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Retrospective Study
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World J Stem Cells. Jul 26, 2026; 18(7): 119714
Published online Jul 26, 2026. doi: 10.4252/wjsc.119714
Clinical significance of mesenchymal stem cells exosomal microRNAs in predicting prognosis and inflammatory response of esophageal cancer
Jin-Lin Wang, Ya-Xuan Niu, Han-Xiao Li, Fa-Cai Cui, Xiao Chen
Jin-Lin Wang, Ya-Xuan Niu, Han-Xiao Li, Fa-Cai Cui, Xiao Chen, Clinical Laboratory, Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
Author contributions: Wang JL conducted the majority of experiments and wrote the manuscript; Niu YX designed the study and served as a scientific advisor and guarantor; Li HX corrected the manuscript; Cui FC was involved in applying the analytical tools; Chen X participated in the collection of human material.
AI contribution statement: The authors confirm that no generative AI or AI-assisted technologies were used in the preparation of this manuscript.
Institutional review board statement: This study was approved by Henan Provincial People’s Hospital (Approval No. 2022-08), and the study followed the ethical guidelines of the Declaration of Helsinki.
Informed consent statement: Informed consent was obtained from all study participants.
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: Fa-Cai Cui, Chief Physician, Clinical Laboratory, Henan Provincial People’s Hospital, No. 7 Weiwu Road, Zhengzhou 450003, Henan Province, China. cuifacai1985@zzu.edu.cn
Received: February 27, 2026
Revised: March 19, 2026
Accepted: May 19, 2026
Published online: July 26, 2026
Processing time: 145 Days and 10.4 Hours
Abstract
BACKGROUND

Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer, accounting for over 90% of cases in Asia. Although the traditional tumor-node-metastases staging can to some extent assess prognosis, the biological heterogeneity leads to significant differences in survival among patients with the same stage.

AIM

To elucidate the relationship between two mesenchymal stem cells (MSCs) exosomal microRNAs (miRNAs) and ESCC.

METHODS

A total of 312 patients who underwent radical resection for ESCC were recruited. Preoperative blood samples were collected, and stem cells were isolated using the automatic blood cell separator. MSCs were further sorted by flow cytometry, and exosome was isolated using kit. The morphologies and particle sizes of exosomes were evaluated. The relative expression of miR-375/miR-655 in peripheral blood MSCs (PBMSCs) exosomes were assessed by quantitative real-time polymerase chain reaction. Associations with clinicopathological variables were assessed using the χ2 test or Fisher’s exact test, and Spearman’s rank correlation was employed to analyze the relationship between miR-375/miR-655 and inflammatory factors. Kaplan-Meier curves and log-rank tests assessed overall survival, and Cox models performed univariate/multivariate analyses on overall survival impact. Receiver operator characteristic curves evaluated the predictive performance of miR-375.

RESULTS

miR-375 and miR-655 showed elevated expression in PBMSC-derived exosomes from patients, in contrast to PBMSCs, and were associated with a lower incidence of poorly differentiated tumors, advanced tumor-node-metastases stages, and lymph node metastasis. The miR-375/miR-655 low expression group exhibited significantly elevated levels of interleukin (IL)-6, IL-1β, CC-chemokine ligand 2 (CCL2), and CCL5 compared to the high expression group. Spearman correlation analysis indicated a negative correlation between miR-375/miR-655 and IL-6, IL-1β, CCL2, and CCL5. Patients exhibiting high miR-375/miR-655 expression alongside low IL-6/IL-1β/CCL2/CCL5 expression demonstrated significantly longer overall survival compared to those with the opposite expression profiles. Multivariate Cox analysis determined miR-375 as an independent predictor of overall survival with notable accuracy.

CONCLUSION

Overexpression of miR-375 and miR-655 in PBMSCs exosomes derived from patients is associated with inflammatory factors and unfavorable prognosis in ESCC. Their combined evaluation provides improved prognostic stratification and may serve as a valuable adjunct for individualized clinical management.

Keywords: Esophageal squamous cell carcinoma; miR-375; miR-655; Inflammatory factors; Prognosis; Mesenchymal stem cells; Exosome

Core Tip: Overexpression of miR-375 and miR-655 in peripheral blood mesenchymal stem cells exosomes derived from patients is associated with inflammatory factors and unfavorable prognosis in esophageal squamous cell carcinoma. Their combined evaluation provides improved prognostic stratification and may serve as a valuable adjunct for individualized clinical management. The findings aim to provide new evidence for the biological and clinical relevance of these biomarkers and offer a reference for personalized prognosis assessment and clinical decision-making in esophageal squamous cell carcinoma management.

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