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首页> 美国卫生研究院文献>PLoS Clinical Trials >Copy number gains at chr3p25 and chr11p11 are associated with lymph node involvement and survival in muscle-invasive bladder tumors
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Copy number gains at chr3p25 and chr11p11 are associated with lymph node involvement and survival in muscle-invasive bladder tumors

机译：chr3p25和chr11p11处的拷贝数增加与肌肉浸润性膀胱肿瘤的淋巴结受累和生存有关

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Patients with muscle-invasive bladder cancer (MIBC) have poorer prognoses if cancer has metastasized to the lymph nodes. Genomic markers of lymph node involvement (LNI) would be useful for treatment planning, especially if measured at the biopsy stage, but large-scale studies of tumor tissue at any stage are needed to discover robust markers of LNI. We performed a genome-wide query of copy number alterations (CNA) in 237 MIBC surgical tumor specimens from patients in The Cancer Genome Atlas who had radical cystectomy and lymphadenectomy without neoadjuvant treatment. Pathology reports were independently reviewed to confirm LNI, and copy number data was analyzed to confirm gene-level gains and losses while adjusting for tumor purity and ploidy. Using logistic regression and elastic net models, we identified the CNA most significantly associated with LNI. Multivariable logistic regression was used to describe these CNA associations while adjusting for clinical variables. Kaplan-Meier and Cox regression were used to describe their association with overall survival. Gains in 26 genes were identified as having strong associations with LNI. After adjusting for age, gender, race, pathological tumor stage, histology, and number of nodes examined, gains in 22 genes on chr3p25 or chr11p11 remained significantly associated with LNI (p<0.01) and improved model discrimination over clinical variables alone (p = 0.04). They were also associated with shorter overall survival (adjusted p = 0.02). These results suggest that a simple genomic test for gains in chr3p25 and chr11p11 could inform adjuvant treatment or clinical trial decisions if validated in external cohorts. Additional studies will also be needed to determine if these CNA are detectible in biopsy tissue and can inform clinical decisions at the preoperative stage.
机译：如果癌症转移到淋巴结，则患有肌肉浸润性膀胱癌（MIBC）的患者预后较差。淋巴结受累（LNI）的基因组标记物可用于治疗计划，特别是如果在活检阶段进行测量时，但需要在任何阶段进行肿瘤组织的大规模研究，以发现强大的LNI标记物。我们对来自癌症基因组图谱患者的237例MIBC外科肿瘤标本进行了全基因组范围内的拷贝数变化（CNA）查询，这些患者接受了根治性膀胱切除术和淋巴结切除术而没有新辅助治疗。独立审查病理报告以确认LNI，并分析拷贝数数据以确认基因水平的得失，同时调整肿瘤的纯度和倍性。使用逻辑回归和弹性网模型，我们确定了与LNI最相关的CNA。在调整临床变量时，使用多变量logistic回归描述这些CNA关联。 Kaplan-Meier和Cox回归用于描述其与总生存期的关系。鉴定出26个基因的增益与LNI有很强的关联。在调整了年龄，性别，种族，病理性肿瘤分期，组织学和检查的淋巴结数目之后，chr3p25或chr11p11上22个基因的增加仍与LNI显着相关（p <0.01），并且仅基于临床变量就改善了模型辨别力（p = 0.04）。它们还与较短的总生存期相关（调整后的p = 0.02）。这些结果表明，如果在外部队列中进行了验证，那么对chr3p25和chr11p11进行的简单基因组测试可以为辅助治疗或临床试验决策提供依据。还需要其他研究来确定这些CNA是否在活检组织中可检测到，并且可以在术前阶段为临床决策提供依据。

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