Tuft cell-like carcinomas: novel cancer subsets present in multiple organs sharing a unique gene expression signature
Tuft cell-like carcinomas: novel cancer subsets present in multiple organs sharing a unique gene expression signature
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DOI：
10.1038/s41416-022-01957-6
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发表时间：
2022-08-23
影响因子：
8.8
通讯作者：
Marx, Alexander
中科院分区：
文献类型：
--
作者：
Yamada, Yosuke;Bohnenberger, Hanibal;Marx, Alexander
背景毛簇细胞是一种化学感受性上皮细胞，在天然免疫中起重要作用。最近的研究揭示了在胸部具有簇状细胞样基因表达特征的癌症。我们想知道这种特征是否也可能发生在胸外癌中。方法应用肿瘤基因组图谱（TCGA）检测19例不同类型胸外多器官癌组织中簇状细胞标志物（POU2F3、GFI1B、TRPM5、SOX 9、CHAT和AVIL）的mRNA表达。通过免疫组化分析了我们当地档案中的四种不同胸外癌（N = 909）。结果22例（0.35%）胸外肿瘤与POU2F3和其他簇状细胞标记物的共表达在各种TCGA数据集中被确定。22个"簇状细胞样肿瘤"中的12个共享分化差和基因表达模式，包括KIT、抗凋亡BCL 2和离子细胞相关基因。在我们的存档病例中，11例（1.21%）肿瘤在免疫组织化学上共表达POU2F3、KIT和BCL 2，即，可能是簇状细胞样癌在5个TCGA队列中的3个中，簇状细胞样癌症亚群表达SLFN 11，这是一种有希望的PARP抑制剂敏感性生物标志物。结论在多种器官的肿瘤中，簇状细胞样癌形成不同的亚型。似乎有必要研究它们共享的基因表达特征作为新治疗策略的预测生物标志物。
Background Tuft cells are chemosensory epithelial cells playing a role in innate immunity. Recent studies revealed cancers with a tuft cell-like gene expression signature in the thorax. We wondered whether this signature might also occur in extrathoracic cancers. Methods We examined mRNA expression of tuft cell markers (POU2F3, GFI1B, TRPM5, SOX9, CHAT, and AVIL) in 19 different types of cancers in multiple extrathoracic organs with The Cancer Genome Atlas (TCGA) (N = 6322). Four different extrathoracic cancers in our local archives (N = 909) were analysed by immunohistochemistry. Results Twenty-two (0.35%) extrathoracic tumours with co-expression of POU2F3 and other tuft cell markers were identified in various TCGA datasets. Twelve of the 22 "tuft cell-like tumours" shared poor differentiation and a gene expression pattern, including KIT, anti-apoptotic BCL2, and ionocyte-associated genes. In our archival cases, eleven (1.21%) tumours co-expressing POU2F3, KIT, and BCL2 on immunohistochemistry, i.e., were presumable tuft cell-like cancers. In three among five TCGA cohorts, the tuft cell-like cancer subsets expressed SLFN11, a promising biomarker of PARP inhibitor susceptibility. Conclusions Tuft cell-like carcinomas form distinct subsets in cancers of many organs. It appears warranted to investigate their shared gene expression signature as a predictive biomarker for novel therapeutic strategies.