Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers with Response to Neoadjuvant Chemotherapy.
Somatic FGFR3 Mutations Distinguish a Subgroup of Muscle-Invasive Bladder Cancers with Response to Neoadjuvant Chemotherapy.
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体细胞 FGFR3 突变可区分肌层浸润性膀胱癌亚组与新辅助化疗的反应
DOI：
10.1016/j.ebiom.2018.06.011
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发表时间：
2018-09
期刊：
影响因子：
11.1
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Yang Z;Zhang R;Ge Y;Qin X;Kang X;Wang Y;Zhang X;Song C;Quan X;Wang H;Chen H;Li C
在根治性膀胱切除术前给予新辅助化疗（NAC）有利于肌层浸润性膀胱癌（MIBC）患者的总生存率。然而，MIBC和NAC反应的基因谱之间的关系仍然不清楚。在此，开发了6种癌症相关基因（TSC 1、FGFR 3、TERT、TP 53、PIK 3CA和ERBB 2）的突变组和8种膀胱癌（BC）生物标志物（EGFR、RRM 1、PD-L1、BRCA 1、TUBB 3、ERCC、ERCC 1、异常糖基化整合素α3β1（AG）和CK 5/6）的免疫组织化学（IHC）组。将来自显示病理学应答（n = 39）和无应答（n = 13）的患者的BC样品应用于小组分析。ERBB 2、FGFR 3和PIK 3CA仅在缓解组中发生改变（19/39，48.7%），其中FGFR 3突变在队列中缓解的患者中显著富集（14/39，35.9%; P = 0.01）。此外，ERCC 1的强表达与病理反应相关（P = 0.01）。淋巴结转移（P < 0.01）和淋巴管浸润（P = 0.03）与无反应相关。总体而言，数据显示MIBCs中FGFR 3突变和ERCC 1表达升高是NAC应答的潜在预测生物标志物。FGFR 3改变与MIBC患者对NAC的病理反应相关。MIBC患者中ERCC 1的强表达与病理性NAC反应相关。MIBC患者中与NAC无应答相关的淋巴结转移和淋巴管浸润肌肉浸润性膀胱癌（MIBC）患者可能进展为转移，5年生存率<50%。新辅助化疗（NAC）已被证明对MIBC患者的总生存率有5-8%的益处。然而，遗传背景和MIBC化疗敏感性之间的关系仍然存在争议。Yang等发现FGFR 3突变和ERCC 1表达升高与MIBC患者的NAC应答相关。
The administration of neoadjuvant chemotherapy (NAC) preceding radical cystectomy benefits overall survival for patients with muscle-invasive bladder cancer (MIBC). However, the relationship between the genetic profiling of MIBC and NAC response remains unclear. Here, a mutation panel of six cancer-associated genes (TSC1, FGFR3, TERT, TP53, PIK3CA and ERBB2) and an immunohistochemistry (IHC) panel containing eight bladder cancer (BC) biomarkers (EGFR, RRM1, PD-L1, BRCA1, TUBB3, ERCC, ERCC1, aberrantly glycosylated integrin α3β1 (AG) and CK5/6) were developed. BC samples from patients who showed a pathologic response (n = 39) and non-response (n = 13) were applied to the panel analysis. ERBB2, FGFR3 and PIK3CA exclusively altered in the responders group (19/39, 48.7%), in which FGFR3 mutations were significantly enriched in patients with a response in the cohort (14/39, 35.9%; P = 0.01). Additionally, strong expression of ERCC1 was associated with a pathologic response (P = 0.01). However, positive lymph node metastasis (P < 0.01) and lymph-vascular invasion (LVI) (P = 0.03) were correlated with a non-response. Overall, the data show that FGFR3 mutations and elevated expression of ERCC1 in MIBCs are potential predictive biomarkers of the response to NAC. FGFR3 alterations are correlated with the pathologic response of MIBC patients to NAC. Strong ERCC1 expression in MIBC patients is associated with a pathologic NAC response. Lymph node metastasis and lymph-vascular invasion associated with non-response to NAC in MIBC patients. Patients with muscle-invasive bladder cancers (MIBCs) are likely progressed to metastasis and have a five-year survival <50%. Neoadjuvant chemotherapy (NAC) has been demonstrated to have an overall survival benefit of 5–8% for MIBC patients. However, the relationship between genetic background and MIBC chemosensitivity remains debatable. Yang et al. identified that the mutation of FGFR3 and the elevated expression of ERCC1 were correlated with NAC response in MIBC patients.
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影响因子：
158.5
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
Siefker-Radtke AO