scholarly journals Elevated Heterogeneous Nuclear Ribonucleoprotein C Expression Correlates With Poor Prognosis in Patients With Surgically Resected Lung Adenocarcinoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Wei Guo ◽  
Qilin Huai ◽  
Guochao Zhang ◽  
Lei Guo ◽  
Peng Song ◽  
...  

BackgroundLung adenocarcinoma (LUAD), as the most common histological subtype of lung cancer, is a high-grade malignancy and a leading cause of cancer-related death globally. Identification of biomarkers with prognostic value is of great significance for the diagnosis and treatment of LUAD. Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an RNA-binding protein “reader” of N6-methyladenosine (m6A) methylation, and is related to the progression of various cancers; however, its role in LUAD is unclear. The aims of this study aims were to study the expression and prognostic value of HNRNPC in LUAD.MethodsThe Oncomine database and gene expression profiling interactive analysis (GEPIA) were used for preliminary exploration of HNRNPC expression and prognostic value in LUAD. LUAD cases from The Cancer Genome Atlas (TCGA) (n = 416) and the Kaplan-Meier plotter database (n = 720) were extracted to study the differential expression and prognostic value of HNRNPC. HNRNPC expression in the National Cancer Center of China (NCC) cohort was analyzed by immunohistochemical staining, and the relationship between HNRNPC expression and survival rate evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Several pathways that were significantly enriched in the HNRNPC high expression group were identified by Gene Set Enrichment Analysis (GSEA).ResultsFive data sets from the Oncomine and GEPIA databases all supported that HNRNPC expression is significantly higher in LUAD than in normal lung tissue. In TCGA cohort, HNRNPC was highly expressed in LUAD tissues and significantly related to age, sex, smoking history, ethnicity, lymph node metastasis, and TNM staging (P < 0.001). High HNRNPC expression was significantly correlated with poor prognosis in the three cohorts (NCC, TCGA, and K-M plotter) (P < 0.05). Multivariate Cox regression analysis showed that HNRNPC expression was an independent prognostic factor in both TCGA and NCC cohorts (P < 0.05). Further, 10 significantly enriched pathways were identified from TCGA data and 118 lung cancer cell lines in CCLE, respectively.ConclusionsHigh HNRNPC expression is significantly related to poor overall survival in patients with LUAD, suggesting that HNRNPC may be a cancer-promoting factor and a potential prognostic biomarker in LUAD.

2021 ◽  
Author(s):  
Sha Tian ◽  
Shang qing Wang ◽  
Piao Zheng ◽  
Xu Zhu ◽  
Huan Han ◽  
...  

Abstract Background: The FK506-binding protein 4 ( FKBP4 ), a tumor-related gene, plays a vital role in tumorigenesis and cancer progression. The study is aimed to clarify the effect of FKBP4 in lung adenocarcinoma (LUAD). Methods: Relying on The Cancer Genome Atlas (TCGA) cohort, the FKBP4 expression difference between LUAD tissues and non-tumor tissues was first detected, and verified with public tissue microarrays (TMAs), clinical LUAD specimen cohort and Gene Expression Omnibus (GEO) cohort. Then, logistic regression analysis and chi-square test were applied to detect the correlation between FKBP4 expression and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression model were utilized to evaluate the effect of FKBP4 expression on survival. Signaling pathways related to LUAD were obtained via employing Gene Set Enrichment Analysis (GSEA). Results: The FKBP4 expression level in LUAD samples was dramatically higher than that in non-tumor samples. High FKBP4 expression in LUAD is associated with gender, pathological stage, T classification, lymph node metastasis and distant metastasis. The Kaplan-Meier curve indicated a poor prognosis for LUAD patients with high FKBP4 expression. Multivariate analysis suggested that the high FKBP4 expression was a vital independent predictor of poor overall survival (OS). GSEA showed that a total of 15 signaling pathways were enriched in samples with high FKBP4 expression phenotype. Conclusions: FKBP4 may be an oncogene in LUAD, and is promised to become a prognostic indicator and therapeutic target for LUAD.


2020 ◽  
Author(s):  
Pengbo Deng ◽  
Rongrong Zhou ◽  
Jinghui Zhang ◽  
Jian An ◽  
Liming Cao

Abstract Background: Available evidence indicates that kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) is an oncogene in skin carcinoma. This study aimed to evaluate the prognostic value of KNSTRN in lung adenocarcinoma (LUAD) underlying the Cancer Genome Atlas (TCGA) database. Methods: The relationship between clinicopathological features and KNSTRN was analyzed with the Wilcoxon signed-rank test and logistic regression. The clinicopathological characteristics associated with overall survival (OS) were evaluated using Cox regression and the Kaplan–Meier method. Gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA) were performed using TCGA data.Results: The KNSTRN expression level was found to be significantly higher in LUAD tissue than in normal lung tissue. Also, it correlated significantly with advanced clinicopathological characteristics. The Kaplan–Meier survival curve revealed a significant relationship of high expression of KNSTRN with poor OS in patients with LUAD. The multivariate Cox regression hazard model demonstrated the KNSTRN expression level as an independent prognostic factor for patients with LUAD. GO and GSEA analyses indicated the involvement of KNSTRN in cell cycle checkpoints, DNA replication, and G2-M checkpoint M phase. Based on ssGSEA analysis, KNSTRN had a positive relationship with Th2 cells and CD56dim natural killer cells. The KNSTRN expression levels in several types of immune cells were significantly different.Conclusion: The findings suggested that the increased expression level of KNSTRN was significantly associated with the progression of LUAD and could also serve as a novel prognostic biomarker for patients with LUAD.


2021 ◽  
Author(s):  
Yong Zhou ◽  
Yongfei Fan ◽  
Ming Lou ◽  
Xiaoshuang Liu ◽  
Yifeng Mao ◽  
...  

Abstract Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. Non-SMC condensin I complex subunit G (NCAPG) plays a significant role in tumor development. This study aimed to analyse the prognostic value and immunotherapy of NCAPG in non-small cell lung cancer. We set up a tissue microarray (containing 140 NSCLC and 10 normal lung tissues) and performed immunohistochemistry to assess NCAPG expression in the tissues of 140 patients. The receiver operating characteristic curves showed the diagnostic value of NCAPG. The prognostic value of NCAPG in NSCLC was assessed using the univariate and multivariate Cox proportional hazards regression models and Kaplan–Meier plots. We analyzed the association between NCAPG and immune infiltration in NSCLC. In addition, NCAPG expression and the degree of immune infiltration were evaluated based on data from TIMER and cumulative survival probability, and gene set enrichment analysis (GSEA) of NACPG was performed. Based on the database analysis and immunohistochemistry, the NCAPG expression was upregulated in patients with lung cancer compared with para cancer controls (p < 0.001). Multifactorial analysis and Kaplan–Meier plots revealed that upregulation of NCAPG expression was an independent factor in the prognosis of NSCLC. Data from CIBERSORT showed a negative correlation between NCAPG and the expression of memory CD4T cells, CD8T cells, dendritic cells, macrophages, mast cells, and NK cells (p < 0.001). GSEA revealed that cell cycle, adhesion and proliferation were significantly enriched in samples with a high NCAPG expression. NCAPG is a novel biomarker of prognosis and is associated with immune cell infiltration in the tumor microenvironment. Thus, it can be a potential target in NSCLC treatment.


2020 ◽  
Vol 10 ◽  
Author(s):  
Yingjing Wang ◽  
Muqi Shi ◽  
Nan Yang ◽  
Xiaoyu Zhou ◽  
Liqin Xu

GPR115, a member of the adhesion G protein-coupled receptor family, is dysregulated in many cancers. However, the expression and function of GRP115 in non-small cell lung cancer (NSCLC) is not clear. Here, we examined the expression pattern, clinical significance, and function of GPR115 in NSCLC by analysis of clinical specimens and human cell lines and bioinformatics analysis. Immunohistochemical analysis of clinical samples showed that GPR115 was significantly upregulated in NSCLC tissues compares with normal lung epithelial tissue (P &lt; 0.05). And GPR115 overexpression is an independent prognostic factor for 5-year overall survival of NSCLC patients [hazard ratio (HR)=1.625, P = 0.008]. Interestingly, higher expression of GPR115 was strongly correlation with differentiation level (P = 0.027), tumor size (P = 0.010), lymph node metastasis (P = 0.022), tumor-node-metastasis stage (P = 0.008), and poor prognosis of lung adenocarcinoma (LUAD, all P = 0.039), but not lung squamous cell carcinoma (LUSC, P &gt; 0.05). Moreover, downregulation of GPR115 by RNA interference in human lung cancer lines inhibited cell proliferation, migration, and invasion. Preliminary bioinformatic analysis confirmed that GPR115 was closely associated with LAMC2 (Spearman correlation coefficient=0.67, P &lt; 0.05), which was accumulated in ECM-receptor interaction and focal adhesion. Consistent with these findings, deceased of GPR115 was associated with E-cadherin, N-cadherin and Vimentin confirmed by western blot. In conclusion, these data suggest that GPR115 may play a role in the tumor growth and metastasis and may have utility as a diagnostic and prognostic marker for LUAD, but not LUSC.


2019 ◽  
Author(s):  
Xu-gang Hu ◽  
De-min Jiao ◽  
You-liang Si ◽  
Jun Chen ◽  
Xia-li Tang ◽  
...  

Abstract Background: Tobacco exposure is the most important risk factor for the occurrence and death of lung cancer. Fibrinogen beta chain (FGB), the most abundant coagulation factor in plasma, is putatively involved in tumor progression. This study aimed to evaluate the expression pattern and prognostic value of FGB in lung adenocarcinoma with tobacco exposure. Methods: FGB expression in lung adenocarcinoma (LUAD) and corresponding normal lung tissues was compared in The Cancer Genome Atlas (TCGA) database. Stratified analysis was conducted to investigate the expression of FGB in LUAD patients with different tobacco exposure. Kaplan-Meier analysis and Cox-regression analysis were performed to evaluate the prognostic significance of FGB. The same survival analyses were conducted in the KM plotter database to validate the prognostic value of FGB. Results: FGB expression was significantly increased in LUAD tissues than in normal tissues (P<0.001). The FGB expression in smoker group was higher than those in non-smoker group (P<0.001). High FGB expression was associated with advanced N stage (P=0.033) and TNM stage (P=0.046). The smoker group possessed higher level of FGB both in LUAD patients without (P=0.003) or (P =0.045) with lymph node metastasis. However, in early TNM stages, the smoker group showed elevated expression of FGB compared with non-smoker group (P=0.0004), and in advanced TNM stages, there was no significant difference between the two groups (P=0.350). In survival analyses, patients with high FGB expression had remarkably worse overall survival (P=0.007) and progression-free survival ((P=0.007) than those with low FGB expression. In smoker group, high level of FGB expression predicted worse OS (P=0.003) and PFS (P=0.029). Cox-regression analysis indicated that FGB was an independent prognostic factor for LUAD patients’ OS (HR= 1.616, P=0.017) and PFS (HR= 1.710, P=0.028). In smoking group, FGB also served as a promising prognostic biomarker for OS (HR= 1.806, P=0.027) and PFS (HR= 2.181, P=0.013). Similar survival curves were generated in the KM plotter cohort. Conclusions: Our study demonstrated that elevated expression of FGB may identify an aggressive subgroup in LUAD with tobacco exposure and serve as an independent prognostic indicator in these patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Wenting Liu ◽  
Kaiting Jiang ◽  
Jingya Wang ◽  
Ting Mei ◽  
Min Zhao ◽  
...  

BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P &lt; 0.05), and associated with patients’ clinical stage, tumor size, and lymphatic metastasis status (all P &lt; 0.01). Kaplan–Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P &lt; 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013–1.044, P &lt; 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130–1.526, P &lt; 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P &lt; 0.0001), low DNA methylation (R = −0.52, P &lt; 0.0001), and downregulation of hsa-miR-30d-3p (R = −0.17, P &lt; 0.001). GNPNAT1 expression was linked to B cells (R = −0.304, P &lt; 0.0001), CD4+T cells (R = −0.218, P &lt; 0.0001), and dendritic cells (R = −0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8625
Author(s):  
Guiping Wang ◽  
Yingying Zhong ◽  
Jiecong Liang ◽  
Zhibin Li ◽  
Yun Ye

Background Pyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis. Methods Firstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. The Kaplan–Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database. Results Pooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and also strongly correlated with worse OS (P = 2.80e−14), PPS (P = 0.022), FP (P = 1.30e−6) and RFS (P = 3.41e−8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs). Conclusion This study confirms that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD.


2020 ◽  
Author(s):  
Dawei Wang ◽  
Youchen Ye ◽  
Tingting Qu ◽  
Zhifang Zhao ◽  
Zenghui Gu ◽  
...  

Abstract Background Osteosarcoma is the most common primary malignant tumor of skeleton in adolescence. Histone deacetylase 2 (HDAC2), a member of class I histone deacetylase, is putatively involved in tumorigenesis of human malignancies. This study aimed to evaluate the expression pattern and prognostic value of HDAC2 in osteosarcoma.Methods Four datasets were obtained from the gene expression omnibus (GEO) database to explore the expression and prognostic value of HDAC2. Level 3 mRNA expression profiles and clinical data were obtained in The Cancer Genome Atlas (TCGA) for validation. Expression pattern of HDAC2 were illustrated in GSE16088, GSE36001 and GSE42352. The prognostic value of HDAC2 was evaluated and validated by Kaplan-Meier analyses, receiver operating characteristic (ROC), concordance index (C-index) and calibration curve in GSE21257 and TCGA. Multivariate Cox regression analysis, nomogram, and decision curve analysis (DCA) were performed to assess the prognosis predictive capability. Protein-protein interaction (PPI) and gene set enrichment analysis (GSEA) were applied to further understand the molecular network and regulatory mechanisms.Results HDAC2 expression was significantly increased in osteosarcoma tissues. High HDAC2 expression was associated with tumor metastasis and chemotherapy efficacy. Kaplan-Meier analysis demonstrated that high HDAC2 predicted worse overall survival. The ROC curve showed good performance in survival prediction. Cox regression demonstrated that HDAC2 could be an independent prognostic indicator. GSEA revealed patients with high HDAC2 expression were enriched with multiple ontological signatures.Conclusions Elevated expression of HDAC2 may identify an aggressive subgroup in osteosarcoma and serve as an independent prognostic indicator in these patients.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Lei Zhang ◽  
Zhe Zhang ◽  
Zhenglun Yu

Abstract Background Lung cancer (LC) is one of the most lethal and most prevalent malignant tumors, and its incidence and mortality are increasing annually. Lung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. Several biomarkers have been confirmed by data excavation to be related to metastasis, prognosis and survival. However, the moderate predictive effect of a single gene biomarker is not sufficient. Thus, we aimed to identify new gene signatures to better predict the possibility of LUAD. Methods Using an mRNA-mining approach, we performed mRNA expression profiling in large LUAD cohorts (n = 522) from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) was performed, and connections between genes and glycolysis were found in the Cox proportional regression model. Results We confirmed a set of nine genes (HMMR, B4GALT1, SLC16A3, ANGPTL4, EXT1, GPC1, RBCK1, SOD1, and AGRN) that were significantly associated with metastasis and overall survival (OS) in the test series. Based on this nine-gene signature, the patients in the test series could be divided into high-risk and low-risk groups. Additionally, multivariate Cox regression analysis revealed that the prognostic power of the nine-gene signature is independent of clinical factors. Conclusion Our study reveals a connection between the nine-gene signature and glycolysis. This research also provides novel insights into the mechanisms underlying glycolysis and offers a novel biomarker of a poor prognosis and metastasis for LUAD patients.


2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Zhixiao Xu ◽  
Chengshui Chen

Background. Lung adenocarcinoma (LUAD) is one of the most life-threatening malignancies. The crucial role of bone morphogenetic protein (BMP)/BMP receptors reveals the significance of exploring BMP protein-related prognostic predictors in LUAD. Methods. The mRNA expression of BMPs/BMP receptors was investigated in LUAD and normal lung tissues. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed, and the prognostic values were assessed by Kaplan-Meier Plotter. Univariate and multivariate Cox regression analyses were executed to ascertain the correlation between overall survival (OS) and the mRNA expression of BMPs/BMP receptors. The receiver operating characteristic (ROC) curves were implemented to evaluate the predictive power of the prognostic model. Then, the prognostic model was validated in the GEO cohort. Furthermore, a nomogram comprising the prognostic model was established. Results. The mRNA expression of BMP2/5/6/R2, ACVRL1, and TGFBR2/3 was lower in LUAD tissues than in normal lung tissues. High expression of BMP2/4/5/R1A/R2, ACVR1/2A/L1, and TGFBR1/3 was associated with better OS, while BMP7 and ACVR1C/2B were associated with poorer OS. Three genes (BMP5, BMP7, and ACVR2A) were screened by univariate and multivariate Cox regression analyses to develop the prognostic model in TCGA. Significantly better survival was observed in LUAD patients with a low-risk score than those with a high-risk score. The ROC curves confirmed the good performance of the prognostic model, then, the prognostic model was validated in the GSE31210 dataset. A nomogram was constructed (AUCs>0.7). And hub genes were further evaluated, including gene set enrichment analysis and immune cell infiltration. Conclusions. BMP5, BMP7, and ACVR2A are potential therapeutic targets in LUAD. The three-gene prognostic model and the nomogram are reliable tools for predicting the OS of LUAD patients.


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