Alsayed Aya, Salem Salem E, El Serafi Mostafa M, Abdellateif Mona S, Zekri Abdel-Rahman N, Mohanad Marwa, Bahnassy Abeer A
Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
Onco Targets Ther. 2021 Mar 16;14:1937-1951. doi: 10.2147/OTT.S292551. eCollection 2021.
Microsatellite instability (MSI) and circulating tumor cells (CTCs) play important roles in the diagnosis, prognosis and management of colorectal cancer (CRC) patients.
CTCs and MSI were assessed in the blood and representative tumor tissues of 100 CRC patients by flow cytometry (FCM) and PCR amplification. The data were correlated to relevant clinicopathological features of the patients, progression-free survival (PFS) and overall survival (OS) rates.
MSI-high was detected in 44 (44.0%) patients, MSI-low in 37 (37%), and microsatellite stable (MSS) in 19 (19.0%) patients (P=0.007). The baseline CTCs count (<4 cells/7mL blood) was reported in 39% of the patients, and CTCs ≥4 cells/7mL blood in 61% of the patients (P=0.028). Improved PFS and OS rates were associated significantly with MSI-high (P<0.001), decreased CTC levels during the course of treatment (P<0.001) and post-treatment CTCs (P=0.008). There was no significant association between MSI-high and PFS or OS in early-stage patients (P=0.187 and P=0.187; respectively); however, it was associated significantly with better PFS and OS in late-stage patients (P<0.001). Multivariate analysis showed that only a change in serial CTC levels is considered an independent prognostic factor for OS (P<0.012). Post-treatment CTCs level, serial CTCs level changes during the course of treatment, lymph nodes and distant metastasis were independent prognostic factors for PFS (P<0.001, P= 0.047, P=0.001 and P<0.001; respectively).
MSI and CTCs could be used as accurate, reliable and sensitive diagnostic and prognostic biomarkers for CRC patients' survival rates and outcomes.
微卫星不稳定性（MSI）和循环肿瘤细胞（CTCs）在结直肠癌（CRC）患者的诊断、预后及治疗中发挥着重要作用。
采用流式细胞术（FCM）和聚合酶链反应（PCR）扩增对100例CRC患者的血液及代表性肿瘤组织中的CTCs和MSI进行评估。将数据与患者的相关临床病理特征、无进展生存期（PFS）和总生存期（OS）率进行关联分析。
44例（44.0%）患者检测到MSI高，37例（37%）患者检测到MSI低，19例（19.0%）患者检测到微卫星稳定（MSS）（P = 0.007）。39%的患者基线CTCs计数（<4个细胞/7mL血液），61%的患者CTCs≥4个细胞/7mL血液（P = 0.028）。PFS和OS率的改善与MSI高显著相关（P<0.001），与治疗过程中CTCs水平降低（P<0.001）及治疗后CTCs相关（P = 0.008）。早期患者中MSI高与PFS或OS之间无显著关联（分别为P = 0.187和P = 0.187）；然而，在晚期患者中其与更好的PFS和OS显著相关（P<0.001）。多因素分析显示，仅连续CTCs水平的变化被视为OS的独立预后因素（P<0.012）。治疗后CTCs水平、治疗过程中连续CTCs水平变化、淋巴结及远处转移是PFS的独立预后因素（分别为P<0.001、P = 0.047、P = 0.001和P<0.001）。
MSI和CTCs可作为CRC患者生存率和预后的准确、可靠且敏感的诊断及预后生物标志物。
