Identification of a Three-Gene Signature Based on Epithelial-Mesenchymal Transition of Lung Adenocarcinoma Through Construction and Validation of a Risk-Prediction Model

Abstract

Epithelial-mesenchymal transition (EMT) process, which is regulated by genes of inducible factors and transcription factor family of signaling pathways, transforms epithelial cells into mesenchymal cells and is involved in tumor invasion and progression and increases tumor tolerance to clinical interventions. This study constructed a multigene marker for lung predicting the prognosis of lung adenocarcinoma (LUAD) patients by bioinformatic analysis based on EMT-related genes. Gene sets associated with EMT were downloaded from the EMT-gene database, and RNA-seq of LUAD and clinical information of patients were downloaded from the TCGA database. Differentially expressed genes were screened by difference analysis. Survival analysis was performed to identify genes associated with LUAD prognosis, and overlapping genes were taken for all the three. Prognosis-related genes were further determined by combining LASSO regression analysis for establishing a prediction signature, and the risk score equation for the prognostic model was established using multifactorial COX regression analysis to construct a survival prognostic model. The model accuracy was evaluated using subject working characteristic curves. According to the median value of risk score, samples were divided into a high-risk group and low-risk group to observe the correlation with the clinicopathological characteristics of patients. Combined with the results of one-way COX regression analysis, HGF, PTX3, and S100P were considered as independent predictors of LUAD prognosis. In lung cancer tissues, HGF and PTX3 expression was downregulated and S100P expression was upregulated. Kaplan-Meier, COX regression analysis showed that HGF, PTX3, and S100P were prognostic independent predictors of LUAD, and high expressions of all the three were all significantly associated with immune cell infiltration. The present study provided potential prognostic predictive biological markers for LUAD patients, and confirmed EMT as a key mechanism in LUAD progression.

Identification of PSMD11 as a novel cuproptosis‐ and immune‐related prognostic biomarker promoting lung adenocarcinoma progression

“… 33 Although controversy surrounds the prognostic biomarker role of HGF in different types of cancer, 34 some studies have shown that high expression of HGF predicts improved survival of patients with LUAD. 35 , 36 , 37 HLA‐DMA is a nonclassical MHC II molecule associated with antigen presentation in immune cells. HLA‐DMA catalyzes peptide exchange on classical MHC II molecules and protects empty MHC class II proteins from functional inactivation and disintegration.…”

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

“…With rapid advancements in high-throughput sequencing, abundant studies have used data from large communal databases, for example, TCGA and GEO databases, to construct the prognostic signatures for identification of patient risk stratification, guidance of treatment regimens, precise prognostic assessment, and improvement of clinical efficacy ( 68 , 69 ). Previous studies have reported risk-prediction models based on EMT in LUAD ( 37 , 38 ). Although the conventional analytical methods used were similar, the genes required for construction of the signatures were fundamentally different, mainly due to the different databases and screening processes.…”

“…In addition, compared with the previously reported EMT models, we conducted in vitro experiments in-depth to verify a dramatically correlation between our signature and EMT procedure. Collectively, the specific E-signature we developed could predict the cancer process more comprehensively and accurately, with more stable and robust predictive performance and superior clinical practice ( 37 , 38 ).…”

“…Nevertheless, the existence of heterogeneity in samples among diversified studies on various tumours resulting in different risk models (35). Recently, some researchers reported the prognostic significance of E-signature, however they did not validate the biological functions of EMT-related genes with in vitro experiments in LUAD and their studies remains rudimentary to some extent (36)(37)(38).…”

Screening and identifying a novel M-MDSCs-related gene signature for predicting prognostic risk and immunotherapeutic responses in patients with lung adenocarcinoma

“…Benefiting from the advancements in sequencing technologies and machine learning algorithms, understanding of the characteristics of TME at the molecular level has substantial clinical value to predict prognosis in patients. In the TME of LUAD, many studies have been focused on the prognosis of T cells ( Du et al, 2021 ), B cells ( Zhang et al, 2021 ), cancer-associated fibroblasts (CAFs) ( Navab et al, 2011 ; Min et al, 2021 ), and tumor-associated macrophages (TAMs) ( Chen et al, 2021 ), as well as the biological processes, including epithelial-mesenchymal transition (EMT) ( Shi et al, 2021 ) and angiogenesis ( Cai et al, 2021 ). However, the analysis on the prognostic significance of M-MDSCs, showing a strong immunosuppressive function, is still insufficient.…”