Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan.
Department of Teaching and Research, Taipei City Hospital, Taipei, Taiwan; Commission for General Education, National United University, Miaoli, Taiwan; General Education Center, University of Taipei, Taipei, Taiwan.
Transl Res. 2024 Jan;263:1-14. doi: 10.1016/j.trsl.2023.07.011. Epub 2023 Aug 8.
Early prognosis of cancer recurrence remains difficult partially due to insufficient and ineffective screening biomarkers or regimes. This study evaluated the rare circulating tumor microemboli (CTM) from liquid biopsy individually and together with circulating tumor cells (CTCs) and serum CEA/CA19-9 in a panel, on early prediction of colorectal cancer (CRC) recurrence. Stained CTCs/CTM were detected by a microfluidic chip-based automatic rare-cell imaging platform. ROC, AUC, Kaplan-Meier survival, and Cox proportional hazard models regarding 4 selected biomarkers were analyzed. The relative risk, odds ratio, predictive accuracy, and positive/negative predictive value of biomarkers individually and in combination, to predict CRC recurrence were assessed and preliminarily validated. The EpCAMHochestCD45 CTCs/CTM could be found in all cancer stages, where more recurrences were observed in late-stage cases. Significant correlations between CTCs/CTM with metastatic stages and clinical treatment were illustrated. CA19-9 and CTM could be seen as independent risk factors in patient survivals, while stratified patients by grouped biomarkers on the Kaplan-Meier analyses presented more significant differences in predicting CRC recurrences. By monitoring the panel of selected biomarkers, disease progressions of 4 CRC patients during follow-up visits after first treatments within 3 years were predicted successfully. This study unveiled the value of rare CTM on clinical studies and a panel of selected biomarkers on predicting CRC recurrences in patients at the early time after medical treatment, in which the CTM and serum CA19-9 could be applied in clinical surveillance and CRC management to improve the accuracy.
早期癌症复发的预测仍然具有一定难度,部分原因是缺乏有效的筛选生物标志物或方案。本研究评估了液体活检中罕见的循环肿瘤微栓子(CTM)与循环肿瘤细胞(CTC)和血清 CEA/CA19-9 联合检测在结直肠癌(CRC)早期复发预测中的作用。通过基于微流控芯片的自动稀有细胞成像平台检测染色的 CTC/CTM。对 4 种选定的生物标志物进行 ROC、AUC、Kaplan-Meier 生存和 Cox 比例风险模型分析。评估并初步验证了生物标志物单独和联合预测 CRC 复发的相对风险、优势比、预测准确性和阳性/阴性预测值。EpCAMHochestCD45 CTC/CTM 可在所有癌症分期中发现,晚期病例中观察到更多的复发。CTM 与转移性分期和临床治疗之间存在显著相关性。CA19-9 和 CTM 可作为患者生存的独立危险因素,而在 Kaplan-Meier 分析中对分组生物标志物分层的患者在预测 CRC 复发方面表现出更显著的差异。通过监测选定生物标志物的联合检测,可成功预测 4 例 CRC 患者在治疗后 3 年内首次治疗后随访期间的疾病进展情况。本研究揭示了 CTM 在临床研究中的价值以及一组选定的生物标志物在预测治疗后早期 CRC 复发中的价值,其中 CTM 和血清 CA19-9 可应用于临床监测和 CRC 管理,以提高准确性。