Analysis of Expression and Its Clinical Significance of the Secreted Phosphoprotein 1 in Lung Adenocarcinoma

Guo, Zixin; Huang, Jingyu; Wang, Yujin; Li, Xiaoping; Li, Wei; Yao, Jie; Sheng, Li; Hu, Weidong

doi:10.3389/fgene.2020.00547

Cited by 21 publications

(19 citation statements)

References 62 publications

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“…More evidence shows that SPP1 was overexpressed in various types of cancers and contributes to the occurrence and development of tumors, including colorectal cancer, cervical cancer, gastric cancer, and so on (27)(28)(29)(30). The result of our finding that SPP1 may be a potential biomarker for lung adenocarcinoma was consistent with several studies (31,32). More reports had illustrated the relationship between the expression level of SPP1 and lung adenocarcinoma.…”

Section: Compared With Normal Tissues Only the Spp1 Expressionsupporting

confidence: 90%

Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis

Liu

Yang

et al. 2021

Front. Oncol.

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Lung adenocarcinoma (LUAD) is one of the most malignant tumors with high morbidity and mortality worldwide due to the lack of reliable methods for early diagnosis and effective treatment. It’s imperative to study the mechanism of its development and explore new biomarkers for early detection of LUAD. In this study, the Gene Expression Omnibus (GEO) dataset GSE43458 and The Cancer Genome Atlas (TCGA) were used to explore the differential co-expressed genes between LUAD and normal samples. Three hundred sixity-six co-expressed genes were identified by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) method. Those genes were mainly enriched in ameboidal-type cell migration (biological process), collagen-containing extracellular matrix (cell component), and extracellular matrix structure constituent (molecular function). The protein-protein network (PPI) was constructed and 10 hub genes were identified, including IL6, VWF, CDH5, PECAM1, EDN1, BDNF, CAV1, SPP1, TEK, and SELE. The expression level of hub genes was validated in the GEPIA database, compared with normal tissues, VWF is lowly expressed and SPP1 is upregulated in LUAD tissues. The survival analysis showed increased expression of SPP1 indicated unfavorable prognosis whereas high expression of VWF suggested favorable prognosis in LUAD (p < 0.05). Based on the immune infiltration analysis, the relationship between SPP1 and VWF expression and macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD. Quantitative real-time PCR (qRT-PCR) and western blotting were used to validate the expression of VWF and SPP1 in normal human bronchial epithelial (HBE) cell and three LUAD cell lines, H1299, H1975, and A549. Immunohistochemistry (IHC) was further performed to detect the expression of VWF in 10 cases LUAD samples and matched normal tissues. In summary, the data suggest that VWF is a potential novel biomarker for prognosis of LUAD.

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Section: Compared With Normal Tissues Only the Spp1 Expressionsupporting

confidence: 90%

Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis

Liu

Yang

et al. 2021

Front. Oncol.

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“…Specifically, miR-539-5p emerged with the highest node degrees compared to other nodes in the network. Several studies found that miR-539-5p expression levels associated with a poor prognosis and negatively correlated with hypoxia and the stem index among LUAD patients ( González-Vallinas et al, 2018 ; Guo et al, 2020 ). Yet, further experiments are needed to verify these results given the limited evidence documenting the direct mechanisms of miR-539-5p in LUAD.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis

Wang

Gao

Wang

et al. 2021

Front. Cell Dev. Biol.

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BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA–mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein–protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA–mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA–mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.

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“…The up-regulated SPP1, COL1A1, and COL3A1 in LUAD were positively correlated with each other, while the down-regulated PECAM1, VWF, EDN1, CDH5, and TEK were in LUAD also positively correlated with each other. Guo et al studied the expression and clinical significance of SPP1 in LUAD and found that SPP1 influenced the initiation and progression of LUAD, which was considered as a new target for molecular treatment [ 13 ]. Similarly, we tried to determine the mechanisms of PECAM1 in LUAD.…”

Section: Discussionmentioning

confidence: 99%

Key microRNAs and hub genes associated with poor prognosis in lung adenocarcinoma

Liu

Huang

et al. 2021

Aging

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In the study, we obtained 36 pairs of lung adenocarcinoma (LUAD) tissues and adjacent non-tumorous tissues. Then, we chose a specific hub-target gene of miRNA and used qRT-PCR to evaluate the expression of PECAM1. We found that the expression level of PECAM1 mRNA in LUAD was significantly lower than that in adjacent nontumor tissues (P<0.0001). Univariate and multivariate analyses were conducted on 481 LUAD patients from The Cancer Genome Atlas (TCGA) according to the Cox proportional hazard regression model to evaluate the impact of PECAM1 expression and other clinicopathological factors on survival. The results showed that the low expression of PECAM1 was an important independent predictor of poor overall survival (HR, 0.704; 95% CI, 0.518-0.957; P = 0.025). Based on the Tumor Immune Estimation Resource (TIMER) database, the relationship between PECAM1 expression and B cell, CD8+ T cell, CD4+ T cell, macrophage, neutrophil, and dendritic cell infiltration was weak in LUAD (P<0.01). In particular, a more significant positive correlation between PECAM1 expression and HLA-complex members, CD1C, NRP1, and ITGAX expression in dendritic cell was detected in LUAD. The mechanism which PECAM1 involved in the development of LUAD may be closely related to changes in the immune microenvironment.

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Analysis of Expression and Its Clinical Significance of the Secreted Phosphoprotein 1 in Lung Adenocarcinoma

Abstract: Objective: To explore the expression of secreted phosphoprotein 1 (SPP1) in lung adenocarcinoma (LUAD), and evaluate its relationship with clinicopathological characteristics and prognosis of LUAD, and analyze the advantages of SPP1 as a potential prognostic marker in LUAD.

Cited by 21 publications

References 62 publications

Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis

Identification of VWF as a Novel Biomarker in Lung Adenocarcinoma by Comprehensive Analysis

Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis

Key microRNAs and hub genes associated with poor prognosis in lung adenocarcinoma

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