PDF(Pubmed)
Abstract：
UNASSIGNED: Colorectal cancer (CRC) patients with BRAF mutation have very poor prognosis. It is urgent to search for prognostic factors of BRAF mutant CRC. RNF43 is a ENF ubiquitin ligase of Wnt signaling. Mutation of RNF43 has been observed frequently in various types of human cancers. However, few studies have evaluated the role of RNF43 in CRC. The present study aimed to explore the impact of RNF43 mutations on molecular characteristics and prognosis in BRAF mutant CRC.
UNASSIGNED: Samples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation.
UNASSIGNED: This study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC.
UNASSIGNED: Collectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.
UNASSIGNED: Samples of 261 CRC patients with BRAF mutation were retrospectively analyzed. Tumor tissue and matched peripheral blood samples were collected and subjected to targeted sequencing with a panel of 1021 cancer-related genes. The association of molecular characteristics and survival in patients were then analyzed. 358 CRC patients with BRAF mutation from the cBioPortal dataset were used for further confirmation.
UNASSIGNED: This study was inspired by a CRC patient with BRAF V600E and RNF43 co-mutation, who achieved a best remission of 70% and a progression free survival (PFS) of 13 months. Genomic analysis indicated that RNF43 mutation affected the genomic characteristics of patients with BRAF mutation, including microsatellite instability (MSI), tumor mutation burden (TMB) and the proportion of common gene mutations. Survival analysis showed that RNF43 mutation was a predictive biomarker for better PFS and OS in BRAF mutant CRC.
UNASSIGNED: Collectively, we identified that RNF43 mutations were correlated with favorable genomic features, resulting in a better clinical outcome for BRAF mutant CRC patients.
摘要：
■具有BRAF突变的结直肠癌（CRC）患者的预后非常差。迫切需要寻找BRAF突变CRC的预后因素。RNF43是Wnt信号传导的ENF泛素连接酶。在各种类型的人类癌症中经常观察到RNF43的突变。然而,很少有研究评估RNF43在CRC中的作用。本研究旨在探讨RNF43突变对BRAF突变CRC分子特征及预后的影响。
■对261例具有BRAF突变的CRC患者的样本进行回顾性分析。收集肿瘤组织和匹配的外周血样品,并用一组1021个癌症相关基因进行靶向测序。然后分析患者的分子特征与生存的关系。来自cBioPortal数据集的358例具有BRAF突变的CRC患者用于进一步确认。
■这项研究的灵感来自一位患有BRAFV600E和RNF43共突变的CRC患者，谁实现了70％的最佳缓解和13个月的无进展生存期（PFS）。基因组分析表明，RNF43突变影响了BRAF突变患者的基因组特征，包括微卫星不稳定性(MSI)，肿瘤突变负荷（TMB）和常见基因突变的比例。生存分析显示RNF43突变是BRAF突变CRC中更好的PFS和OS的预测生物标志物。
■集体，我们发现RNF43突变与有利的基因组特征相关，导致BRAF突变CRC患者的临床结局更好。
■对261例具有BRAF突变的CRC患者的样本进行回顾性分析。收集肿瘤组织和匹配的外周血样品,并用一组1021个癌症相关基因进行靶向测序。然后分析患者的分子特征与生存的关系。来自cBioPortal数据集的358例具有BRAF突变的CRC患者用于进一步确认。
■这项研究的灵感来自一位患有BRAFV600E和RNF43共突变的CRC患者，谁实现了70％的最佳缓解和13个月的无进展生存期（PFS）。基因组分析表明，RNF43突变影响了BRAF突变患者的基因组特征，包括微卫星不稳定性(MSI)，肿瘤突变负荷（TMB）和常见基因突变的比例。生存分析显示RNF43突变是BRAF突变CRC中更好的PFS和OS的预测生物标志物。
■集体，我们发现RNF43突变与有利的基因组特征相关，导致BRAF突变CRC患者的临床结局更好。
