APLN, a novel prognostic biomarker, contributes to esophageal carcinoma development

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

Background: Esophageal carcinoma (ESCA) is a highly aggressive malignancy with poor prognosis. The apelin gene (APLN) encodes a secreted peptide involved in various physiological processes, but its role in ESCA progression and chemoresistance remains unclear. Methods: We integrated transcriptomic data from TCGA and GEO databases with CRISPR screening to identify key oncogenes in ESCA. ALPN was identified as a key gene. Functional assays in vitro and in vivo were performed to investigate the biological role of APLN. Mechanistic studies explored the involvement of APLN in autophagy regulation and chemoresistance. Furthermore, we developed an exosome-based siRNA delivery system targeting APLN and constructed a prognostic nomogram incorporating APLN expression. Results: APLN was significantly overexpressed in ESCA tissues and correlated with poor patient prognosis. DNA hypomethylation contributed to APLN upregulation. Functional experiments demonstrated that APLN knockdown suppressed tumor cell proliferation, induced apoptosis, and enhanced sensitivity to cisplatin. Mechanistically, APLN promoted autophagic flux, which mediated chemoresistance in ESCA cells. Exosome-mediated delivery of APLN siRNA effectively inhibited tumor growth in vivo without systemic toxicity. Additionally, a nomogram combining APLN expression with clinical stage accurately predicted patient survival, providing a practical tool for individualized prognosis. Conclusions: Our study identifies APLN as a novel driver of ESCA progression and chemoresistance through autophagy regulation. Targeting APLN via exosome-based siRNA delivery offers a promising therapeutic strategy. Moreover, the APLN-based prognostic nomogram holds potential for guiding personalized treatment decisions in ESCA patients.

Article activity feed