Abstract
Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.
Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression analysis were applied to identify IRGs and to construct a prognostic signature and nomogram.
Results: MiR-3648 was expectedly highly expressed in EA tumor tissues (P=2.6e-8), and related to the infiltration of activated natural killer cells (NK cells) and activated CD4 T lymphocytes (CD4 cells). A total of 70 miR-3648-targeted genes related to immune cell infiltration were identified. Among them, 4 genes (C10orf55, DLL4, PANX2, and NKAIN1) were closely related to overall survival (OS), and were thus selected to construct a 4-gene risk score (RS). The RS had a superior capability to predict OS [area under the curve (AUC) =0.740 for 1 year; AUC =0.717 for 3 years; AUC =0.622 for 5 years]. A higher score was indicative of a poorer prognosis than a lower score [hazard ratio (HR) =2.71; 95% confidence interval (CI): 1.45–5.09; P=0.002]. Furthermore, the nomogram formed by combining the RS and the TNM classification of malignant tumors (TNM stage) improved the accuracy of survival prediction [Harrell’s concordance index (C-index) =0.698].
Conclusions: MiR-3648 may play a critical role in EA pathogenesis. The novel 4-gene signature may serve as a prognostic tool to manage patients with EA.
Document Type
Article
Publication Date
11-2021
Digital Object Identifier (DOI)
https://doi.org/10.21037/atm-21-6237
Funding Information
This study was supported by the Project of Wu Jieping Medical Foundation (320.6750.19092.42).
Repository Citation
Zhang, Donglei; Yin, Hang; Bauer, Thomas L.; Rogers, Michael P.; Velotta, Jeffrey B.; Morgan, Clinton T.; Du, Weijia; Xu, Ping; and Qian, Xiaozhe, "Development of a Novel miR-3648-Related Gene Signature as a Prognostic Biomarker in Esophageal Adenocarcinoma" (2021). Surgery Faculty Publications. 50.
https://uknowledge.uky.edu/surgery_facpub/50
Notes/Citation Information
Published in Annals of Translational Medicine, v. 9, no. 22.
© Annals of Translational Medicine
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