Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients
Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients
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DOI：
10.1007/s12282-023-01449-2
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发表时间：
2023-03-17
期刊：
影响因子：
4
通讯作者：
Wakai，Toshifumi
中科院分区：
文献类型：
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作者：
Nagahashi，Masayuki;Ling，YiWei;Wakai，Toshifumi
背景下一代测序（NGS）已使全面的基因组分析，以确定在癌症生物学中发挥重要作用的基因改变。然而，这些基因组改变在三阴性乳腺癌（TNBC）患者中的临床意义尚未完全阐明。本研究的目的是阐明基因组分析数据的临床意义，包括拷贝数改变（CNA）和肿瘤突变负荷（TMB），在TNBC patients.MethodsA共47例患者的阶段I-III TNBC与基因组分析435已知的癌症基因NGS被纳入本研究。结果CNA高表达患者的无病生存率（DFS）和总生存率（OS）明显低于CNA低表达患者（p= 0.0009，p = 0.0041）。TMB与TNBC患者的DFS或OS无关。TP 53基因突变患者的DFS（p= 0.0953）和OS（p= 0.0338）明显低于TP 53基因突变患者。包括CNA和其他临床病理参数的多变量分析显示，CNA是DFS（p= 0.0104）和OS（p= 0.0306）的独立预后因素。最后，多变量分析还显示CNA高和TP 53改变的组合是DFS（p= 0.0005）和OS（p= 0.0023.ConclusionsWe揭示CNA，而不是TMB，与TNBC患者的DFS和OS显著相关。CNA高和TP 53改变的组合可能是一种有前途的生物标志物，可以提供超出标准临床病理因素的信息，以识别预后显著较差的TNBC患者亚组。
BackgroundNext-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients.MethodsA total of 47 patients with Stage I–III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data.ResultsCNA-high patients showed significantly worse DFS and OS than CNA-low patients (p= 0.0009,p= 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients withTP53alterations showed a tendency of worse DFS (p= 0.0953) and significantly worse OS (p= 0.0338) compared with patients withoutTP53alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p= 0.0104) and OS (p= 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high andTP53alterations is an independent prognostic factor for DFS (p= 0.0005) and OS (p= 0.0023).ConclusionsWe revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high andTP53alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.