神经内分泌肿瘤相关嗜铬细胞瘤和副神经节瘤的免疫特征与预后的关系。
Immune signature of pheochromocytoma and paraganglioma in context of neuroendocrine neoplasms associated with prognosis.
机构信息
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
Department of Medical Biology, Faculty of Science, University of South Bohemia, Ceske Budejovice, 37005, Czech Republic.
出版信息
Endocrine. 2023 Jan;79(1):171-179. doi: 10.1007/s12020-022-03218-1. Epub 2022 Nov 12.
PURPOSE
To understand prognostic immune cell infiltration signatures in neuroendocrine neoplasms (NENs), particularly pheochromocytoma and paraganglioma (PCPG), we analyzed tumor transcriptomic data from The Cancer Genome Atlas (TCGA) and other published tumor transcriptomic data of NENs.
METHODS
We used CIBERSORT to infer immune cell infiltrations from bulk tumor transcriptomic data from PCPGs, in comparison to gastroenteropancreatic neuroendocrine tumors (GEPNETs) and small cell lung carcinomas (SCLCs). PCPG immune signature was validated with NanoString immune panel in an independent cohort. Unsupervised clustering of the immune infiltration scores from CIBERSORT was used to find immune clusters. A prognostic immune score model for PCPGs and the other NENs were calculated as a linear combination of the estimated infiltration of activated CD8/CD4 T cells, activated NK cells, and M0 and M2 macrophages.
RESULTS
In PCPGs, we found five dominant immune clusters, associated with M2 macrophages, monocytes, activated NK cells, M0 macrophages and regulatory T cells, and CD8/CD4 T cells respectively. Non-metastatic tumors were associated with activated NK cells and metastatic tumors were associated with M0 macrophages and regulatory T cells. In GEPNETs and SCLCs, M0 macrophages and regulatory T cells were associated with unfavorable outcomes and features, such as metastasis and high-grade tumors. The prognostic immune score model for PCPGs and the NENs could predict non-aggressive and non-metastatic diseases. In PCPGs, the immune score was also an independent predictor of metastasis-free survival in a multivariate Cox regression analysis.
CONCLUSION
The transcriptomic immune signature in PCPG correlates with clinical features like metastasis and prognosis.
目的
为了了解神经内分泌肿瘤（NENs），尤其是嗜铬细胞瘤和副神经节瘤（PCPG）的预后免疫细胞浸润特征，我们分析了来自癌症基因组图谱（TCGA）和其他已发表的 NEN 肿瘤转录组数据的肿瘤转录组数据。
方法
我们使用 CIBERSORT 从 PCPG 的肿瘤转录组数据中推断免疫细胞浸润情况，并与胃肠胰腺神经内分泌肿瘤（GEPNETs）和小细胞肺癌（SCLCs）进行比较。在独立队列中使用 NanoString 免疫面板验证 PCPG 免疫特征。使用 CIBERSORT 的免疫浸润评分无监督聚类来找到免疫簇。计算 PCPG 和其他 NEN 的预后免疫评分模型，作为估计的激活 CD8/CD4 T 细胞、激活 NK 细胞以及 M0 和 M2 巨噬细胞浸润的线性组合。
结果
在 PCPG 中，我们发现了五个主要的免疫簇，分别与 M2 巨噬细胞、单核细胞、激活的 NK 细胞、M0 巨噬细胞和调节性 T 细胞以及 CD8/CD4 T 细胞相关。非转移性肿瘤与激活的 NK 细胞相关，而转移性肿瘤与 M0 巨噬细胞和调节性 T 细胞相关。在 GEPNETs 和 SCLCs 中，M0 巨噬细胞和调节性 T 细胞与不良结局和特征相关，如转移和高级别肿瘤。PCPG 和 NEN 的预后免疫评分模型可预测非侵袭性和非转移性疾病。在 PCPG 中，免疫评分在多变量 Cox 回归分析中也是无转移生存的独立预测因子。
结论
PCPG 的转录组免疫特征与转移和预后等临床特征相关。
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