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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Prognostic value and therapeutic efficacy of interstitial circulating tumor cells in patients with advanced gastric cancer
Jing Yang, Zu-Xi Li, Mei-Juan Song, Shang-Jun Han, Ai-Jia Yang, Ze-Ping Zhang, Chang-Sheng Sui, Ji-Lin Qiao, Wen-Hua Huang, Jun-Qiang He
Jing Yang, Wen-Hua Huang, Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, Guangdong Province, China
Jing Yang, Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
Jing Yang, Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
Zu-Xi Li, Department of Peripheral Vascular Intervention, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730060, Gansu Province, China
Mei-Juan Song, Shang-Jun Han, Ai-Jia Yang, Ze-Ping Zhang, Chang-Sheng Sui, Ji-Lin Qiao, The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
Jun-Qiang He, Department of General Surgery, Xinhui People’s Hospital of Southern Medical University, Jiangmen 529000, Guangdong Province, China
Co-first authors: Jing Yang and Zu-Xi Li.
Co-corresponding authors: Wen-Hua Huang and Jun-Qiang He.
Author contributions: Yang J and Li ZX contributed to study design, and contributed equally as co-first authors; Li ZX contributed to data analysis and manuscript preparation; Song MJ and Han SJ contributed to data acquisition and analysis; Yang AJ, Zhang ZP, and Sui CS contributed to data visualization and design enhancement; Qiao JL contributed to academic literature research; Huang WH and He JQ contributed to manuscript evaluation and supervision, and contributed equally as co-corresponding authors; and all authors contributed to the article and approved the submitted version.
Supported by China Postdoctoral Science Foundation, No. 2024M751334.
Institutional review board statement: This study was approved by the Ethics Committee of Gansu Provincial People’s Hospital (No.2020-208).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: sharing statement: All authors agree that all data related to this study will be publicly available.
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: Wen-Hua Huang, PhD, Professor, Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, No. 1023 Shatai North Road, Guang
zhou 510000, Guangdong Province, China.
huangwenhua2009@139.com
Received: September 25, 2024
Revised: March 8, 2025
Accepted: April 8, 2025
Published online: May 24, 2025
Processing time: 236 Days and 7.6 Hours
BACKGROUND
The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer (GC) patients. To optimize treatment stratification and management, there is an urgent need for efficient and non-invasive biomarkers. A meta-analysis on the prognostic role of circulating tumor cells (CTCs) in GC revealed a strong association between CTCs and patient prognosis. Among CTC subtypes, Interstitial CTCs (I-CTCs) exhibited the strongest invasiveness. This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.
AIM
To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC. To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients. To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.
METHODS
This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020. The expression levels of I-CTCs were measured, and patient survival was monitored. The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels. Based on this cut-off value, 59 GC patients were grouped into positive and negative groups. The differences in clinicopathological characteristics between the two groups were analyzed. Patient survival was follow-up and recorded until October 2022. Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors. The Kaplan-Meier method and Cox regression model were used, respectively.
RESULTS
A total of 59 patients were included in this study, and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5, with an area under the curve of 0.8356 (95%CI: 0.7122-0.9590). The I-CTC count of ≥ 5 defines the positive group, while counts < 5 are classified as the negative group. Positive I-CTCs correlated with the degree of tumor differentiation and disease progression (P < 0.05). 16 of 59 patients received neoadjuvant chemotherapy. There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy. Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group (P < 0.05). Multifactorial analysis revealed that I-CTCs positivity (HR = 13.323, 95%CI: 1.675-105.962, P = 0.014) was an independent risk factor for survival in patients with advanced GC.
CONCLUSION
In patients with advanced GC, an I-CTC count of ≥ 5 is associated with both poor prognosis and reduced chemotherapy efficacy. I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.
Core Tip: This study builds upon prior evidence-based research to innovatively assess the expression of interstitial circulating tumor cell (I-CTCs) in patients with advanced gastric cancer, demonstrating that I-CTCs can serve as valid indicators for evaluating chemotherapy efficacy and prognosis in this patient population. In patients with advanced gastric cancer, I-CTC count of ≥ 5 is associated with poor prognosis and reduced chemotherapy efficacy.
