Prognostic value and therapeutic efficacy of interstitial circulating tumor cells in patients with advanced gastric cancer.

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.