Pan-Cancer Analysis Reveals Distinct Metabolic Reprogramming in Different Epithelial-Mesenchymal Transition Activity States.
Pan-Cancer Analysis Reveals Distinct Metabolic Reprogramming in Different Epithelial-Mesenchymal Transition Activity States.
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泛癌分析揭示了在不同的上皮-间充质转化活动状态下不同的代谢重编程。
DOI：
10.3390/cancers13081778
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发表时间：
2021-04-08
期刊：
影响因子：
5.2
通讯作者：
Cheong JH
中科院分区：
文献类型：
--
作者：
Sung JY;Cheong JH
最近的肿瘤基因组分类表明，临床难治性肿瘤聚集为与上皮-间充质转化(EMT)相关的一个独特的分子亚型。EMT亚型肿瘤具有共同的恶性特征，如预后不良和转移，临床上难以治愈，并且对化疗和免疫检查点阻断具有抵抗力。因此，临床上迫切需要确定该肿瘤亚型的潜在治疗靶点。在这里，我们基于EMT活性对31种癌症类型的9452个样本的代谢特征进行了分析，发现约80%到90%的癌症类型具有与高EMT状态相关的高碳水化合物和能量代谢。此外，我们将CHST14确定为与能量代谢重编程相关的胃癌EMT亚型的潜在代谢靶点。我们的分析确定了与EMT相关的代谢重编程，建议临床难治性癌症亚型的代谢相关靶点。上皮-间充质转化(EMT)在肿瘤的发生、侵袭和转移中起着至关重要的作用。它的活性影响代谢重新编程、肿瘤侵袭性和患者生存。肿瘤代谢异常已被确定为癌症的标志，并被认为是潜在的治疗靶点。我们使用来自癌症基因组图谱的31种不同癌症类型的9452个转录本的数据，通过EMT活性来描述不同的代谢特征。我们的结果表明，~80%到90%的癌症类型具有高碳水化合物和能量代谢，这与高EMT组有关。值得注意的是，在不同的EMT活动中，不同免疫微环境中的代谢重编程与患者预后相关。EMT活性高的9种癌症患者的存活率有显著差异。胃癌表现出能量代谢升高，与不良预后相关(p<；0.0068)，再加上CHST14的高表达，表明它可能是一个潜在的药物靶点。我们的分析强调了癌症类型依赖的EMT和代谢重编程活动的盛行，并确定了可能作为潜在治疗靶点的代谢相关基因。
Recent genomic classification of tumors has stated that clinically refractory cancers aggregate as a distinct molecular subtype associated with epithelial–mesenchymal transition (EMT). EMT subtype tumors are clinically intractable due to shared malignant characteristics such as poor prognosis and metastasis and are resistant to chemotherapy and immune checkpoint blockades. Therefore, there is an urgent clinical need for the identification of potential therapeutic targets for this tumor subtype. Here, we profiled the metabolic signatures of 9452 samples across 31 cancer types based on EMT activity and identified that ~80 to 90% of cancer types had high carbohydrate and energy metabolism associated with the high EMT state. Furthermore, we identified CHST14 as a potential metabolic target for the EMT subtype for stomach cancer associated with reprogramming of energy metabolism. Our analyses identified metabolic reprogramming associated with EMT, suggesting metabolism-associated targets for clinically refractory cancer subtypes. Epithelial–mesenchymal transition (EMT) is critical for cancer development, invasion, and metastasis. Its activity influences metabolic reprogramming, tumor aggressiveness, and patient survival. Abnormal tumor metabolism has been identified as a cancer hallmark and is considered a potential therapeutic target. We profiled distinct metabolic signatures by EMT activity using data from 9452 transcriptomes across 31 different cancer types from The Cancer Genome Atlas. Our results demonstrated that ~80 to 90% of cancer types had high carbohydrate and energy metabolism, which were associated with the high EMT group. Notably, among the distinct EMT activities, metabolic reprogramming in different immune microenvironments was correlated with patient prognosis. Nine cancer types showed a significant difference in survival with the presence of high EMT activity. Stomach cancer showed elevated energy metabolism and was associated with an unfavorable prognosis (p < 0.0068) coupled with high expression of CHST14, indicating that it may serve as a potential drug target. Our analyses highlight the prevalence of cancer type-dependent EMT and metabolic reprogramming activities and identified metabolism-associated genes that may serve as potential therapeutic targets.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
4.4
作者：
Lee BK;Tiong KH;Chang JK;Liew CS;Abdul Rahman ZA;Tan AC;Khang TF;Cheong SC
通讯作者：
Cheong SC
DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
影响因子：
16.6
作者：
Oh SC;Sohn BH;Cheong JH;Kim SB;Lee JE;Park KC;Lee SH;Park JL;Park YY;Lee HS;Jang HJ;Park ES;Kim SC;Heo J;Chu IS;Jang YJ;Mok YJ;Jung W;Kim BH;Kim A;Cho JY;Lim JY;Hayashi Y;Song S;Elimova E;Estralla JS;Lee JH;Bhutani MS;Lu Y;Liu W;Lee J;Kang WK;Kim S;Noh SH;Mills GB;Kim SY;Ajani JA;Lee JS
通讯作者：
Lee JS
影响因子：
51.1
作者：
Cheong, Jae-Ho;Yang, Han-Kwang;Noh, Sung Hoon
通讯作者：
Noh, Sung Hoon