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<p>Esophageal carcinoma (ESCA) is a highly aggressive malignancy with a 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.&#xa0;We integrated transcriptomic data from the TCGA and GEO databases with CRISPR screening to identify key oncogenes in ESCA. ALPN was identified as a key gene. Functional assays both in vitro and in vivo were conducted to explore the biological role of APLN. Mechanistic studies explored the involvement of APLN in the regulation of autophagy and chemoresistance. Furthermore, we developed an exosome-based siRNA delivery system targeting APLN and constructed a prognostic nomogram incorporating APLN expression.&#xa0;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 increased 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 causing systemic toxicity. Additionally, a nomogram combining APLN expression with clinical stage accurately predicts patient survival, providing a practical tool for individualized prognosis.&#xa0;Our study identified APLN as a novel driver of ESCA progression and chemoresistance through the regulation of autophagy. Targeting APLN via exosome-based siRNA delivery is a promising therapeutic strategy. Moreover, the APLN-based prognostic nomogram has potential for guiding personalized treatment decisions in ESCA patients.</p>

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

  • 期刊论文

  • 发表日期：

    2026年1月7日

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  • Weifeng Xu,
  • Caiyun Nie,
  • Chunbaixue Yang,
  • Zhen Liu,
  • Guanghui Liang,
  • Penghui Yu,
  • Huifang Lv,
  • Beibei Chen,
  • Jianzheng Wang,
  • Saiqi Wang,
  • Jing Zhao,
  • Yunduan He,
  • Shegan Gao,
  • Xiaobing Chen

摘要

Esophageal carcinoma (ESCA) is a highly aggressive malignancy with a 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. We integrated transcriptomic data from the TCGA and GEO databases with CRISPR screening to identify key oncogenes in ESCA. ALPN was identified as a key gene. Functional assays both in vitro and in vivo were conducted to explore the biological role of APLN. Mechanistic studies explored the involvement of APLN in the regulation of autophagy and chemoresistance. Furthermore, we developed an exosome-based siRNA delivery system targeting APLN and constructed a prognostic nomogram incorporating APLN expression. 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 increased 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 causing systemic toxicity. Additionally, a nomogram combining APLN expression with clinical stage accurately predicts patient survival, providing a practical tool for individualized prognosis. Our study identified APLN as a novel driver of ESCA progression and chemoresistance through the regulation of autophagy. Targeting APLN via exosome-based siRNA delivery is a promising therapeutic strategy. Moreover, the APLN-based prognostic nomogram has potential for guiding personalized treatment decisions in ESCA patients.