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Abstract：
OBJECTIVE: To date, only a few studies have investigated the role of molecular alterations in cancer recurrence. This exploratory study aimed to evaluate the impact of molecular alterations on the time and site of recurrence in patients with stage I-IV CRC and to identify the risk factors predicting recurrence-free survival in colon cancer.
METHODS: A total of 270 patients were retrospectively included. We assessed the full RAS status using Sanger and pyrosequencing. MSI status was determined by immunohistochemical analysis. Molecular alterations were correlated with recurrence timing (early or late), recurrence patterns, and recurrence-free survival. Statistical analysis was performed using the Kaplan-Meier method and the log-rank test.
RESULTS: Of the 270 patients, 85 (31%) experienced recurrence, among whom 53% had mutant full RAS status, 48% had KRAS mutations, and 31.4% had KRAS p. G12V mutation subtype. Compared with those with late recurrence, patients with early recurrence were significantly older (P = 0.02) and more likely to have poorly differentiated tumors, a higher rate of positive lymph nodes, KRAS mutations, and especially KRAS p. G12V mutation variant. RAS mutation status, KRAS mutations, and rare mutations are more common in patients with lung cancer recurrence. Multivariate logistic regression analysis revealed that differentiation, perineural invasion, full RAS mutation status, and KRAS codon 13 mutations were independent factors for recurrence-free survival in colon cancer.
CONCLUSIONS: In this cohort, the timing and patterns of recurrence appeared to be associated with the patient\'s molecular profile. KRAS codon 12 mutations were the worst predictors of recurrence-free survival at all stages in our population.
METHODS: A total of 270 patients were retrospectively included. We assessed the full RAS status using Sanger and pyrosequencing. MSI status was determined by immunohistochemical analysis. Molecular alterations were correlated with recurrence timing (early or late), recurrence patterns, and recurrence-free survival. Statistical analysis was performed using the Kaplan-Meier method and the log-rank test.
RESULTS: Of the 270 patients, 85 (31%) experienced recurrence, among whom 53% had mutant full RAS status, 48% had KRAS mutations, and 31.4% had KRAS p. G12V mutation subtype. Compared with those with late recurrence, patients with early recurrence were significantly older (P = 0.02) and more likely to have poorly differentiated tumors, a higher rate of positive lymph nodes, KRAS mutations, and especially KRAS p. G12V mutation variant. RAS mutation status, KRAS mutations, and rare mutations are more common in patients with lung cancer recurrence. Multivariate logistic regression analysis revealed that differentiation, perineural invasion, full RAS mutation status, and KRAS codon 13 mutations were independent factors for recurrence-free survival in colon cancer.
CONCLUSIONS: In this cohort, the timing and patterns of recurrence appeared to be associated with the patient\'s molecular profile. KRAS codon 12 mutations were the worst predictors of recurrence-free survival at all stages in our population.
摘要：
目标：迄今为止，只有少数研究调查了分子改变在癌症复发中的作用。这项探索性研究旨在评估分子改变对I-IV期CRC患者复发时间和部位的影响，并确定预测结肠癌无复发生存的风险因素。
方法：回顾性纳入270例患者。我们使用Sanger和焦磷酸测序评估了完整的RAS状态。通过免疫组织化学分析确定MSI状态。分子改变与复发时间（早期或晚期）相关，复发模式，和无复发生存。使用Kaplan-Meier方法和对数秩检验进行统计分析。
结果：在270名患者中，85（31％）经历了复发，其中53%有突变完全RAS状态，48%有KRAS突变,31.4%有KRASp.G12V突变亚型。与晚期复发者相比，早期复发的患者明显年龄较大（P=0.02），并且更可能患有低分化肿瘤，淋巴结阳性率较高，KRAS突变,尤其是KRASp。G12V突变变体。RAS突变状态,KRAS突变,罕见突变在肺癌复发患者中更为常见。多因素Logistic回归分析显示，神经周浸润,完全RAS突变状态，KRAS密码子13突变是结肠癌无复发生存的独立因素.
结论：在这个队列中，复发的时间和模式似乎与患者的分子谱有关.KRAS密码子12突变是我们人群中所有阶段无复发生存的最差预测因子。
方法：回顾性纳入270例患者。我们使用Sanger和焦磷酸测序评估了完整的RAS状态。通过免疫组织化学分析确定MSI状态。分子改变与复发时间（早期或晚期）相关，复发模式，和无复发生存。使用Kaplan-Meier方法和对数秩检验进行统计分析。
结果：在270名患者中，85（31％）经历了复发，其中53%有突变完全RAS状态，48%有KRAS突变,31.4%有KRASp.G12V突变亚型。与晚期复发者相比，早期复发的患者明显年龄较大（P=0.02），并且更可能患有低分化肿瘤，淋巴结阳性率较高，KRAS突变,尤其是KRASp。G12V突变变体。RAS突变状态,KRAS突变,罕见突变在肺癌复发患者中更为常见。多因素Logistic回归分析显示，神经周浸润,完全RAS突变状态，KRAS密码子13突变是结肠癌无复发生存的独立因素.
结论：在这个队列中，复发的时间和模式似乎与患者的分子谱有关.KRAS密码子12突变是我们人群中所有阶段无复发生存的最差预测因子。
