scholarly journals Prognostic Value of Telomeric Zinc Finger-Associated Protein Expression in Adenocarcinoma and Squamous Cell Carcinoma of Lung

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1223
Author(s):  
Gun-Jik Kim ◽  
Jae-Ho Lee ◽  
Mincheol Chae ◽  
Deok-Heon Lee

Background and Objectives: Telomeric zinc finger-associated protein (TZAP) is a telomere regulation protein, previously known as ZBTB48. It binds preferentially to elongated telomeres, competing with telomeric repeat factors 1 and 2. TZAP expression may be associated with carcinogenesis, however; this study has not yet been performed in lung cancer. In this study, we examined the clinicopathological and prognostic values of TZAP expression in non-small cell lung cancer (NSCLC). Materials and Methods: Data were collected from The Cancer Genome Atlas. The clinical and prognostic values of TZAP for NSCLC were examined in adenocarcinoma (AD) and squamous cell carcinoma (SCC). Results: TZAP expression significantly increased in NSCLC tissues compared with normal tissues. In AD, TZAP expression was lower in patients with higher T stage (p = 0.005), and was associated with lymph node stage in SCC (p = 0.005). Survival analysis showed shorter disease-free survival in AD patients with lower TZAP expression (p = 0.047). TZAP expression did not have other clinical or prognostic value for AD and SCC. Conclusions: TZAP expression is a potential prognostic marker for NSCLC, especially in patients with AD.

Author(s):  
Bing Liu ◽  
Yuan Liu ◽  
Jingfeng Zou ◽  
Menglin Zou ◽  
Zhenshun Cheng

Background: Smoking participates in pathogenesis of lung cancer. Long non-coding RNAs (lncRNAs) play some specific roles during development of lung cancers. Objective: To investigate effects of smoking on lncRNA alterations in lung cancer. Methods: There are 522 lung adenocarcinoma (LUAD) and 504 lung squamous cell carcinoma (LUSC) participants. Clinical and lncRNA genetic data were downloaded from The Cancer Genome Atlas (TCGA) database. LncRNA alterations were analyzed in lung cancer patients. Smoking category and packs were evaluated. Correlations between smoking and LncRNA alterations were analyzed. Kaplan-Meier analysis was performed to determine overall survival and disease free survival. Results: There are more non-smokers in LUSC than in LUAD. In both LUAD and LUSC, smoking could increase total mutation counts and fraction of copy number alterations. Smoking index positively correlated with total mutations in LUAD, but not in LUSC. Smoking could trigger lncRNA alterations both in LUAD and LUSC. Smoking regulated different lncRNA between male and female. EXOC3-AS1 and LINC00603 alterations were positively correlated with smoking index in male LUAD smokers. In female LUAD smokers, smoking index was positively correlated with SNHG15, TP53TG1 and LINC01600 and negatively with LINC00609 and PTCSC3. In both male and female LUSC patients, smoking increased or decreased several lncRNA alterations. DGCR5 alteration increased in male LUSC than in female LUSC patients. In female LUSC patients, LOH12CR2 alteration was positively correlated with smoking index. Conclusions: Smoking promoted LUAD and LUSC development by affecting different lncRNA alterations in different genders.


Author(s):  
Chang-Qing Zhang ◽  
Xue-Bin Wang ◽  
Shu-Ping Li ◽  
Guo-Ying Miao ◽  
Rong Wang ◽  
...  

IntroductionThis study aimed to explore the potential genetic and epigenetic mechanisms associated with IDO1 mRNA dysregulation in esophageal cancer (ESCA).Material and methodsData from The Cancer Genome Atlas (TCGA)-ESCA and The Genotype-Tissue Expression (GTEx) project were obtained for analysis. Subgroup analysis was performed in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ESAD) respectively.ResultsIDO1 expression was significantly upregulated in ESAD and ESCC tissues than in normal esophagus. Although gene-level copy number alterations were common in both ESAD and ESCC, they were not associated with IDO1 dysregulation. Among 3 CpG sites (cg10262052 and cg08465774 in promoter and cg24188163 in gene body) in IDO1 gene locus examined, only cg10262052 was hypomethylated in cancerous tissues than in normal tissues in ESAD. All 3 sites showed significantly different methylation in ESCC than in normal tissues, among which cg10262052 and cg08465774 were hypomethylated, while cg24188163 was hypomethylated. Correlation analysis confirmed negative correlations between cg10262052/cg08465774 methylation and IDO1 expression while cg24188163 methylation was positively correlated with IDO1 expression (Pearson’s r=0.45) in ESCC patients. Genomic study confirmed that cg24188163 is in the flanking region of an intragenic promoter of IDO1. IDO1 expression had an independent prognostic value in terms of OS in ESCC patients (HR: 1.183, 95%CI: 1.025-1.367, p=0.022), but was not a risk factor of unfavorable OS in ESAD patients.ConclusionsIDO1 mRNA upregulation was associated with both promoter hypomethylation and gene body hypermethylation in ESCC. Its expression has a specific prognostic value in terms of OS in ESCC, but not in ESAD patients.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5623
Author(s):  
Ting-Wen Chen ◽  
Kai-Ping Chang ◽  
Chun-Chia Cheng ◽  
Cheng-Yi Chen ◽  
Shu-Wen Hong ◽  
...  

Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Liyan Hou ◽  
Yingbo Li ◽  
Ying Wang ◽  
Dongqiang Xu ◽  
Hailing Cui ◽  
...  

In this study, we investigated the potential prognostic value of ubiquitin-conjugating enzyme E2D1 (UBE2D1) RNA expression in different histological subtypes of non-small-cell lung cancer (NSCLC). A retrospective study was performed by using molecular, clinicopathological, and survival data in the Cancer Genome Atlas (TCGA)—Lung Cancer. Results showed that both lung adenocarcinoma (LUAD) (N=514) and lung squamous cell carcinoma (LUSC) (N=502) tissues had significantly elevated UBE2D1 RNA expression compared to the normal tissues (p<0.001 and p=0.036, respectively). UBE2D1 RNA expression was significantly higher in LUAD than in LUSC tissues. Increased UBE2D1 RNA expression was independently associated with shorter OS (HR: 1.359, 95% CI: 1.031–1.791, p=0.029) and RFS (HR: 1.842, 95% CI: 1.353–2.508, p<0.001) in LUAD patients, but not in LUSC patients. DNA amplification was common in LUAD patients (88/551, 16.0%) and was associated with significantly upregulated UBE2D1 RNA expression. Based on these findings, we infer that UBE2D1 RNA expression might only serve as an independent prognostic indicator of unfavorable OS and RFS in LUAD, but not in LUSC.


2019 ◽  
Vol 276 (5) ◽  
pp. 1487-1492 ◽  
Author(s):  
Bernhard J. Jank ◽  
Lorenz Kadletz ◽  
Julia Schnöll ◽  
Edgar Selzer ◽  
Christos Perisanidis ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiguo Liu ◽  
Hongyan Liu ◽  
Qian Dong ◽  
Hongyu Li ◽  
Bin Zhang ◽  
...  

Abstract Background The gasdermin E gene (GSDME, also known as DFNA5) is mutated in familial aging-related hearing loss. Recent studies have also revealed that the expression of DFNA5 is suppressed in many cancer types; however, little is known about the function of DFNA5 in head and neck squamous cell carcinoma (HNSCC). Accordingly, the aim of the present study was to evaluate the expression of DFNA5 and explore its prognostic value in HNSCC. Result We used a set of bioinformatics tools, including Oncomine, TIMER, TISIDB, cBioPortal, and GEPIA, to analyze the expression of DFNA5 in patients with HNSCC from public databases. Kaplan-Meier plotter was used to evaluate the potential prognostic significance of DFNA5. DFNA5 mRNA levels were significantly higher in HNSCC tissues than in normal tissues, and high DFNA5 expression was correlated with worse survival. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that DFNA5 expression has a strong positive correlation with cell adhesion and the integrin signaling pathway, whereas its expression was negatively correlated with the levels of infiltrating B cells (cor = − 0.223, P = 8.57e-07) and CD8 T cells (cor = − 0.223, P = 2.99e-07). Conclusion This study demonstrates that DFNA5 expression has prognostic value for HNSCC patients. Moreover, these results suggest that regulation of lymphocyte infiltration is the mechanism underlying the function of DFNA5 in HNSCC.


2020 ◽  
Vol 19 ◽  
pp. 153303382098578
Author(s):  
Zhibin Jing ◽  
Sitong Guo ◽  
Peng Zhang ◽  
Zheng Liang

Objective: This study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC). Methods: The mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. Results: There were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC. Conclusion: This study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0259447
Author(s):  
Bingqing Sun ◽  
Hongwen Zhao

Lung cancer is characterized by high morbidity and mortality rates, and it has become an important public health issue worldwide. The occurrence and development of tumors is a multi-gene and multi-stage complex process. As an oncogene, ribosomal oxygenase 2 (RIOX2) has been associated with a variety of cancers. In this article, we analyzed the correlation between RIOX2 expression and methylation in lung cancer based on the databases including the cancer genome atlas (TCGA) (https://portal.gdc.cancer.gov/) and the gene expression omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/). It was found that RIOX2 is highly expressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues, whose expression is negatively correlated with its methylation level. In this regard, methylation at cg09716038, cg14773523, cg14941179, and cg22299097 had a significant negative correlation with RIOX2 expression in LUAD, whereas in LUSC, methylation at cg09716038, cg14773523, cg14941179, cg22299097, cg05451573, cg10779801, and cg23629183 is negatively correlated with RIOX2 expression. According to the analysis based on the databases, RIOX2 gene could not be considered as the independent prognostic biomarker in lung adenocarcinoma or squamous cell lung cancer. However, the molecular mechanism of RIOX2 gene in the development of lung cancer may be helpful in improving lung cancer therapy.


2020 ◽  
Author(s):  
Binglin Chen ◽  
Wenqi Liu ◽  
Chunxiao Liang ◽  
Feifeng Lan

Abstract Background: TGM2 is a functionally diverse molecule that has multiple roles in mediating signal transduction and inflammation. However, the prognostic value of TGM2 and its correlation with tumor-infiltrating immune cells in lung squamous cell carcinoma (LUSC) remains elusive. Methods: Datasets of LUSC were downloaded from The Cancer Genome Atlas (TCGA) to analyze the expression of TGM2 in LUSC. Then, Univariable survival and Multivariate Cox analysis was used to analyze the survival effect of several clinical characteristics. The influence of TGM2 on survival of LUSC patients was evaluated by Gene Expression Profiling Interactive Analysis (GEPIA). The relationship between TGM2 and tumor-infiltrated immune cells was analyzed using the Tumor Immune Estimation Resource (TIMER).Results: TGM2 expression was remarkably lower in LUSC tissues than in the corresponding normal tissues. Low TGM2 expression was correlated with better OS in LUSC. Multivariate survival analysis demonstrated that high TGM2 expression was an independent risk factor for OS.TGM2 expression was significantly positively associated with infiltrating levels of macrophages, meanwhile was strongly correlated with various markers of immune cells, especially tumor-associated macrophages (TAMs) and T-regulatory cells (Tregs).Conclusions: TGM2 is a prognostic biomarker and correlated with immune infiltrates in LUSC.


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