Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
Tumor-Infiltrating Immune Cells Act as a Marker for Prognosis in Colorectal Cancer
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肿瘤浸润免疫细胞作为结直肠癌预后的标志物
DOI：
10.3389/fimmu.2019.02368
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发表时间：
2019-10-17
影响因子：
7.3
通讯作者：
Xue, Xiangyang
中科院分区：
文献类型：
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作者：
Ye, Lele;Zhang, Teming;Xue, Xiangyang
肿瘤浸润免疫细胞（TIICs）在癌症的发生和发展中起着重要作用。然而，TIICs与结直肠癌（CRC）患者预后的关系尚不明确。使用ssGSEA和CIBERSORT工具评估TIICs的浸润情况。通过从GEO （https://www.ncbi.nlm.nih.gov/geo/）和TCGA （https://portal.gdc.cancer.gov/）数据库下载的1802份CRC数据分析TIICs与预后的关系。选择CD66b+肿瘤相关中性粒细胞（TANs）、FoxP3+ Tregs和CD163+肿瘤相关巨噬细胞（TAMs） 3个TIICs群体，在1008例结直肠癌活检中进行免疫组化（IHC）验证分析，分析其对结直肠癌患者临床特征和预后的影响。基于训练队列（359例患者）构建预后模型。在测试（249例患者）和验证队列（400例患者）中对模型进行了进一步的测试和验证。基于ssGSEA和CIBERSORT分析，不同数据集的TIICs与CRC预后的相关性不一致。此外，同一数据集中无病生存期（DFS）和总生存期（OS）数据的结果也不同。ssGSEA或CIBERSORT工具发现的高丰度TIICs可有效用于预后评估。免疫组化结果显示，TANs、Tregs、TAMs与结直肠癌患者预后显著相关，为独立预后因素（PDFS≤0.001;POS≤0.023）。基于TANs、Tregs、TAMs的数量构建预后预测模型（C-indexDFS&OS = 0.86; AICDFS = 448.43; AICOS = 184.30），较传统的评价结直肠癌患者预后的指标更可靠。此外，TIICs可能影响对化疗的反应。综上所述，TIICs与结直肠癌患者的临床特征和预后相关，可作为标志物。
Tumor-infiltrating immune cells (TIICs) play essential roles in cancer development and progression. However, the association of TIICs with prognosis in colorectal cancer (CRC) patients remains elusive. Infiltration of TIICs was assessed using ssGSEA and CIBERSORT tools. The association of TIICs with prognosis was analyzed in 1,802 CRC data downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/) databases. Three populations of TIICs, including CD66b+ tumor-associated neutrophils (TANs), FoxP3+ Tregs, and CD163+ tumor-associated macrophages (TAMs) were selected for immunohistochemistry (IHC) validation analysis in 1,008 CRC biopsies, and their influence on clinical features and prognosis of CRC patients was analyzed. Prognostic models were constructed based on the training cohort (359 patients). The models were further tested and verified in testing (249 patients) and validation cohorts (400 patients). Based on ssGSEA and CIBERSORT analysis, the correlation between TIICs and CRC prognosis was inconsistent in different datasets. Moreover, the results with disease-free survival (DFS) and overall survival (OS) data in the same dataset also differed. The high abundance of TIICs found by ssGSEA or CIBERSORT tools can be used for prognostic evaluation effectively. IHC results showed that TANs, Tregs, TAMs were significantly correlated with prognosis in CRC patients and were independent prognostic factors (PDFS ≤ 0.001; POS ≤ 0.023). The prognostic predictive models were constructed based on the numbers of TANs, Tregs, TAMs (C-indexDFS&OS = 0.86; AICDFS = 448.43; AICOS = 184.30) and they were more reliable than traditional indicators for evaluating prognosis in CRC patients. Besides, TIICs may affect the response to chemotherapy. In conclusion, TIICs were correlated with clinical features and prognosis in patients with CRC and thus can be used as markers.