scholarly journals Prognostic significance of CD276 in non-small cell lung cancer

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 805-812
Author(s):  
Changgong Zhang ◽  
Xuezhi Hao

AbstractBackgroundThe expression and significance of CD276 in non-small cell lung cancer (NSCLC) was explored.MethodThe BioGPS database was used to analyze the expression level of CD276 in normal tissues. Studies on the expression of CD276 in NSCLC patients using the Oncomine database. The prognostic roles of CD276 in NSCLC was studied using the Kaplan-Meier plotter database.ResultThe BioGPS database showed CD276 expression in all the human normal tissues. Compared with normal lung tissue, CD276 gene highly expressed in NSCLC tissue at mRNA level (P<0.05). The expression level of CD276 gene was negatively correlated with overall survival (OS) of NSCLC patients. Subgroup analysis showed that CD276 expression level had a significant effect on OS of patients with lung adenocarcinoma, while in squamous cell carcinoma its expression level had no significant effect on OS.ConclusionAccording to the information mined from the tumor gene database, CD276 mRNA was found highly expressed in NSCLC tissue and the expression of CD276 has a significant impact on survival of NSCLC patients, which provides an important theoretical basis for further study of the role of CD276 in the occurrence and development of NSCLC.

2016 ◽  
Vol 38 (6) ◽  
pp. 2389-2400 ◽  
Author(s):  
Li Wang ◽  
Zhenhong Chen ◽  
Li An ◽  
Yajuan Wang ◽  
Zhijian Zhang ◽  
...  

Background/Aims: Long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. However, the role of lncRNA expression in human Non-small cell lung cancer (NSCLC) biology, prognosis and molecular classification remains unknown. Methods: We established the IncRNA profile in NSCLC by re-annotation of microarrays from the Gene expression omnibus database. Quantitative real-time PCR was used to determine expression of LINC00342. Results: 6066 differentially expressed IncRNAs were identified and we found a novel IncRNA, LINC00342 was significantly up-regulated in NSCLC tissues compared with normal tissues. We confirmed the over-expression of LINC00342 in a cohort of NSCLC patients and found LINC00342 expression level was positively correlated with lymph node metastasis and TNM stages. Furthermore, in a large online database of 1942 NSCLC patients, high expression of LINC00342 indicated poor Overall survival (HR = 1.28, 95% CI: 1.13-1.45) and post progression survival (HR = 1.43, 95% CI: 1.09-1.88). Bioinformatics analyses showed that LINC00342 was co-expressed with different protein-coding genes in NSCLC and normal tissues. Additionally, gene set enrichment analyses found that PTEN and P53 pathways genes were enriched in the groups with higher LINC00342 expression level. By small interfering RNAs mediated silence of LINC00342, proliferation ability was significantly inhibited in lung cancer cell line. Conclusion: To summary, our findings indicate that a set of IncRNAs are differentially expressed in NSCLC and we characterized a novel IncRNA, LINC00342 which is significantly up-regulated in NSCLC and could be a prognostic biomarker.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Liu ◽  
Yi Lu ◽  
Wenan Huang ◽  
Zhibo He

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.


2018 ◽  
Vol 71 (7) ◽  
pp. 642-647 ◽  
Author(s):  
Liuwei Gao ◽  
Hua Zhang ◽  
Bin Zhang ◽  
Jinfang Zhu ◽  
Chen Chen ◽  
...  

ObjectiveThe aim of this study was to evaluate the expression of beta-1,3-N-acetylglucosaminyltransferase-3 (B3GNT3) in non-small cell lung cancer (NSCLC) patients and to investigate the relevance of B3GNT3 expression in tumour prognosis.MethodsIn this study, B3GNT3 expression was examined in five pairs of resectable NSCLC tissue by Western blot and in 42 pairs of resectable NSCLC tissue by quantitative real-time PCR (qRT-PCR). Immunohistochemistry and statistical analysis were performed to assess the relationship between B3GNT3 expression scores and clinicopathological parameters, as well as clinical prognosis in a retrospective cohort of 176 NSCLC patients.ResultsBoth B3GNT3 mRNA and protein expression levels were significantly higher in NSCLC tissue than in adjacent normal tissue. In the 176 NSCLC cases, a high B3GNT3 expression level was positively correlated with lymph node metastasis (P<0.001) and advanced TNM stage (P=0.043). Kaplan-Meier analysis indicated that patients with high B3GNT3 expression had significantly lower disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001) than those with low B3GNT3 expression. Moreover, in the multivariate analyses, B3GNT3 expression was an independent prognostic factor for DFS (HR 0.329, 95% CI 0.213 to 0.508, P<0.001) and OS (HR 0.383, 95% CI 0.249 to 0.588, P<0.001).ConclusionsOur study demonstrated that high expression of B3GNT3 was associated with unfavourable DFS and OS in NSCLC patients, suggesting that B3GNT3 might be a potential prognostic biomarker for NSCLC.


2020 ◽  
Author(s):  
Meng Liang ◽  
Linlin Wang ◽  
Chuanhua Cao ◽  
Shimao Song ◽  
Feng Wu

Abstract LncRNA SNHG10 has been characterized as an oncogenic lncRNA in liver cancer. By analyzing TCGA dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC), indicating its involvement in this disease. We then analyzed the role of SNHG10 in NSCLC.Tumor and paired non-tumor tissues were harvested from 62 NSCLC patients. Expression of SNHG10 and miR-21 in tissues was determined by RT-qPCR. Overexpression of SNHG10 or miR-21 in NSCLC cells was achieved and the interaction between them was analyzed. Cell proliferation was analyzed by CCK-8 assay.In this study we found that SNHG10 is downregulated in cancer tissues of NSCLC patients included in this study. High expression level of SNHG10 predicted favorable survival of NSCLC patients. Levels of miR-21 expression were increased in NSCLC and inversely correlated with SNHG10. In NSCLC cells, SNHG10 overexpression led to increased miR-21 gene methylation and decreased miR-21 expression level. In cell proliferation assay, SNHG10 overexpression attenuated the enhancing effect of miR-21 overexpression on cell proliferation. SNHG10 is downregulated in non-small cell lung cancer and predicts poor survival. It may downregulated miR-21 through methylation to suppress cancer cell proliferation.


2020 ◽  
Vol 66 (7) ◽  
pp. 898-903
Author(s):  
Da-Ling Wang ◽  
Peng Yuan ◽  
Ji-Yuan Tian

SUMMARY OBJECTIVE Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) has been reported to be involved in cancer progression. However, the clinical significance of NBAT1 in non-small cell lung cancer (NSCLC) is still unclear. Our present research aimed to explore whether NBAT1 serves as a biomarker for NSCLC prognosis. METHODS The expression of NBAT1 was examined by RT-PCR in tissue samples of 162 NSCLC patients and was compared with the adjacent non-tumor lung specimens. Then the association between NBAT1 expression and clinical-pathological parameters was further evaluated. Survival analysis was performed using the Kaplan-Meier method. The prognostic significance of NBAT1 expression in NSCLC patients was explored by the use of univariate and multivariate analyses. RESULTS NBAT1 expression was prominently decreased in NSCLC tissues compared with matched normal lung specimens (p < 0.01). Moreover, survival analyses indicated that patients with low expression displayed dramatically decreased 5-year overall survival (p = 0.008). CONCLUSIONS NBAT1 expression might contribute to tumor progression and poor prognosis of NSCLC and might be a new therapeutic target in NSCLC.


2018 ◽  
Vol 46 (4) ◽  
pp. 1517-1527 ◽  
Author(s):  
Bojin Zhu ◽  
Yongjin Yan ◽  
Boyun Shao ◽  
Luwen Tian ◽  
Weihua Zhou

Objective To explore the prognostic significance of nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-6 (SIRT6), encoded by the sirtuin 6 ( SIRT6) gene, in a population of Chinese Han patients with non-small cell lung cancer (NSCLC). Methods Cancer tissues and normal lung tissues (>5 cm adjacent to cancer tissue) were collected from Chinese Han patients with NSCLC. Expression levels of SIRT6 and histone H3-acetyl K56 ( H3K56), in cancer and normal lung tissues from patients with NSCLC, were detected by reverse-transcription polymerase chain reaction, Western blot and immunohistochemistry. Correlations between SIRT6 expression and various clinicopathologic features were investigated. Results Out of 86 patients included in the study, mRNA and protein SIRT6 levels were down-regulated in NSCLC tissue versus normal lung tissue, and SIRT6 levels were inversely correlated with H3K56 levels. Positive rates of SIRT6 were significantly correlated with degree of cell differentiation, TNM stage, lymph node metastasis, overall survival and metastasis-free survival. Conclusion Downregulation of SIRT6 expression may promote NSCLC malignancy in the Chinese Han population. SIRT6 may be a potential therapeutic target in Chinese Han patients with NSCLC.


2019 ◽  
Author(s):  
Fengzhou Li ◽  
Shilei Zhao ◽  
Yanwei Cui ◽  
Jiaqi Qiang ◽  
Tao Guo ◽  
...  

Abstract BackgroundCancer-associated fibroblasts (CAFs), the main component of the tumor microenvironment (TME) of NSCLC, are activated by phenotypic transformation into myofibroblasts. α,1,6-fucosyltransferase (FUT8), the key enzyme catalyzing core α,1,6-fucosylation (CF), plays important roles in multiple malignancies. In the current study, we investigated the functions and mechanism of CF mediated by FUT8 in CAFs in NSCLC through bioinformatics analysis, retrospective clinical studies and in vitro/in vivo laboratory experiments.MethodsBioinformatics was used to reveal the relationship between FUT8 and CAFs. Resected specimens, clinical data and prognostic information from 135 NSCLC patients were analyzed to assess the prognostic value of FUT8 in CAFs. Primary CAFs and normal lung fibroblasts were extracted from NSCLC patients and cocultured with NSCLC cell lines in a novel noncontact coculture device produced by 3D printing. In vivo, CAF/NSCLC coinjection tumorigenesis assay was performed in nude mice to study the function of FUT8/CF in TME. The mechanisms of FUT8/CF in CAFs regulating the cocultured NSCLC cells were investigated in cell and molecular experiments. ResultsFUT8 in CAFs is an independent risk factor for prognosis. FUT8/CF in CAFs is essential for CAFs to maintain their ability to promote NSCLC. FUT8/CF in CAFs is responsible for the cancer-promoting capacities of CAFs and lead to a malignant tumor microenvironment. CF modification enhances tyrosine phosphorylation of EGFR in CAFs, which causes activation of downstream signalings of EGFR and maintains cancer-promoting properties of CAFs.ConclusionFUT8 regulates cancer-promoting capacities of CAFs via the modification of EGFR CF in non-small cell lung cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xianghan Li ◽  
Yiran Zou ◽  
Teng Li ◽  
Thomas K. F. Wong ◽  
Ryan T. Bushey ◽  
...  

BackgroundSingle nucleotide polymorphisms (SNPs) are often associated with distinct phenotypes in cancer. The present study investigated associations of cancer risk and outcomes with SNPs discovered by whole exome sequencing of normal lung tissue DNA of 15 non-small cell lung cancer (NSCLC) patients, 10 early stage and 5 advanced stage.MethodsDNA extracted from normal lung tissue of the 15 NSCLC patients was subjected to whole genome amplification and sequencing and analyzed for the occurrence of SNPs. The association of SNPs with the risk of lung cancer and survival was surveyed using the OncoArray study dataset of 85,716 patients (29,266 cases and 56,450 cancer-free controls) and the Prostate, Lung, Colorectal and Ovarian study subset of 1,175 lung cancer patients.ResultsWe identified 4 SNPs exclusive to the 5 patients with advanced stage NSCLC: rs10420388 and rs10418574 in the CLPP gene, and rs11126435 and rs2021725 in the M1AP gene. The variant alleles G of SNP rs10420388 and A of SNP rs10418574 in the CLPP gene were associated with increased risk of squamous cell carcinoma (OR = 1.07 and 1.07; P = 0.013 and 0.016, respectively). The variant allele T of SNP rs11126435 in the M1AP gene was associated with decreased risk of adenocarcinoma (OR = 0.95; P = 0.027). There was no significant association of these SNPs with the overall survival of lung cancer patients (P &gt; 0.05).ConclusionsSNPs identified in the CLPP and M1AP genes may be useful in risk prediction models for lung cancer. The previously established association of the CLPP gene with cancer progression lends relevance to our findings.


2021 ◽  
Author(s):  
Fei Wang ◽  
Chong Yuan ◽  
Yanfang Yang ◽  
Bo Liu ◽  
Hezhen Wu

Abstract Non-small cell lung cancer (NSCLC) is one of the most malignant tumors with the fastest increasing incidence and mortality rate, but the etiology of NSCLC is still not clear. Most of lncRNAs have some structural similarities with mRNAs, suggesting that miRNAs negatively regulate the expression of lncRNAs to affect the occurrence and development of tumor. Therefore, system bioinformatics was used to explore the potential biomarkers and possible pathogenesis of NSCLC in this study. Firstly, all the clinical information and transcriptome data were downloaded from GEO and TCGA databases. R language was used to analyze the differentially expressed genes (DEGs) in NSCLC and normal lung tissues. Then, 50 overlapped DEGs were obtained via Venn database, including 10 down-regulated mRNAs and 40 down-regulated mRNAs. Secondly, the top 20 DEGs were selected for KEGG pathway and GO enrichment analysis. After screening 4 HUB genes related to the survival and prognosis of NSCLC patients, their prognosis models were established. Meanwhile, HUB genes related miRNAs and lncRNAs were screened. Finally, a mRNA-miRNA-lncRNA network related to the survival and prognosis of NSCLC patients was established, including 4 up-regulated mRNAs, 3 up-regulated miRNAs, 10 down-regulated miRNAs, 6 up-regulated lncRNAs and 19 down-regulated lncRNAs. Subject terms: Non-small cell lung cancer, mRNA-miRNA-lncRNA, pathogenesis, prognostic biomarkers.


2018 ◽  
Vol 150 (4) ◽  
pp. 346-352 ◽  
Author(s):  
Stephen Young ◽  
Christen Griego-Fullbright ◽  
Aaron Wagner ◽  
Amanda Chargin ◽  
Bruce K Patterson ◽  
...  

Abstract Objectives We report on the validity of a fully quantitative technology to determine tumor cells’ PD-L1 expression compared with a standard immunohistochemical (IHC) assay in non–small cell lung cancer. Methods Nineteen fresh tissue specimens were processed into single-cell suspensions using the IncellPREP Kit. Cells were treated with the OncoTect iO Lung Assay, which quantitatively assessed tumor-infiltrating lymphocytes (TILs), DNA content, and PD-L1 expression on diploid and aneuploid tumor populations. Results Comparison of the OncoTect iO Lung Assay with IHC revealed a concordance of 95% overall (negative percent agreement, 97%; positive percent agreement, 89%). PD-L1 expression varied depending on the DNA content. The number of TILs and antigen-presenting cells (APCs) was significantly decreased in tumor compared with normal lung tissue. Conclusions The nonsubjective OncoTect iO Lung Assay has been shown to be at least as accurate and sensitive as IHC for the detection of PD-L1 expression while providing additional information to guide treatment.


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