Department of Surgical Oncology, Xi'an Jiaotong University Medical College First Affiliated Hospital, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
Department of Pathology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Sci Rep. 2024 Jun 4;14(1):12758. doi: 10.1038/s41598-024-63305-3.
Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101-0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169-8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071-0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28-80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.
循环肿瘤细胞（CTC）作为一种液体活检在临床应用和基础癌症研究中具有巨大潜力，但在胃癌中的临床应用仍不清楚。本研究旨在探讨 CTC 是否可作为胃癌患者潜在的预后预测指标。
纳入了 2015 年 1 月 1 日至 2019 年 12 月 1 日期间经病理证实的 120 例胃癌患者。所有患者均在未接受先前治疗的情况下初步诊断，然后在根治性手术切除前使用 NEimFISH 方法检测 CTC 数量。对所有患者进行定期随访，并评估 CTC 数量与无病生存期（DFS）和总生存期（OS）等临床终点的相关性。使用 Cox 比例风险模型计算单变量和多变量风险比。根据 CTC 数量，我们将每 7.5 ml 全血中 CTC 数量≥2 定义为阳性组，将 CTC 数量<2 定义为阴性组。在接受手术前 CTC 检测的 120 例患者中，CTC 阳性患者的比例为 64.17%（77/120），其中Ⅰ期和Ⅱ期患者占 22.50%，Ⅲ期患者占 41.67%（P=0.014）。通过检测手术前和复发时的 CTC，其数量往往随着疾病进展而同步增加（中位数：2 对 7.5 ml 时为 5 个）。多变量分析显示，年龄（HR，0.259；95%CI，0.101-0.662；P=0.005）、D-二聚体（HR，3.146；95%CI，1.169-8.461；P=0.023）和淋巴结转移（HR，0.207；95%CI，0.0071-0.603；P=0.004）是与 CTC 相关的因素。此外，所有患者的中位随访时间为 38.0 个月（28-80 个月）；CTC 阳性患者的 DFS 明显短于 CTC 阴性患者，Cox 比例风险回归模型分析显示差异有统计学意义（44.52±2.83 m 比 74.99±2.78 m，HR=4.550，P=0.018）。在手术前，CTC 阳性组的 OS 短于 CTC 阴性组，但 Cox 比例风险回归模型分析结果无统计学意义（47.58±2.46 m 比 70.68±3.53 m，HR=2.261，P=0.083）。
CTC 数量往往随着疾病进展而同步增加。此外，CTC 的检测是胃癌患者 DFS 较短的独立预测指标。然而，CTC 与 OS 的关系需要在未来的研究中确定。
