下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma.
原发肿瘤队列在调整重要预后因素后,未显示NY-ESO-1表达与OS之间存在关联(包括按HLA-A∗02亚型和治疗线数进行分层),这可能是由于样本量较小所致。
为了更好地理解纽约食管鳞状细胞癌1(NY-ESO-1)和人类白细胞抗原(HLA)亚型在治疗决策中的重要性,需要进一步研究它们在转移性滑膜肉瘤(mSS)患者中的患病率和预后影响。
这是一项针对mSS成人患者的回顾性临床生物学队列研究。患者数据收集自法国肉瘤组NetSARC数据库,并通过电子病历进行补充。收集原发肿瘤样本,通过免疫组织化学(IHC)分析NY-ESO-1表达,通过RNA测序(RNA-seq)分析HLA-A∗02状态。主要队列包括有可用原发肿瘤样本的患者;通过纳入有原发或转移样本的患者(称为探索性队列)来探讨更大样本量的影响。P值仅供描述性目的提供。
在92例有原发肿瘤样本的患者中,约25%(n = 23)为NY-ESO-1和HLA-A∗02表达阳性(双阳性)。在106例有IHC数据的患者中,61%(n = 65)为NY-ESO-1阳性,在94例有RNA-seq数据的患者中,45%(n = 42)为HLA-A∗02阳性。NY-ESO-1阳性与阴性的中位OS分别为35.3个月和21.7个月(未校正P = 0.0428)。我们观察到HLA-A∗02阳性与阴性患者之间、以及双阳性患者与其他患者之间的中位OS均无差异(未校正P均> 0.05)。OS的多因素分析显示,NY-ESO-1在原发肿瘤样本和探索性队列中均无预后影响。然而,在后一队列中,我们观察到NY-ESO-1表达与OS在一线治疗中相关(P = 0.0041),但在二线治疗中不相关。
BACKGROUND: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed. PATIENTS AND METHODS: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes. RESULTS: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting. CONCLUSIONS: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes.
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