scholarly journals OLFML2B Is a Robust Prognostic Biomarker in Bladder Cancer Through Genome-Wide Screening: A Study Based on Seven Cohorts

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiaxing Lin ◽  
Xiao Xu ◽  
Tianren Li ◽  
Jihang Yao ◽  
Meng Yu ◽  
...  

BackgroundBladder cancer lacks useful and robust prognostic markers to stratify patients at risk. Our study is to identify a robust prognostic marker for bladder cancer.MethodsThe transcriptome and clinical data of bladder cancer were downloaded from multiple databases. We searched for genes with robust prognosis by Kaplan-Meier analysis of the whole genome. CIBERSORT and TIMER algorithm was used to calculate the degree of immune cell infiltration.ResultsWe identified OLFML2B as a robust prognostic marker for bladder cancer in five cohorts. Kaplan-Meier analysis showed that patients with a high level of OLFML2B expression had a poor prognosis. The expression of OLFML2B increased with the increase of stage and grade. We found that patients with high expression of OLFML2B still had a poor prognosis in two small bladder cancer cohorts. OLFML2B also has the prognostic ability in ten other tumors, and the prognosis is poor in high expression. The correlation analysis between OLFML2B and immune cells showed that it was positively correlated with the degree of macrophage infiltration and highly co-expressed with tumor-associated macrophage markers. Finally, the Wound-healing assay and Colony formation assay results showed that the migration and proliferation ability of bladder cancer cell lines decreased after the knockdown of OLFML2B.ConclusionsIn summary, OLFML2B is a robust risk prognostic marker, and it can help patients with bladder cancer improve individualized treatment.

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  

Abstract Background Breast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.Methods At first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.Results The results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC. conclusions In summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.


2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  

Abstract BackgroundBreast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.MethodsAt first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.ResultsThe results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC.ConclusionIn summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.


2021 ◽  
Author(s):  
Zhiqiang Yao ◽  
Jiajia Zhang ◽  
Chaohu Chen ◽  
Pan Li ◽  
Jinlong Cao ◽  
...  

Abstract Background: Bladder cancer (BLCA) is the most common malignancy of urinary system with a high recurrence rate. We aimed to explore the relationship between cathepsin V (CTSV) expression and prognosis in patients with bladder cancer.Methods: The RNA-Seq gene expression data and corresponding clinical information with BLCA were downloaded from TCGA database. The gene expression profiles of GSE13507 and GSE133624 were downloaded from GEO database. BLCA patients were divided into high and low expression group according to the cutoff value of CTSV expression. The relationship between clinicopathologic characteristics and CTSV expression was analyzed with the Wilcoxon signed-rank test and logistic regression. Kaplan-Meier analysis and Cox regression were used to analyze the relationship between overall survival and clinicopathologic characteristics. Gene set enrichment analysis (GSEA) was utilized to identify enriched KEGG pathway.Results: High expression of CTSV was significantly correlated with pathological grade (OR = 1.662 for low vs. high), clinical stage (OR = 1.589 for I-II vs. III-IV), status (OR = 1.435 for normal vs. tumor), T stage (OR = 1.589 for T1-2 vs. T3-4), and M stage (OR = 4.499 for M0 vs M1). The expression of CTSV was significantly increased in BLCA compared with normal tissue (P < 0.001). Kaplan-Meier survival analysis showed that BLCA patients with high expression of CTSV had a poorer prognosis than low expression of CTSV patients (P = 0.0016). Univariate Cox analysis showed that high expression of CTSV was significantly associated with poorer overall survival (HR:1.662, 95%CI:1.209-2.286, P = 0.002). Multivariate Cox regression showed that high expression of CTSV was an independent risk factor for poor prognosis in BLCA patients (HR: 1.495, 95%CI: 1.069-2.089, P = 0.019). We also used the GSE13507 and GSE133624 to verify whether CTSV was differently expressed in bladder cancer tissues and normal tissues. The results showed that CTSV expression was significantly increased in BLCA patients (P < 0.05). Finally, GSEA was used to show 22 enriched signaling pathways in a high phenotype.Conclusion: High expression of CTSV in bladder cancer is associated with poor prognosis and may serve as a new biomarker. In addition, the chemokine signaling pathway, MAPK signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway, tight Junction and cell adhesion molecules may be the key pathway regulated by CTSV in BLCA.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Li ◽  
Xiaowei Chen ◽  
Xueju Hu ◽  
Yan Shen ◽  
Rui Xu ◽  
...  

BackgroundNitric oxide (NO) and cyclic guanosine phosphate (cGMP) play important roles in blood pressure regulation, neurotransmitter delivery, renal function, and tumorigenesis and development. The intermediate link of this signaling pathway, soluble guanylyl cyclase (sGC), is particularly important. However, the role of the GUCY1A2 gene encoding the sGC α2 subunit is unknown.MethodsGene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. After screening for GUCY1A2 expression, the expression differences between gastric cancer (GC) tissues and adjacent noncancerous tissues were determined using R software. Quantitative real-time polymerase chain reaction (qRT-PCR) and meta-analysis were used to verify the result. The correlation between the expression of GUCY1A2 and clinicopathological parameters was explored by logistic regression. Then, Kaplan-Meier survival analysis and the Cox proportional hazards regression were used to evaluate the relationship between the expression of GUCY1A2 and the survival of GC patients. Finally, gene set enrichment analysis (GSEA) was used to explore and analyze the GC-related signaling pathways affected by high GUCY1A2 expression.ResultsWe found that GUCY1A2 was highly expressed in GC tissues compared to adjacent noncancerous tissues (P &lt; 0.001). qRT-PCR (P &lt; 0.001) and meta-analysis (SMD = 0.65, 95% CI: 0.20-1.10) confirmed the difference in GUCY1A2 expression. Logistic regression analysis showed that high expression of GUCY1A2 was associated with histological grade (OR=1.858 for poor vs. well or moderate, P = 0.004) and T stage (OR = 3.389 for T3 vs. T1, P = 0.025; OR = 3.422 for T4 vs. T1, P = 0.028). Kaplan-Meier curves indicated that GC patients with high expression of GUCY1A2 had a poor prognosis than that of patients with low expression. Univariate analysis indicated that GUCY1A2 and some clinicopathological parameters, such as age, pathological stage, and TNM stage, may predict poor prognosis. Multivariate analysis further confirmed that GUCY1A2 was an independent prognostic marker (HR = 1.699; 95%CI, 1.175-2.456; P = 0.005). GSEA showed that the high GUCY1A2 phenotype is significantly enriched for tumor-associated signaling pathways.ConclusionsGUCY1A2 is highly expressed in GC and may be used as a potential prognostic marker.


2020 ◽  
Author(s):  
Sizhe Hu ◽  
Peipei Li ◽  
Chenying Wang ◽  
Xiyong Liu

Abstract Background: BGN (biglycan) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer.Material and Methods: Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets( n= 64, n=432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Bioinformatic analysis predicted the putative transcription factors of BGN.Results: For gastric cancer, the mRNA expression level of BGN in tumor tissues was significantly higher than that in normal tissues. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN significantly enriched metastasis and poor prognosis gene signatures, revealing that BGN might be associated with cell proliferation, poor differentiation, high invasiveness of gastric cancer. Meanwhile, the putative transcription factors, including AR, E2F1, and TCF4, weres predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ying Chen ◽  
Bo Zhao ◽  
Xiaohu Wang

Abstract Background Osteosarcoma is a rare malignant bone tumor in adolescents and children. Poor prognosis has always been a difficult problem for patients with osteosarcoma. Recent studies have shown that tumor infiltrating immune cells (TIICs) are associated with the clinical outcome of osteosarcoma patients. The aim of our research was to construct a risk score model based on TIICs to predict the prognosis of patients with osteosarcoma. Methods CIBERSORTX algorithm was used to calculate the proportion of 22 TIIC types in osteosarcoma samples. Kaplan-Meier curves were drawn to investigate the prognostic value of 22 TIIC types. Forward stepwise approach was used to screen a minimal set of immune cell types. Multivariate Cox PHR analysis was performed to construct an immune risk score model. Results Osteosarcoma samples with CIBERSORTX output p value less than 0.05 were selected for research. Kaplan-Meier curves indicated that naive B cells (p = 0.047) and Monocytes (p = 0.03) in osteosarcoma are associated with poor prognosis. An immune risk score model was constructed base on eight immune cell types, and the ROC curve showed that the immune risk score model is reliable in predicting the prognosis of patients with osteosarcoma (AUC = 0.724). Besides, a nomogram model base on eight immune cell types was constructed to predict the survival rate of patients with osteosarcoma. Conclusions TIICs are closely related to the prognosis of osteosarcoma. The immune risk score model based on TIICs is reliable in predicting the prognosis of osteosarcoma.


2021 ◽  
Author(s):  
Yaqiong Fan ◽  
Yichen Peng ◽  
Feng Chen ◽  
Wenbin Li

Abstract Background: Interleukin-10 receptor B (IL10RB) is a subunit of the interleukin-10 receptor. As an important part of the interleukin-10 signaling pathway, IL10RB plays an essential role in the regulation of the immune response. However, studies of IL10RB in glioma are rare. The present study aimed to investigate the potential role of IL10RB in glioma.Methods: 611 glioma samples in TCGA dataset and 310 glioma samples in CGGA dataset were download and organized, then analyzed the clinical expression characteristics and prognostic value of IL10RB as well as its correlation with immune cell infiltration in these samples using R. Results: IL10RB expression was significantly higher in the glioma tissues than in the normal tissues and increased in gliomas, especially with malignant phenotype. The Kaplan-Meier survival analysis and Cox regression analysis indicated that IL10RB was significantly associated with poor prognosis in patients with glioma and could be used as an independent prognostic marker. Further functional analysis suggested that IL10RB was involved in immune responses, and high expression of IL10RB in the glioma tissue resulted in more infiltrated immune cells, especially macrophages. Moreover, IL10RB was found to be strongly correlated with marker genes of tumor-associated macrophages (TAMs) and M2 macrophages, but low or even no correlation with marker genes of M1 macrophages. In addition, there was also a significant association between IL10RB and immune checkpoints that suppress effective antitumor immune responses.Conclusions: Our results demonstrated that high expressed IL10RB was associated with the malignant progression of gliomas and poor prognosis, and it might be involved in the polarization of macrophages which play a crucial role in the immunosuppressive response of gliomas.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yujia Xiong ◽  
Mingxuan Li ◽  
Jiwei Bai ◽  
Yutao Sheng ◽  
Yazhuo Zhang

Glioma is the most common primary intracranial malignant tumor in adults. Although there have been many efforts on potential targeted therapy of glioma, the patient’s prognosis remains dismal. Methyltransferase Like 7B (METTL7B) has been found to affect the development of a variety of tumors. In this study, we collected RNA-seq data of glioma in CGGA and TCGA, analyzed them separately. Then, Kaplan-Meier survival analysis, univariate and multivariate Cox analysis, and receiver operating characteristic curve (ROC curve) analysis were used to evaluate the effect of METTL7B on prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) enrichment analyses were used to identify the function or pathway associated with METTL7B. Moreover, the ESTIMATE algorithm, Cibersort algorithm, Spearman correlation analysis, and TIMER database were used to explore the relationship between METTL7B and immunity. Finally, the role of METTL7B was explored in glioma cells. We found that METTL7B is highly expressed in glioma, and high expression of METTL7B in glioma is associated with poor prognosis. In addition, there were significant differences in immune scores and immune cell infiltration between the two groups with different expression levels of METTL7B. Moreover, METTL7B was also correlated with immune checkpoints. Knockdown of METTL7B revealed that METTL7B promoted the progression of glioma cells. The above results indicate that METTL7B affects the prognosis of patients and is related to tumor immunity, speculating that METTL7B may be a new immune-related target for the treatment of glioma.


2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Yulan Bu ◽  
Lihua Zhang ◽  
Xiaolin Ma ◽  
Rui Wang ◽  
Xuecheng Zhang ◽  
...  

Background. Emerging studies support the oncogenic role of WD repeat domain 62 (WDR62) in few tumors, while no pan-cancer analysis is available. In this study, we analyzed systematically the oncogenic role of WDR62 across a series of human tumors based on bioinformatic data mining. Methods. The expression level of WDR62 was analyzed via GEPIA2, TIMER, UALCAN, and StarBase databases. The prognostic role was analyzed via GEPIA2, TIMER, UALCAN, StarBase, TISIDB, TCGA portal, Kaplan-Meier Plotter, and PrognoScan databases. Then, we explored the causes for WDR62 abnormal expression via TCGA portal and UALCAN databases. Subsequently, the STRING and GeneMANIA databases were used to find the interactive networks for WDR62. Furthermore, we analyzed the correlation between WDR62 expression and immune features via TIMER and TISIDB databases. Results. We found that WDR62 was significantly upregulated in most of the tumors and correlated with poor prognosis mainly in 6 candidate tumors—BLCA, BRCA, KIRC, KIRP, LIHC, and LUAD. Abnormal WDR62 expression may be probably attributed to TP53 mutation and promoter DNA methylation. Relative network analysis demonstrated that WDR62 was mainly involved in MAPK and toll-like receptor signaling pathway. WDR62 expression was associated with various immune cell infiltrations, especially cancer-associated fibroblasts (CAF) and T cell regulatory (Treg) cells, and was markedly correlated with poor prognosis. Moreover, WDR62 expression was closely associated with the expression of some immunomodulators such as PD-L1 and has a significant prognostic value. Conclusions. Our study revealed that WDR62 could serve as a diagnostic and prognostic biomarker for several cancers. Importantly, WDR62 was closely associated with various immune cell infiltration, and to a certain extent, it can predict the effect of immunotherapy in particular PD1/PD-L1 inhibitors. Our pan-cancer study provided useful information on the oncogenic role of WDR62, contributing to further exploring the underlying mechanisms.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Chen ◽  
Jiayi Shen ◽  
Dongsheng Cai ◽  
Tiemin Wei ◽  
Renyi Qian ◽  
...  

Abstract Background Estimated plasma volume status (ePVS) has been reported that associated with poor prognosis in heart failure patients. However, no researchinvestigated the association of ePVS and prognosis in patients with acute myocardial infarction (AMI). Therefore, we aimed to determine the association between ePVS and in-hospital mortality in AMI patients. Methods and results We extracted AMI patients data from MIMIC-III database. A generalized additive model and logistic regression model were used to demonstrate the association between ePVS levels and in-hospital mortality in AMI patients. Kaplan–Meier survival analysis was used to pooled the in-hospital mortality between the various group. ROC curve analysis were used to assessed the discrimination of ePVS for predicting in-hospital mortality. 1534 eligible subjects (1004 males and 530 females) with an average age of 67.36 ± 0.36 years old were included in our study finally. 136 patients (73 males and 63 females) died in hospital, with the prevalence of in-hospital mortality was 8.9%. The result of the Kaplan–Meier analysis showed that the high-ePVS group (ePVS ≥ 5.28 mL/g) had significant lower survival possibility in-hospital admission compared with the low-ePVS group (ePVS < 5.28 mL/g). In the unadjusted model, high-level of ePVS was associated with higher OR (1.09; 95% CI 1.06–1.12; P < 0.001) compared with low-level of ePVS. After adjusted the vital signs data, laboratory data, and treatment, high-level of ePVS were also associated with increased OR of in-hospital mortality, 1.06 (95% CI 1.03–1.09; P < 0.001), 1.05 (95% CI 1.01–1.08; P = 0.009), 1.04 (95% CI 1.01–1.07; P = 0.023), respectively. The ROC curve indicated that ePVS has acceptable discrimination for predicting in-hospital mortality. The AUC value was found to be 0.667 (95% CI 0.653–0.681). Conclusion Higher ePVS values, calculated simply from Duarte’s formula (based on hemoglobin/hematocrit) was associated with poor prognosis in AMI patients. EPVS is a predictor for predicting in-hospital mortality of AMI, and could help refine risk stratification.


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