Transcriptomic analysis and experimental verification reveal the multiple roles of angiogenesis factors in esophageal cancer

doi:10.4251/wjgo.124375

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Dec 15, 2026; 18(12): 124375
Published online Dec 15, 2026. doi: 10.4251/wjgo.124375

Transcriptomic analysis and experimental verification reveal the multiple roles of angiogenesis factors in esophageal cancer

Ling Xu, Da Li, Tian Xu, Kun Zhang, Jing-Yao Feng, Li-Jun Hu, Jian-Lin Wang

Ling Xu, Department of Radiotherapy, The Third Affiliated Hospital of Nanjing Medical University, The Second People’s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China

Da Li, Tian Xu, Kun Zhang, Jing-Yao Feng, Li-Jun Hu, Jian-Lin Wang, Department of Radiotherapy, The Third Affiliated Hospital of Nanjing Medical University, The Second People’s Hospital of Changzhou, Changzhou 213003, Jiangsu Province, China

Co-first authors: Ling Xu and Da Li.

Co-corresponding authors: Li-Jun Hu and Jian-Lin Wang.

Author contributions: Xu L and Li D contribute equally to this study as co-first authors; Xu L, Li D, Feng JY, Hu LJ, and Hu LJ contributed to conceptualization; Xu L, Li D, and Zhang K contributed to data curation, investigation, project administration, and software; Xu L, Li D, Xu T, Feng JY, and Wang JL contributed to formal analysis; Xu L and Li D contributed to methodology and resources; Xu L, Li D, and Xu T contributed to visualization; Xu L, Li D, Xu T, Zhang K, Feng JY, and Wang JL contributed to writing - original draft; Xu L, Li D, Hu LJ, and Wang JL contributed to writing - review and editing; Xu T and Feng JY contributed to validation; Xu T contributed to supervision; Wang JL contributed to funding acquisition; Hu LJ and Wang JL contributed equally as co-corresponding authors. All authors approved the final version to publish.

AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.

Supported by Top Talent of Changzhou “The 14^th Five-Year Plan” High-Level Health Talents Training Project, No. 2022CZBJ070; Science and Technology Project of Changzhou Health Commission, No. ZD202313; Clinical Program of Changzhou Medical Center, Nanjing Medical University, No. CMCC202401; Changzhou Sci&Tech Program, No. CJ20253095; and Changzhou University-Changzhou Second People’s Hospital Nursing Special Research Project, No. CDHL202503.

Institutional review board statement: The research protocol was approved by the Ethics Committee of the Second People’s Hospital of Changzhou, No. 2022-0223.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: No additional data are available.

Corresponding author: Jian-Lin Wang, Associate Chief Physician, Department of Radiotherapy, The Third Affiliated Hospital of Nanjing Medical University, The Second People’s Hospital of Changzhou, No. 468 Yanling Middle Road, Tianning District, Changzhou 213003, Jiangsu Province, China. wangjianlin@njmu.edu.cn

Received: June 15, 2026
Revised: July 13, 2026
Accepted: September 8, 2026
Published online: December 15, 2026
Processing time: 148 Days and 6.2 Hours

Abstract

BACKGROUND

For the poor prognosis of esophageal cancer (ESCA), the novel and effective prognostic biomarkers of ESCA remain to be imperative.

AIM

To develop a prognostic risk model for ESCA based on angiogenesis factors (AFs).

METHODS

Based on TCGA data, differential expression analysis was performed in ESCA. Differentially expressed prognosis-related AFs were screened using sequential criteria: Retrieval of 1054 angiogenesis-related genes from NCBI, identification of 250 differential expression AFs (|log₂(FC)| ≥ 1 and adjusted P value < 0.01), univariate Cox screening (P < 0.05), and least absolute shrinkage and selection operator regression model construction. The correlations between this model, immune infiltration, immune escape-related features, and potential clinical application were analyzed. Quantitative real-time polymerase chain reaction validated five candidate AFs, and in vitro small interfering RNA-mediated silencing of APLN was used for functional assessment.

RESULTS

Total 12 differential expression AFs associated with prognosis of ESCA were constructed the risk model. ESCA patients were assigned to high- and low-risk groups based on their risk scores. Patients in the low-risk group had a higher survival rate than those in the high-risk group. Risk scores were correlated with the cell stemness index. The contents of CD4+ T cells, neutrophils and macrophages differed between the high- and low-risk groups, accompanied by differences in stromal score and ESTIMATE tumor purity score. This model showed better survival-discrimination performance than TIDE score in this dataset, although the two scores reflect different biological dimensions. Multivariate Cox analysis supported the risk score as an independent prognostic factor. APLN knockdown markedly suppressed ESCA cell proliferation, angiogenic capability, and vascular endothelial growth factor expression/secretion, supporting a pro-tumor role of APLN in ESCA progression.

CONCLUSION

The AF-based model may serve as a promising prognostic variable for ESCA, pending further validation in larger independent cohorts. Combined with experimental validation, our findings support the involvement of APLN in ESCA progression and provide a preliminary framework for functionally classifying tumors and exploring individualized treatment strategies.

Keywords: Esophageal cancer; Angiogenesis factor; Prognostic risk model; Independent prognosis factor; APLN

Core Tip: This study highlights that angiogenesis factor-based model could be used as a promising variable for predicting the prognosis of esophageal cancer. When combined with experimental validation, our findings demonstrate the critical role of APLN in the development of esophageal cancer. They also offer a new theoretical and practical framework for classifying tumours functionally and developing personalized treatment strategies.