Prognostic significance of tumor-infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large-scale cohort study
Prognostic significance of tumor-infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large-scale cohort study
复制标题
肿瘤浸润淋巴细胞在非播散性鼻咽癌中的预后意义：一项大规模队列研究
DOI：
10.1002/ijc.31279
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发表时间：
2018-06-15
影响因子：
6.4
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Wang, Ya-Qin;Chen, Yu-Pei;Ma, Jun
美国癌症联合委员会(AJCC)的分期系统不足以准确预测鼻咽癌(NPC)的预后。因此，新的生物标记物正在紧张的研究中。在这里，我们研究TIL密度是否可以预测鼻咽癌的预后。首先，我们使用来自两个独立队列的1490例鼻咽癌标本来评估肿瘤浸润性淋巴细胞(TIL)的密度和分布。其次，在一个队列中，我们评估了593个随机选择的样本(定义为训练集)和其余593个样本(定义为验证集)的验证结果与TIL和临床结果之间的关系。此外，我们在304例患者(定义为独立组)的第二个独立队列中证实了TIL的预后价值。基于多变量COX回归分析，我们还建立了包括TILs的有效预后诺模图，以提高预测非播散型鼻咽癌患者无病生存(DFS)的准确性。我们发现，训练集中的高TIL与有利的DFS[风险比(HR)0.41，95%可信区间(CI)0.28-0.58，p<；0.001]、总生存率(OS，HR 0.42，95%CI 0.27-0.64，p&t；0.001)、无远处转移生存率(DMFS，HR 0.37，95%CI 0.23-0.58，p<；)显著相关。局部-区域无复发生存率(LRRFS，HR0.43，95%CI0.25~0.73，p=0.002)。多因素分析显示，在所有队列中，TIL是DFS的独立预后指标。综上所述，本研究提示TIL可能反映鼻咽癌的免疫异质性，并可作为一种新的预后生物标志物。
The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease-free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.58, p < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27-0.64, p < 0.001), distant metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23-0.58, p < 0.001) and local-regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25-0.73, p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.