ACACB is a novel metabolism-related biomarker in the prediction of response to cetuximab therapy inmetastatic colorectal cancer.
ACACB is a novel metabolism-related biomarker in the prediction of response to cetuximab therapy inmetastatic colorectal cancer.
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AACCB 是一种新型代谢相关生物标志物，可预测转移性结直肠癌对西妥昔单抗治疗的反应
DOI：
10.3724/abbs.2022121
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发表时间：
2022-09-25
影响因子：
3.7
通讯作者：
Zheng M
中科院分区：
文献类型：
--
作者：
Hong HJ;Shao Y;Zhang S;Yang G;Jia H;Yang X;Huang L;Li S;Aikemu B;Zhang L;Ma J;Zang L;Sun J;Zheng M
西妥昔单抗是治疗转移性结直肠癌最有价值的靶向治疗单抗之一。然而，在结直肠癌治疗中影响西妥昔单抗耐药性的机制仍不清楚。代谢，尤其是脂肪酸代谢在肿瘤治疗中起着重要的作用。西妥昔单抗耐药与代谢的相关性以及是否可以作为评价西妥昔单抗对结直肠癌治疗敏感性的新的生物标志物仍需进一步探讨。本研究通过对西妥昔单抗耐药与脂肪酸代谢关系的综合分析，利用生物信息学技术筛选出与西妥昔单抗耐药相关的差异表达基因。我们发现乙酰辅酶A羧基酶β(ACACB)、ADH1C、CES1、MGLL、FMO5和GPT是中枢基因，其中ACACB是最重要的生物标志物。此外，我们通过生物信息学技术、体外实验和临床队列验证，系统地分析了ACACB在结直肠癌发生中的作用，包括组织表达、结直肠癌细胞生长、西妥昔单抗敏感性和潜在的下游通路。我们的结果证实了西妥昔单抗耐药与代谢有关。ACACB可降低大肠癌患者对西妥昔单抗的敏感性，其机制可能与EGFR磷酸化有关，可影响mTOR/Akt信号通路的激活，调节CDT1、细胞周期蛋白D1和p21相关的细胞周期调控。
Cetuximab is one of the most valuable targeted therapy monoclonal antibodies in the treatment of metastatic colorectal cancer (CRC). However, the mechanisms affecting cetuximab resistance in CRC treatment remain unclear. Metabolism, especially fatty acid metabolism, has been reported to play an important role in tumor treatment. The correlation between cetuximab resistance and metabolism and whether it can be a new biomarker to evaluate the sensitivity of cetuximab in CRC treatment still need to be further explored. In this study, we perform a comprehensive analysis to confirm the relationship between fatty acid metabolism and cetuximab resistance, and the differentially expressed genes (DEGs) related to cetuximab drug resistance in CRC are screened by bioinformatics technology. We find that acetyl-CoA carboxylase beta (ACACB), ADH1C, CES1, MGLL, FMO5, and GPT are the hub DEGs, and ACACB is the most important biomarker among them. In addition, we systematically analyze the role of ACACB in the tumorigenesis of CRC, including tissue expression, CRC cell growth, cetuximab sensitivity, and potential downstream pathways, by using bioinformatics techniques, in vitro experiments and clinical cohort validation. Our results confirm that cetuximab resistance is correlated with metabolism. ACACB can lead to decreased sensitivity to cetuximab in CRC, and its mechanism may be related to EGFR phosphorylation, which could affect the activation of the mTOR/Akt signaling pathway and regulation of CDT1-, cyclin D1-, and p21-related cell cycle modulation.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
3.8
作者：
Harada K;Ferdous T;Cui D;Kuramitsu Y;Matsumoto T;Ikeda E;Okano H;Ueyama Y
通讯作者：
Ueyama Y
DOI：
10.1016/s0140-6736(17)33326-3
发表时间：
2018-03-17
期刊：
Lancet (London, England)
影响因子：
--
作者：
Allemani C;Matsuda T;Di Carlo V;Harewood R;Matz M;Nikšić M;Bonaventure A;Valkov M;Johnson CJ;Estève J;Ogunbiyi OJ;Azevedo E Silva G;Chen WQ;Eser S;Engholm G;Stiller CA;Monnereau A;Woods RR;Visser O;Lim GH;Aitken J;Weir HK;Coleman MP;CONCORD Working Group
通讯作者：
CONCORD Working Group
影响因子：
3.7
作者：
Liang, Hongguang;Lin, Zelong;Zeng, Lixian
通讯作者：
Zeng, Lixian
影响因子：
8
作者：
Luwor, RB;Lu, Y;Fan, Z
通讯作者：
Fan, Z