Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma.
Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma.
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DOI：
10.1038/s41420-022-01164-5
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发表时间：
2022-08-22
影响因子：
7
通讯作者：
Jiang, Tao
中科院分区：
文献类型：
--
作者：
Jiang, Runmin;Huan, Yu;Li, Yan;Gao, Xinyue;Sun, Qiang;Zhang, Feng;Jiang, Tao
食管癌是一种常见的恶性肿瘤，死亡率高。铜中毒是一种新型的细胞死亡，其特征在于依赖于线粒体呼吸和蛋白质脂酰化。然而，铜中毒相关基因（CRG）在ESCA中的潜在作用仍然是难以捉摸的。在这里，我们系统地评估了CRG在ESCA中的转录和遗传改变。我们确定了ESCA患者的CRGs特征。通过最小绝对收缩和选择算子（LASSO）回归分析沿着单变量考克斯回归分析和差异基因分析来构建6-CRG签名。CRGs评分可对ESCA患者的生存进行分层，CRGs评分越高，总生存率越差。此外，较高的CRG评分表明较高的病理分级和异常的细胞粘附，可能通过PI 3 K-AKT通路，这也可能是其对PI 3 K-AKT通路抑制剂敏感性增加的基础。此外，CRG高的患者往往具有更多的突变负荷和异常APOBEC突变。值得注意的是，较高的CRGs评分与更多的免疫浸润不良相关，这可以通过增加PD-L1稳定性和较高比例的旁观者T细胞来解释其恶性程度。总之，我们的报告揭示了铜中毒在ESCA中的意义，并可能在激活旁观者T细胞方面具有治疗潜力。
Esophageal carcinoma (ESCA) is a common type of cancer with high mortality. Cuproptosis is a new type of cell death and is characterized by the dependence on mitochondrial respiration and protein lipoylation. However, the potential roles of cuproptosis-related genes (CRGs) in ESCA remain elusive. Here, we systematically assessed the transcriptional and genetic alterations of CRGs in ESCA. We identified a CRGs signature for ESCA patients. A 6-CRGs signature was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis along with the univariate cox regression analysis and differential genes analysis. The CRGs score could significantly stratify ESCA patients’ survival and a high CRGs score was significantly correlated with worse overall survival. Moreover, higher CRGs score indicated higher pathology grades and aberrant cell adhesion, possibly via the PI3K-AKT pathway, which could also underly their increased sensitivity to PI3K-AKT pathway inhibitors. In addition, patients with high CRGs tend to hold more mutation load and abnormal APOBEC mutation. Notably, a higher CRGs score was anomalously associated with more immune infiltration, which could explain its malignancy by increased PD-L1 stability and a higher proportion of bystander T cells. In conclusion, our report revealed the significance of cuproptosis in ESCA and may have therapeutic potential in activating the bystander T cells.
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影响因子：
37.3
作者：
Eastlack SC;Dong S;Ivan C;Alahari SK
通讯作者：
Alahari SK
DOI：
10.1016/s1474-4422(14)70190-5
发表时间：
2015-01
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Bandmann O;Weiss KH;Kaler SG
通讯作者：
Kaler SG
影响因子：
3.5
作者：
Majumder, S.;Chatterjee, S.;Choudhuri, Soumitra Kumar
通讯作者：
Choudhuri, Soumitra Kumar
影响因子：
64.8
作者：
Simoni, Yannick;Becht, Etienne;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
5.2
作者：
Lelièvre P;Sancey L;Coll JL;Deniaud A;Busser B
通讯作者：
Busser B