Immune Infiltration and Clinical Outcome of Super-Enhancer-Associated lncRNAs in Stomach Adenocarcinoma.
Immune Infiltration and Clinical Outcome of Super-Enhancer-Associated lncRNAs in Stomach Adenocarcinoma.
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DOI：
10.3389/fonc.2022.780493
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发表时间：
2022
影响因子：
4.7
通讯作者：
Yin D
中科院分区：
文献类型：
--
作者：
Peng L;Peng JY;Cai DK;Qiu YT;Lan QS;Luo J;Yang B;Xie HT;Du ZP;Yuan XQ;Liu Y;Yin D
超级增强子（SE）由大量增强子组成，可高度增强基因表达。长非编码 RNA (lncRNA) 在胃腺癌 (STAD) 情况下往往会失调，对于平衡肿瘤免疫至关重要。然而，SE 相关的 lncRNA 是否在 STAD 的免疫浸润中发挥作用仍不清楚。在本研究中，我们在来自 11 个肿瘤组织和两个细胞系的 H3K27ac ChIP-seq 数据集中鉴定了 SE 相关的 lncRNA。通过应用六种算法（ImmuncellAI、CIBERSORT、EPIC、quantiSeq、TIMER 和 xCELL）以及免疫调节剂和趋化因子，我们发现显着失调的 SE 相关 lncRNA 与免疫细胞浸润密切相关。我们发现 SE 相关 lncRNA TM4SF1-AS1 的表达与 STAD 中 CD8+ T 细胞的比例呈负相关。 TM4SF1-AS1 抑制 T 细胞介导的免疫杀伤功能并预测对抗 PD1 治疗的免疫反应。 ChIP-seq、Hi-C 和荧光素酶检测结果证实 TM4SF1-AS1 受到其超级增强子的调节。 RNA-seq 数据显示 TM4SF1-AS1 参与免疫和癌症相关过程或途径。总之，SE 相关的 lncRNA 参与肿瘤免疫微环境，并可作为 STAD 临床结果的指标。这项研究强调了 SE 相关 lncRNA 在 STAD 免疫调节中的重要性。
Super-enhancers (SEs) comprise large clusters of enhancers that highly enhance gene expression. Long non-coding RNAs (lncRNAs) tend to be dysregulated in cases of stomach adenocarcinoma (STAD) and are vital for balancing tumor immunity. However, whether SE-associated lncRNAs play a role in the immune infiltration of STAD remains unknown. In the present study, we identified SE-associated lncRNAs in the H3K27ac ChIP-seq datasets from 11 tumor tissues and two cell lines. We found that the significantly dysregulated SE-associated lncRNAs were strongly correlated with immune cell infiltration through the application of six algorithms (ImmuncellAI, CIBERSORT, EPIC, quantiSeq, TIMER, and xCELL), as well as immunomodulators and chemokines. We found that the expression of SE-associated lncRNA TM4SF1-AS1 was negatively correlated with the proportion of CD8+ T cells present in STAD. TM4SF1-AS1 suppresses T cell-mediated immune killing function and predicts immune response to anti-PD1 therapy. ChIP-seq, Hi-C and luciferase assay results verified that TM4SF1-AS1 was regulated by its super-enhancer. RNA-seq data showed that TM4SF1-AS1 is involved in immune and cancer-related processes or pathways. In conclusion, SE-associated lncRNAs are involved in the tumor immune microenvironment and act as indicators of clinical outcomes in STAD. This study highlights the importance of SE-associated lncRNAs in the immune regulation of STAD.
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影响因子：
3.2
作者：
He C;Qi W;Wang Z
通讯作者：
Wang Z
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
30.8
作者：
Scholz, Barbara A.;Sumida, Noriyuki;Ohlsson, Rolf
通讯作者：
Ohlsson, Rolf
影响因子：
64.5
作者：
Whyte WA;Orlando DA;Hnisz D;Abraham BJ;Lin CY;Kagey MH;Rahl PB;Lee TI;Young RA
通讯作者：
Young RA
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