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

Abstract

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.

Identification of Novel Prognostic Markers Associated With Laryngeal Squamous Cell Carcinoma Using Comprehensive Analysis

“…Moreover, the increased deposition of ECM proteins is one of the main reasons for this. The ECM is a fundamental and important component of all tissue organs; it also interacts with tumor cells and regulates tumor growth, proliferation, differentiation, adhesion, and metastasis (42)(43)(44). Here, we confirmed that most of the core ECM genes, such as collagens, proteoglycans, and glycoproteins, were highly expressed in the LSCC tissues than in the adjacent normal mucosal tissues (Supplementary Figure 2).…”

Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells

“…In order to understand the SA-induced migratory modulation, we evaluated the effects of SA treatment over genes related to cell migration and extracellular matrix. Since the baseline expression signature of both cell lines is different, up and down-regulated genes differ between both cell lines [45][46][47], highlighting the relevance of the genetic background of the cell. For instance, we could not detect expression of TIMP3 and IL-6 in H1299 cells, while both genes presented SA-altered expression in the A549 cell line.…”

Macrophage-Related SPP1 as a Potential Biomarker for Early Lymph Node Metastasis in Lung Adenocarcinoma

“…Secreted phosphoprotein 1 (SPP1), a hallmark gene of the EMT process, can participate in extracellular matrix (ECM)-receptor interactions and the focal adhesion response pathway to regulate tumor metastasis and invasion. SPP1 is significantly associated with adverse survival outcomes in various cancers ( Wei et al, 2020 ; He et al, 2021 ; Wang et al, 2021 ). Notably, higher SPP1 expression levels are related to a higher N stage in LUAD patients ( Guo et al, 2020 ), although the underlying mechanism has not yet been studied fully.…”