT and TKI alone were 18.7, 15.2, and 18.2 months, respectively (log-rank p = 0.50). Conclusions: Among patients with EGFR-mutated adenocarcinoma, common and uncommon EGFR mutations have distinct natural history and prognostic implications in patients with BM.

scholarly journals Prognostic Impact of Hypoxia-InduciblemiRNA-210in Patients with Lung Adenocarcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Osugi ◽  
Yuka Kimura ◽  
Yuki Owada ◽  
Takuya Inoue ◽  
Yuzuru Watanabe ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Disease Free Survival ◽  
Inverse Correlation ◽  
Prognostic Impact ◽  
Free Survival ◽  
Cox Analysis ◽  
Medical University ◽  
Disease Stages ◽  
The Relationship ◽  
Disease Free

Objective. The aim of this study was to investigate the prognostic value ofMicroRNA-210(miR-210) expression in patients with non-small-cell lung cancer (NSCLC).Methods. We examined themiR-210expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship betweenmiR-210expression and clinicopathological factors as well as histological subtype was statistically analyzed.Results.miR-210expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found betweenmiR-210expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated thatmiR-210expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma.Conclusions. We showed thatmiR-210may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma.

scholarly journals SPP1 Might Be a Novel Prognostic Biomarker for Patients With Malignancy: a Meta-analysis and Sequential Verification Based on Bioinformatic Analysis

2020 ◽  
Author(s):  
Hao-ran Zheng ◽  
Ai-Min Jiang ◽  
Na Liu ◽  
Qian-Qian Ding ◽  
Fu-Mei Zhao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lipid Metabolism ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cochrane Library ◽  
The Relationship

Abstract Background: Several studies have investigated the relationship between secreted phosphoprotein 1 (SPP1) expression level and prognosis of various tumors, but the results are far from conclusive. Therefore, we performed the present meta-analysis to investigate the prognostic value of SPP1 in pan-cancer. Furthermore, a followed confirmation based on The Cancer Genome Atlas (TCGA) database was also performed to verify our results.Methods: We performed a systematic search from PubMed, Embase, Web of Science, and Cochrane Library databases and 19 articles, including 3403 patients and 9 types of tumors, were pooled in our meta-analysis. Overall survival (OS) and disease-free survival (DFS), which correlated with SPP1 expression, were considered as the primary outcome. Subgroup analyses, sensitivity analysis, and publication bias were used to investigate heterogeneity and reliability of the results. Furthermore, we also explored the relationship between SPP1 expression and clinical parameters of tumor patients. Finally, the results were verified with TCGA database and we further explored the relationship between SPP1 expression and tumor immuno-microenvironment (TIME), DNA methylation, and enriched gene pathway.Results: Our meta-analysis showed that high-expressed SPP1 was significantly related to poor OS and DFS in various cancers, especially in liver hepatocellular carcinoma (LIHC). Furthermore, we also identified that the high expression level of SPP1 was significantly correlated with tumor grade. The expression level of SPP1 in the majority of tumor types were much higher than the corresponding normal tissues analyzed from databases. Besides, we also observed that high-expressed SPP1 was related to poor OS and DFS in LIHC, which supported the conclusion of meta-analysis. In addition, high-expressed SPP1 is related to 6 immune cells in TIME and DNA methylation regulatory genes. Ultimately, the results of Gene Set Enrichment Analysis (GSEA) suggested that tumor-related gene sets, such as hypoxia and lipid metabolism, were significantly enriched in high-expressed SPP1 group.Conclusions: SPP1 is high-expressed in various tumor tissues and correlated with poor prognosis. SPP1 might promote cancer invasion and metastasis by affecting tumor grade, TIME, DNA methylation, hypoxia, and lipid metabolism. SPP1 is expected to become a new clinical indicator for tumor detection and prognosis, and provide a new idea for tumor targeted therapy.

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