Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis.
Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis.
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DOI：
10.21037/atm-20-922
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发表时间：
2020-09
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
He Y;Wang X
尽管免疫疗法在治疗包括具有DNA错配修复缺陷的胃癌（GC）在内的各种难治性恶性肿瘤方面取得了成功，但只有一部分癌症患者对免疫疗法有反应。因此，迫切需要鉴定用于改善癌症免疫治疗反应的有用生物标志物或干预靶点。我们使用三个多组学GC数据集研究了各种分子特征和免疫特征之间的关联。这些分子特征包括基因、microRNA（miRNA）、长链非编码RNA（lncRNA）、蛋白质和途径，免疫特征包括CD 8 + T细胞浸润、免疫细胞溶解活性（伊卡）和PD-L1表达。此外，我们研究了接受免疫治疗的胃肠道（GI）癌症队列和未接受这种治疗的两个GC队列中基因突变与生存预后之间的关联。一些重要的癌基因和抑癌基因的突变与GC中的免疫特征明显相关，包括PIK 3CA、MTOR、RNF 213、TP 53、ARID 1A、PTEN、ATM和CDH 1。此外，许多基因在GC中表现出与免疫特征显著的表达相关性，包括CXCL 9、CXCL 13、CXCR 6、CCL 5、GUCY 2C、MAP 3 K9、NEK 3、PAK 6、STK 35和WNK 2。我们鉴定了几种蛋白质，其表达与GC中的免疫特征显著正相关。这些蛋白包括caspase-7、PI 3 K-p85、PREX 1、Lck、Bcl-2和转氨酶。相比之下，乙酰辅酶A羧化酶（ACC）的表达与GC中的免疫特征呈显着负相关，表明抑制ACC可以增强GC的抗肿瘤免疫力。此外，我们鉴定了许多与GC免疫具有显著表达相关性的miRNA和lncRNA，包括hsa-miR-150、155、142、342、146、101、511、29、AC022706.1、LINC 01871和AC006033.2。我们还鉴定了许多癌症相关通路，其活性与GC免疫相关，包括mTOR、PI 3 K-AKT、MAPK、HIF-1和VEGF信号通路。有趣的是，我们发现七个基因（ARID 1A、BCOR、MTOR、CREBBP、SPEN、NOTCH 4和TET 1）的突变与接受抗PD-1/PD-L1免疫治疗的GI癌症患者的OS更好相关，但与未接受免疫治疗的GC患者的OS无关。与GC免疫显著相关的分子特征可能是有用的生物标志物，用于分层GC患者对免疫治疗或干预靶点的反应，以促进GC的抗肿瘤免疫和免疫治疗反应。
Although immunotherapy has achieved success in treating various refractory malignancies including gastric cancers (GCs) with DNA mismatch repair deficiency, only a subset of cancer patients are responsive to immunotherapy. Therefore, the identification of useful biomarkers or interventional targets for improving cancer immunotherapy response is urgently needed. We investigated the associations between various molecular features and immune signatures using three multi-omics GC datasets. These molecular features included genes, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), proteins, and pathways, and the immune signatures included CD8+ T cell infiltration, immune cytolytic activity (ICA), and PD-L1 expression. Moreover, we investigated the association between gene mutations and survival prognosis in a gastrointestinal (GI) cancer cohort receiving immunotherapy and two GC cohorts not receiving such a therapy. The mutations of some important oncogenes and tumor suppressor genes were appreciably associated with immune signatures in GC, including PIK3CA, MTOR, RNF213, TP53, ARID1A, PTEN, ATM, and CDH1. Moreover, a number of genes exhibited a significant expression correlation with immune signatures in GC, including CXCL9, CXCL13, CXCR6, CCL5, GUCY2C, MAP3K9, NEK3, PAK6, STK35, and WNK2. We identified several proteins whose expression had a significant positive correlation with immune signatures in GC. These proteins included caspase-7, PI3K-p85, PREX1, Lck, Bcl-2, and transglutaminase. In contrast, acetyl-CoA carboxylase (ACC) had a significant inverse expression correlation with immune signatures in GC, suggesting that inhibiting ACC could enhance antitumor immunity in GC. Furthermore, we identified numerous miRNAs and lncRNAs with a significant expression correlation with GC immunity, including hsa-miR-150, 155, 142, 342, 146, 101, 511, 29, AC022706.1, LINC01871, and AC006033.2. We also identified numerous cancer-associated pathways whose activity was associated with GC immunity, including mTOR, PI3K-AKT, MAPK, HIF-1, and VEGF signaling pathways. Interestingly, we found seven genes (ARID1A, BCOR, MTOR, CREBBP, SPEN, NOTCH4, and TET1) whose mutations were associated with better OS in GI cancer patients receiving anti-PD-1/PD-L1 immunotherapy but were not associated with OS in GC patients without immunotherapy. The molecular features significantly associated with GC immunity could be useful biomarkers for stratifying GC patients responsive to immunotherapy or intervention targets for promoting antitumor immunity and immunotherapy response in GC.
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影响因子：
6.8
作者：
Geng, Hua;Tan, Xiao-Di
通讯作者：
Tan, Xiao-Di
影响因子：
11.2
作者：
Chajes, Veronique;Cambot, Marie;Joulin, Virginie
通讯作者：
Joulin, Virginie
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
7.3
作者：
Guri Y;Nordmann TM;Roszik J
通讯作者：
Roszik J
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y