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Abstract：
BACKGROUND: RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described.
OBJECTIVE: To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC.
METHODS: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression.
RESULTS: The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors.
CONCLUSIONS: This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.
OBJECTIVE: To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC.
METHODS: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression.
RESULTS: The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors.
CONCLUSIONS: This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.
摘要：
背景：RAS，BRAF,和错配修复（MMR）/微卫星不稳定性（MSI）是结直肠癌（CRC）临床实践指南推荐的关键生物标志物。然而,中国患者的特征和影响因素尚未得到全面描述。
目的：分析KRAS的临床病理特征，NRAS,BRAF,和PIK3CA突变和CRC中的DNAMMR状态。
方法：我们在中日友好医院招募了2271例中国CRC患者。MMR蛋白使用免疫组织化学分析进行测试，使用定量聚合酶链反应确定KRAS/NRAS/BRAF/PIK3CA突变。使用MSI检测试剂盒确定微卫星状态。采用SPSS软件和logistic回归进行统计分析。
结果：KRAS，NRAS,BRAF,检测到PIK3CA突变占44.6%,3.4%,3.7%,3.9%的CRC患者，分别。KRAS突变更可能发生在中高分化患者中。BRAF突变更可能发生在右侧CRC患者中，分化差,或者没有神经周侵犯。在所有患者中的7.9％和粘液性腺癌患者中的16.8％中检测到缺陷MMR（dMMR）。KRAS,NRAS,BRAF,和PIK3CA突变检测29.6%,1.1%,8.1%,22.3%的dMMR患者，分别。dMMR更可能发生在有CRC家族史的患者中，年龄<50岁，右侧CRC，低分化组织学，无神经周侵犯,原位癌，阶段I,或II期肿瘤。
结论：这项研究分析了KRAS的分子谱，NRAS,BRAF,PIK3CA,和CRC中的MMR/MSI，确定关键影响因素，对CRC临床管理的影响。
目的：分析KRAS的临床病理特征，NRAS,BRAF,和PIK3CA突变和CRC中的DNAMMR状态。
方法：我们在中日友好医院招募了2271例中国CRC患者。MMR蛋白使用免疫组织化学分析进行测试，使用定量聚合酶链反应确定KRAS/NRAS/BRAF/PIK3CA突变。使用MSI检测试剂盒确定微卫星状态。采用SPSS软件和logistic回归进行统计分析。
结果：KRAS，NRAS,BRAF,检测到PIK3CA突变占44.6%,3.4%,3.7%,3.9%的CRC患者，分别。KRAS突变更可能发生在中高分化患者中。BRAF突变更可能发生在右侧CRC患者中，分化差,或者没有神经周侵犯。在所有患者中的7.9％和粘液性腺癌患者中的16.8％中检测到缺陷MMR（dMMR）。KRAS,NRAS,BRAF,和PIK3CA突变检测29.6%,1.1%,8.1%,22.3%的dMMR患者，分别。dMMR更可能发生在有CRC家族史的患者中，年龄<50岁，右侧CRC，低分化组织学，无神经周侵犯,原位癌，阶段I,或II期肿瘤。
结论：这项研究分析了KRAS的分子谱，NRAS,BRAF,PIK3CA,和CRC中的MMR/MSI，确定关键影响因素，对CRC临床管理的影响。
