The Notch signalling pathway is involved in the development of several cancers, including colorectal cancer (CRC). However, whether mutations in this pathway could alter the CRC immunophenotype remains unknown. Here, we investigated the relationship between Notch signalling pathway mutations and the tumour immune microenvironment by analysing gene expression data from the GSE108989 single T cell RNA sequencing data set and The Cancer Genome Atlas (TCGA) data set. We found that Notch signalling pathway mutations were associated with an increased number of tumour‐specific CD8⁺ T cells and decreased number of inhibitory regulatory T (Treg) cells, representing an enhanced anti‐tumour response in the GSE108989 data set. In TCGA data set, we also found that Notch signalling pathway mutations were associated with enrichment of genes associated with immune activation pathways and higher expressions of PDCD1, GZMB and PRF1. Although Notch signalling pathway mutations did not affect the overall survival and disease‐free survival of CRC patients, they were associated with earlier disease stages and lower rates of metastasis. These results demonstrated that Notch signalling pathway mutations can enhance anti‐tumour immunity in CRC, as validated by the two data sets, suggesting that they may be promising biomarkers for immune checkpoint blockade therapies for CRC patients.

中文翻译：

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Notch信号通路中的突变与结直肠癌中增强的抗肿瘤免疫力有关。

Notch信号通路参与多种癌症的发展，包括结直肠癌（CRC）。然而，该途径中的突变是否会改变CRC免疫表型尚不清楚。在这里，我们通过分析来自GSE108989单T细胞RNA测序数据集和癌症基因组图谱（TCGA）数据集的基因表达数据，研究了Notch信号通路突变与肿瘤免疫微环境之间的关系。我们发现，Notch信号通路突变与肿瘤特异性CD8 ⁺数量增加有关T细胞和抑制性调节性T（Treg）细胞数量减少，代表GSE108989数据集中增强的抗肿瘤反应。在TCGA数据集中，我们还发现Notch信号通路突变与免疫激活通路相关基因的丰富以及PDCD1，GZMB和PRF1的高表达有关。尽管Notch信号通路突变不会影响CRC患者的总体生存率和无病生存期，但它们与疾病早期阶段和较低的转移率相关。这些结果表明，Notch信号通路突变可以增强CRC的抗肿瘤免疫力，这两个数据集均证实了这一点，表明它们可能是CRC患者免疫检查点封锁疗法的有前途的生物标志物。