Enhancing the landscape of colorectal cancer using targeted deep sequencing.
Enhancing the landscape of colorectal cancer using targeted deep sequencing.
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DOI：
10.1038/s41598-021-87486-3
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发表时间：
2021-04-14
影响因子：
4.6
通讯作者：
Lee SH
中科院分区：
文献类型：
--
作者：
Lee CS;Song IH;Lee A;Kang J;Lee YS;Lee IK;Song YS;Lee SH
靶向下一代测序（NGS）技术检测特定的突变，可以为结直肠癌（CRC）患者提供治疗机会。我们纳入了145例接受手术的结直肠癌患者。我们使用靶向NGS分析了常见可操作基因的突变频率及其与临床病理特征和肿瘤结果的关系。约97.9%（142例）的患者出现体细胞突变。在TP53（70%）、APC（60%）和KRAS（49%）中观察到频繁突变。TP53突变与较高的总分期（p = 0.038）和较低的无病生存（DFS） （p = 0.039）显著相关。ATM突变与较高的肿瘤分期（p = 0.012）和较短的总生存期（p = 0.041）显著相关。ATM突变（p = 0.023）的3期和4期患者的OS较短，FBXW7突变与DFS较短显著相关（p = 0.002）。然而，TP53、RAS、APC、PIK3CA和SMAD4突变患者的OS差异无统计学意义（p分别为0.59、0.72、0.059、0.25和0.12）。同样，RAS、APC、PIK3CA、SMAD4突变与野生型患者的DFS差异无统计学意义（p分别为0.3、0.79、0.13、0.59）。在多因素Cox回归分析中，ATM突变是OS不良预后的独立生物标志物（p = 0.043）。对结直肠癌分子标志物的全面分析可以提供对疾病进展机制的深入了解，并有助于优化个性化治疗。
Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), APC (60%), and KRAS (49%). TP53 mutations were significantly linked to higher overall stage (p = 0.038) and lower disease-free survival (DFS) (p = 0.039). ATM mutation was significantly associated with higher tumor stage (p = 0.012) and shorter overall survival (OS) (p = 0.041). Stage 3 and 4 patients with ATM mutations (p = 0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p = 0.002). However, the OS of patients with or without TP53, RAS, APC, PIK3CA, and SMAD4 mutations did not differ significantly (p = 0.59, 0.72, 0.059, 0.25, and 0.12, respectively). Similarly, the DFS between patients with RAS, APC, PIK3CA, and SMAD4 mutations and those with wild-type were not statistically different (p = 0.3, 0.79, 0.13, and 0.59, respectively). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p = 0.043). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.
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