The treatment strategies and prognoses of patients with metastatic colorectal cancer (CRC) differ according to the sidedness of the primary tumor.TP53gain-of-function (GOF) and non-GOF variants have been reported to be differentially associated with prognosis by sidedness. We aimed to evaluate the sidedness-dependent prognostic impact of gene alterations in metastatic CRC. Patients enrolled between April 2017 and March 2019 were included in this study. Those excluded were individuals whose tumor tissues were obtained after chemotherapy and those who were enrolled in the study more than six months after starting first-line chemotherapy. Finally, we assessed 531 patients who underwent complete gene sequencing. The study revealed a significant difference in overall survival between individuals with left-sided CRC (n= 355) and right-sided colon cancer (CC) (n= 176) when considering theTP53non-GOF variant,KRASwild-type,NOTCH1wild-type,NOTCH1covariant,NOTCH3sole variant, andMYCamplification. Multivariate analysis on each side revealed that theTP53GOF andKRASvariants were independent poor prognostic factors for left-sided CRC (p= 0.03 andp< 0.01, respectively), and theTP53non-GOF variant,BRAFV600E, andMYCamplification for right-sided CC (p< 0.05,p< 0.01, andp= 0.02, respectively). TheNOTCH3sole variant was an independent and favorable prognostic factor for left-sided CRC (p< 0.01). The prognostic significance of gene alterations differed between left-sided CRC and right-sided CC.
转移性结直肠癌（CRC）患者的治疗策略和预后因原发肿瘤的侧向性而异。据报道，TP53功能获得性（GOF）与非GOF变异与不同侧向性的预后存在差异关联。本研究旨在评估转移性CRC中基因改变与侧向性相关的预后影响。纳入2017年4月至2019年3月期间入组的患者，排除标准包括化疗后获取肿瘤组织的个体以及开始一线化疗超过六个月后入组的患者。最终，我们对531例完成全基因测序的患者进行了评估。研究显示，在考虑TP53非GOF变异、KRAS野生型、NOTCH1野生型、NOTCH1共变异、NOTCH3单一变异及MYC扩增的情况下，左侧CRC（n=355）与右侧结肠癌（CC）（n=176）患者的总生存期存在显著差异。对各侧向性进行多变量分析发现，TP53 GOF变异和KRAS变异是左侧CRC的独立不良预后因素（分别为p=0.03和p<0.01），而TP53非GOF变异、BRAF V600E及MYC扩增是右侧CC的独立不良预后因素（分别为p<0.05、p<0.01和p=0.02）。NOTCH3单一变异是左侧CRC的独立有利预后因素（p<0.01）。基因改变的预后意义在左侧CRC与右侧CC之间存在显著差异。
肿瘤(癌症)患者之家