ERBB2 Mutations as Potential Predictors for Recurrence in Colorectal Serrated Polyps by Targeted Next-Generation Sequencing

作者：Qiwen Wang, Xinyuan Wang, Qingwei Zhang, Jin-Nan Chen, Yujie Zhou, Zhao-Rong Tang, Ruilan Wang, Haoyan Chen, Haoyan Chen, Huimin Chen, Huimin Chen, Xiaobo Li · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.769709 · 被引用次数：5 · 研究领域：Colorectal Cancer Screening and Detection、Colorectal Cancer Treatments and Studies、Genetic factors in colorectal cancer

Background Follow-up guidelines for serrated polyps (SPs) are mainly based on factors such as histology and size with limited evidence. The underlying genomic mechanism of SPs in relation to recurrence risks is utterly unknown. Methods We applied targeted next-generation sequencing (NGS) approach on two groups of SPs [polyp-relapsed SPs (PRSPs) vs. polyp-free SPs (PFSPs)] based on the surveillance outcomes to compare differences of DNA variants in 71 colorectal cancer-associated genes. A multicenter validation cohort was established longitudinally from 2016 to 2019 to confirm the relevant results. Results Among the 96 NGS samples, at least one mutant after filtration was detected in 90 samples (94%). Molecular profiling presented BRAF , KRAS , and APC as top 3 mutated genes. FBXW7 , MSH2 , and ERBB2 might be recurrence-relevant, while DMD , BRCA1 , and BRCA2 might be negatively correlated with recurrence. Notably, ERBB2 mutants (R678Q and V842I) (n = 5) had higher risks of polyp recurrence than the wild types (n = 85), with a median polyp-free interval of 15 months compared to 26 months [P < 0.001; hazard ratio (HR) = 4.9; 95% confidence interval (CI) = 1.9–12.8]. Furthermore, a multicenter cohort composed by 321 SPs verified that ERBB2 -mutated SPs had increased risks of polyp recurrence (P < 0.001; HR = 3.7; 95% CI = 2.3–6.0) and advanced neoplastic lesion (ANL) recurrence (P < 0.001; HR = 10.0; 95% CI = 2.7–36.9) compared with wild-type SPs, respective...