Pathology Department, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
Department of Radiation Oncology, National Cancer Institute, Cairo University, Cairo, 11976, Egypt.
Mol Biol Rep. 2020 Dec;47(12):9645-9657. doi: 10.1007/s11033-020-05973-8. Epub 2020 Nov 10.
Rectal cancer is a common malignancy with a relatively poor prognosis. We assessed the possible prognostic and predictive role(s) of circulating tumor cells (CTCs) and K-ras mutations in locally advanced rectal carcinoma (LARC) patients. CTCs number and K-ras mutation status were assessed in the Peripheral blood and tumor tissue samples of 60 patients with LARC compared to control group (normal rectal mucosa). Data were correlated to relevant clinico-pathological features, response to treatment, disease free (DFS) and overall survival (OS) rates. K-ras mutations were present in 24/60 (40%) patients. Baseline CTCs (< 5 cells/7 ml blood) were detected in 23/60 (38.3%) patients, and 37 (61.7%) had baseline CTCs (≥ 5 cells/7 ml) blood (P = 0.071). Serial sampling showed a decrease in CTCs levels in 40 (66.7%) patients and increase in 20 (33.3%) patients (P = 0.01). Patients with K-ras mutations had a significantly poor response to treatment, with reduced DFS and OS rates (P = 0.001, 0.004, and 0.001; respectively). Similarly, decreased CTCs levels during treatment associated significantly with better pathological responses (P = 0.003). Multivariate analysis demonstrated that K-ras mutation and baseline CTCs are independent prognostic factors for DFS (P = 0.014 and 0.045; respectively) and OS (P = 0.002 and 0.045; respectively). The presence of mutant K-ras and baseline CTCs ≥ 5 cells associated significantly with poor pathological response, shorter DFS and OS rates compared to those with either K-ras mutation or CTCs ≥ 5 cells only (P = 0.014, 0.005 and 0.001, respectively). K-ras mutations, baseline and serial CTCs changes represent good prognostic and predictive factors for LARC patients.
直肠癌是一种预后较差的常见恶性肿瘤。我们评估了循环肿瘤细胞（CTC）和 K-ras 突变在局部晚期直肠癌（LARC）患者中的可能预后和预测作用。与对照组（正常直肠黏膜）相比，我们评估了 60 例 LARC 患者外周血和肿瘤组织样本中的 CTC 数量和 K-ras 突变状态。将数据与相关临床病理特征、治疗反应、无病生存（DFS）和总生存（OS）率相关联。24/60（40%）例患者存在 K-ras 突变。基线时（<5 个细胞/7ml 血液）检测到 23/60（38.3%）例患者存在 CTCs，37（61.7%）例患者基线 CTCs（≥5 个细胞/7ml）血液（P=0.071）。连续采样显示 40（66.7%）例患者 CTCs 水平下降，20（33.3%）例患者 CTCs 水平升高（P=0.01）。K-ras 突变患者对治疗的反应明显较差，DFS 和 OS 率降低（P=0.001、0.004 和 0.001；分别）。同样，治疗期间 CTCs 水平降低与更好的病理反应显著相关（P=0.003）。多变量分析表明，K-ras 突变和基线 CTCs 是 DFS（P=0.014 和 0.045；分别）和 OS（P=0.002 和 0.045；分别）的独立预后因素。与仅存在 K-ras 突变或 CTCs≥5 个细胞的患者相比，存在突变型 K-ras 和基线 CTCs≥5 个细胞的患者与较差的病理反应、较短的 DFS 和 OS 率显著相关（P=0.014、0.005 和 0.001；分别）。K-ras 突变、基线和连续 CTCs 变化是 LARC 患者的良好预后和预测因素。
