A novel epithelial-mesenchymal transition (EMT)-related gene signature of predictive value for the survival outcomes in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is a remarkably heterogeneous and aggressive disease with dismal prognosis of patients. The identification of promising prognostic biomarkers might enable effective diagnosis and treatment of LUAD. Aberrant activation of epithelial-mesenchymal transition (EMT) is required for LUAD initiation, progression and metastasis. With the purpose of identifying a robust EMT-related gene signature (E-signature) to monitor the survival outcomes of LUAD patients. In The Cancer Genome Atlas (TCGA) database, least absolute shrinkage and selection operator (LASSO) analysis and cox regression analysis were conducted to acquire prognostic and EMTrelated genes. A 4 EMT-related and prognostic gene signature, comprising dickkopf-like protein 1 (DKK1), lysyl oxidase-like 2 (LOXL2), matrix Gla protein (MGP) and slit guidance ligand 3 (SLIT3), was identified. By the usage of datum derived from TCGA database and Western blotting analysis, compared with adjacent tissue samples, DKK1 and LOXL2 protein expression in LUAD tissue samples were significantly higher, whereas the trend of MGP and SLIT3 expression were opposite. Concurrent with upregulation of epithelial markers and downregulation of mesenchymal markers, knockdown of DKK1 and LOXL2 impeded the migration and invasion of LUAD cells. Simultaneously, MGP and SLIT3 silencing promoted metastasis and induce EMT of LUAD cells. In the TCGA-LUAD set, receiver operating characteristic (ROC) analysis indicated that our risk model based on the identified E-signature was superior to those reported in literatures. Additionally, the E-signature carried robust prognostic significance. The validity of prediction in the E-signature was validated by the three independent datasets obtained from Gene Expression Omnibus (GEO) database. The probabilistic nomogram including the E-signature, pathological T stage and N stage was constructed and the nomogram demonstrated satisfactory discrimination and calibration. In LUAD patients, the E-signature risk score was associated with T stage, N stage, M stage and TNM stage. GSEA Frontiers in Oncology frontiersin.org 01

Identification of a Novel Prognostic Lymphangiogenesis‐Related Signature Associated with Tumor Immunity for Guiding Therapy in Lung Adenocarcinoma

“…The promotion of LUAD development is facilitated by LOXL2, which functions as a pivotal gene in both epithelial-mesenchymal transition and copper metabolism [36,37]. MKI67 is a significant factor in multiple molecular progression of LUAD [38,39].…”

LINC01117 inhibits invasion and migration of lung adenocarcinoma through influencing EMT process

“…EMT is a mechanism that was first discovered in the 1980s [ 19 ]. EMT is the transition of cells from an epithelial to a mesenchymal state [ 20 , 21 ]. This process modifies cell-expressed adhesion molecules, including E-cadherin, which is responsible for tight junctions, and the miRNA200 family, which helps maintain the epithelial phenotype.…”

Integrated single-cell RNA-seq analysis reveals mitochondrial calcium signaling as a modulator of endothelial-to-mesenchymal transition

“…Other genes were involved in protein trafficking and turnover (e.g., FBXW11, HERC1, RTN2, SEL1L, SNX27, and UBXN7), cytoskeletal remodeling (e.g., ARHGAP10, DCTN1, and TES), and metabolism (e.g., ALG8, ATP8A1, DEGS1, EPM2A, and SLC2A1), in line with the profile of (metabolically) active cells (table S6). Top-ranking genes identified by our rank product-based meta-analysis approach included all known canonical EndMT marker genes (e.g., ENG, SNAI1, SNAI2, TWIST1, VIM, S100A4, CDH2, TWIST2, SERPINE1, CD44, and ZEB2) (7), genes previously described to be broadly involved in mesenchymal activation/transition [SMURF1 and SMURF2 (21), BGN (22), TAGLN (23), CNN1 (23), ELN (24), MGP (25), AIFM2 (26), ATXN1 (27), ID1 (28), MMP14 (29), and NES (30)], and genes involved in extracellular matrix (ECM) remodeling (FN1, COL1A2, COL1A1, and COL3A1) and the TGF-β signaling pathway (TGFB1, TGFBR1, BMPR2, TGFB2, LTBP1, SMAD1, SMAD2, ACVRL1, TGFBR2, BMP2, and SMAD3) with an established role in EndMT (Fig. 3B and table S6) (7,31).…”