Retrospective Cohort Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Aug 27, 2025; 17(8): 106898
Published online Aug 27, 2025. doi: 10.4240/wjgs.v17.i8.106898
Effects of low-density lipoprotein cholesterol on lymph node metastasis after radical esophagectomy
Xin-Jian Xu, Shi-Wei Liu, Jia-Qi Li, Ming He, Hui Wang, Qing-Ju Meng
Xin-Jian Xu, Postdoctoral Research Station of Hebei Medical University, Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Shi-Wei Liu, Qing-Ju Meng, Department of Oncology, The First Affiliated Hospital of Xingtai Medical College, Xingtai 054001, Hebei Province, China
Jia-Qi Li, Clinical College of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Ming He, Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Hui Wang, Department of Traditional Chinese Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Author contributions: Xu XJ and Meng designed the research study; Liu SW, Li JQ, He M, and Wang H performed the research; and Xu XJ, Liu SW, and Li JQ collected and analyzed the data; Xu XJ, He M, and Wang H were involved in drafting the manuscript, and all authors were involved in revising it critically for important intellectual content. All authors provided final approval for the version to be published. All authors participated sufficiently in the work to take public responsibility for appropriate portions of the content and agreed to be accountable for all aspects of the work to ensure that questions are related to its accuracy or integrity.
Institutional review board statement: The study was reviewed and approved for publication by the First Affiliated Hospital of Xingtai Medical College.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at ehyd-xxj@163.com. Participants gave informed consent for data sharing.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qing-Ju Meng, MD, Department of Oncology, The First Affiliated Hospital of Xingtai Medical College, No. 376 Shunde Road, Xingtai 054001, Hebei Province, China. hyd-xxj@163.com
Received: May 14, 2025
Revised: June 5, 2025
Accepted: July 11, 2025
Published online: August 27, 2025
Processing time: 103 Days and 4 Hours
Abstract
BACKGROUND

Esophageal cancer (EC) is one of the most common malignancies worldwide, and lymph node (LN) metastasis remains one of the leading causes of EC recurrence. Metabolic disorders critically affect cancer progression, and lipid levels are closely associated with the occurrence of EC and several other tumor types. This study analyzed pretreatment lipid levels to determine their association with LN metastasis.

AIM

To dissect the possible mechanisms underlying LN metastasis and clarify the prognostic role of lipid profiles in EC.

METHODS

Serum lipid levels and clinicopathological information were retrospectively collected from 294 patients, and risk factors for LN metastasis were confirmed using a logistic regression model. Latent factors were explored using information from publicly accessible databases and immunofluorescence and immunohistochemical staining techniques.

RESULTS

High serum levels of low-density lipoprotein (LDL) cholesterol promote LN metastasis in EC, while high-density lipoprotein cholesterol has the opposite role. Information of a public database revealed that LDL receptors LRP5 and LRP6 are highly expressed in ECs, and LRP6 overexpression positively correlated with the infiltration of B lymphocytes and a poor prognosis. Immunofluorescence and immunohistochemical staining revealed that the expression of LRP6 and infiltrated B lymphocytes in patients with ≥ 1 regional LN metastasis, containing N1-3 (N+ group) were significantly higher than those in the N0 group. LRP6 was also highly expressed in the B lymphocytes of the N+ group. There was no difference in CXCL13 expression between the N+ and N0 groups. However, CXCR5 expression was significantly higher in the N0 group than in the N+ group.

CONCLUSION

High serum LDL levels can promote LN metastasis in EC, and the mechanisms may be related to LRP6 expression and the infiltration of B lymphocytes.

Keywords: Esophageal cancer; Lymph node metastasis; Low-density lipoprotein cholesterol; B lymphocytes

Core Tip: This study investigated the relationship between pretreatment serum levels of low-density lipoprotein cholesterol (LDL-c) and lymph node (LN) metastasis in patients with esophageal cancer (EC) undergoing radical esophagectomy. Analysis of data from 294 patients revealed that elevated LDL-c levels significantly promoted LN metastasis, in contrast to the protective role of high-density lipoprotein. Further exploration using public databases and immunohistochemical techniques identified LRP5/6, particularly LRP6, as highly expressed in EC tissues, with LRP6 overexpression correlating with increased B-lymphocyte infiltration and adverse prognosis. Notably, patients with regional LN metastasis (N+ group) exhibited significantly higher expression of LRP6 and infiltrated B lymphocytes than those without regional LN metastasis (N0 group). Although CXCL13 expression remained comparable between the groups, CXCR5 expression was notably higher in the N0 group. These findings suggest that high serum LDL-c levels facilitate LN metastasis in EC, potentially through mechanisms involving LRP6 expression and B lymphocyte infiltration, thereby offering novel insights into the prognostic role of lipid profiles in EC progression.