Identification and Validation of MYADM as a Novel Prognostic Marker Related to EMT in ESCC

TL;DR

This study identifies MYADM as a new marker linked to cancer progression and drug resistance in esophageal cancer.

Contribution

MYADM is newly identified as a prognostic marker related to EMT in ESCC, with experimental validation of its role in cancer progression and paclitaxel resistance.

Findings

MYADM is significantly upregulated in ESCC and correlates with poor clinical outcomes.

MYADM promotes cell proliferation, migration, and EMT, contributing to cancer progression and drug resistance.

MYADM's role in epithelial to mesenchymal transition supports its potential as a therapeutic target.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC), one of the most aggressive gastrointestinal malignancies, remains an enormous challenge in terms of medical treatment and prognostic improvement. Based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases in R language, the myeloid-associated differentiation marker (MYADM) was confirmed using bioinformatics analysis and experimental verification. MYADM is upregulated in multiple cancer types; however, the oncogenic mechanism by which MYADM promotes ESCC remains largely unknown.

Methods: In the present study, we used weighted gene coexpression network analysis to filter four hub genes (AKAP12, ITGA1, JAM2, and MYADM) in GSE45670 and GSE23400 that are related to the malignant progression of ESCC. Transcription factors and target miRNAs of the hub genes were predicted using the TarBase and JASPRAR databases, respectively, and a regulatory network was established. MYADM was selected based on the analysis of expression differences and prognostic value in ESCC. Next, we confirmed the level of MYADM in ESCC samples using immunohistochemistry of the tissue microarray. The molecular mechanisms of MYADM were further elucidated by experimental analyses, including Transwell assays, wound healing assays, and CCK8.

Results: The correlation between MYADM levels and the clinical data of patients with ESCC was confirmed, including tumor differentiation, the node and metastasis stage, T stage, lymphatic metastasis, and postoperative distant metastasis. MYADM was significantly upregulated in ESCC and positively correlated with overall survival. MYADM induced cell proliferation, migration, invasion, and wound healing via the epithelial to mesenchymal transition (EMT) pathway in multiple experiments. Moreover, our results supported the hypothesis that MYADM promotes EMT during paclitaxel resistance.

Conclusion: MYADM is closely correlated with ESCC progression, metastasis, and paclitaxel resistance and could be regarded as a novel biomarker and therapeutic target for ESCC patients.

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