Heterogeneity of MSI-H gastric cancer identifies a subtype with worse survival
Heterogeneity of MSI-H gastric cancer identifies a subtype with worse survival
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MSI-H 胃癌的异质性确定了生存率较差的亚型
DOI：
10.1136/jmedgenet-2019-106609
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发表时间：
2021-01-01
影响因子：
4
通讯作者：
Hu, Wangxiong
中科院分区：
文献类型：
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作者：
Yang, Yanmei;Shi, Zhong;Hu, Wangxiong
背景
由于存在大量非同义突变，微卫星高度不稳定（MSI-H）的肿瘤患者通常比微卫星稳定（MSS）的患者预后更好。然而，越来越多的研究表明，不到一半的MSI-H患者能从免疫检查点阻断治疗中获得生存获益或症状缓解。因此，迫切需要对异质性的MSI-H肿瘤进行深入研究。
方法
在此，我们利用基于非负矩阵分解（非NMF）的一致性聚类方法，对来自癌症基因组图谱以及亚洲队列GSE62254中的胃腺癌（STAD）样本进行分析，以确定MSI-H亚型。
结果
MSI-H的STAD样本基本可分为两个亚组（MSI-H1和MSI-H2）。对免疫微环境的进一步研究表明，免疫抑制因子在MSI-H1亚组中富集，这可能与该亚组预后较差有关。
结论
我们的研究结果揭示了MSI-H的STAD内部的遗传异质性，这对癌症患者的风险分层、预后评估和治疗具有重要意义。
Background Microsatellite instability-high (MSI-H) tumour patients generally have a better prognosis than microsatellite-stable (MSS) ones due to the large number of non-synonymous mutations. However, an increasing number of studies have revealed that less than half of MSI-H patients gain survival benefits or symptom alleviation from immune checkpoint-blockade treatment. Thus, an in-depth inspection of heterogeneous MSI-H tumours is urgently required. Methods Here, we used non-negative matrix factorisation (non-NMF)-based consensus clustering to define stomach adenocarcinoma (STAD) MSI-H subtypes in samples from The Cancer Genome Atlas and an Asian cohort, GSE62254. Results MSI-H STAD samples are basically clustered into two subgroups (MSI-H1 and MSI-H2). Further examination of the immune landscape showed that immune suppression factors were enriched in the MSI-H1 subgroup, which may be associated with the poor prognosis in this subgroup. Conclusions Our results illustrate the genetic heterogeneity within MSI-H STADs, with important implications for cancer patient risk stratification, prognosis and treatment.