HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma.
HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma.
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HPGDS 是一种与肺腺癌脂质代谢和侵袭性相关的新型预后标志物
DOI：
10.3389/fonc.2022.894485
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发表时间：
2022
影响因子：
4.7
通讯作者：
Xie, Yajun
中科院分区：
文献类型：
--
作者：
Shao, Fengling;Mao, Huajie;Luo, Tengling;Li, Qijun;Xu, Lei;Xie, Yajun
研究背景肺腺癌（LUAD）是呼吸道最常见的恶性肿瘤，预后差.脂质代谢对肿瘤的发生、发展极为重要。然而，在LUAD的发展中，参与脂质代谢的基因的作用尚不清楚。本研究旨在明确LUAD的脂代谢异常途径，构建LUAD的预后模型，并发现新的LUAD脂代谢相关生物标志物。方法根据肿瘤基因组图谱（TCGA）中LUAD患者脂代谢相关基因的差异表达，分析LUAD患者脂代谢异常的途径。对TCGA队列（训练集）进行lasso惩罚回归分析，以构建风险评分公式。使用Kaplan-Meier分析和ROC曲线在基因表达综合（GEO）数据集（验证集）中验证风险评分的预测能力。最后，基于CRISPR基因编辑技术，敲除A549细胞系中的造血前列腺素D合酶（HPGDS），通过蛋白质印迹检测脂代谢相关标志物的变化，并通过transwell实验检测细胞迁移的变化。结果根据肺癌组织与正常组织的差异基因，发现花生四烯酸代谢途径在肺腺癌和肺鳞癌中均为异常的脂质代谢途径。基于TCGA和异常表达的脂代谢相关基因的样本信息，成功构建了9基因预后风险评分，并在GEO数据集上进行了验证。最后，我们发现A549细胞系中HPGDS的敲除促进了脂质合成，并且比对照细胞更具侵袭性。拯救试验表明，ACSL 1敲低逆转了HPGDS敲低的促迁移作用。HPGDS基因的敲低通过上调脂代谢关键酶ACSL 1和ACC的表达而促进了LUAD的迁移反应。结论脂代谢相关基因与LUAD的发生发展有关。HPGDS可能是LUAD中一个潜在的脂代谢途径的治疗靶点，而脂代谢基因在LUAD中的治疗靶点有待进一步研究。
Background Lung adenocarcinoma (LUAD) is the most common respiratory globallywith a poor prognosis. Lipid metabolism is extremely important for the occurrence and development of cancer. However, the role of genes involved in lipid metabolism in LUAD development is unclear. We aimed to identify the abnormal lipid metabolism pathway of LUAD, construct a novel prognostic model of LUAD, and discover novel biomarkers involved in lipid metabolism in LUAD. Methods Based on differentially expressed genes involved in lipid metabolism in LUAD samples from The Cancer Genome Atlas (TCGA), abnormal lipid metabolism pathways in LUAD were analyzed. The lasso penalized regression analysis was performed on the TCGA cohort (training set) to construct a risk score formula. The predictive ability of the risk score was validated in the Gene Expression Omnibus (GEO) dataset (validation set) using Kaplan-Meier analysis and ROC curves. Finally, based on CRISPR gene editing technology, hematopoietic prostaglandin D synthase (HPGDS) was knocked out in A549 cell lines, the changes in lipid metabolism-related markers were detected by western blotting, and the changes in cell migration were detected by transwell assay. Results Based on the differential genes between lung cancer tissue and normal tissue, we found that the arachidonic acid metabolism pathway is an abnormal lipid metabolism pathway in both lung adenocarcinoma and lung squamous cell carcinoma. Based on the sample information of TCGA and abnormally expressed lipid metabolism-related genes, a 9-gene prognostic risk score was successfully constructed and validated in the GEO dataset. Finally, we found that knockdown of HPGDS in A549 cell lines promoted lipid synthesis and is more invasive than in control cells. Rescue assays showed that ACSL1 knockdown reversed the pro-migration effects of HPGDS knockdown. The knockdown of HPGDS promoted migration response by upregulating the expression of the lipid metabolism key enzymes ACSL1 and ACC. Conclusion The genes involved in lipid metabolism are associated with the occurrence and development of LUAD. HPGDS can be a therapeutic target of a potential lipid metabolism pathway in LUAD, and the therapeutic target of lipid metabolism genes in LUAD should be studied further.
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影响因子：
30.8
作者：
Chung, Charles C.;Kanetsky, Peter A.;Wang, Zhaoming;Hildebrandt, Michelle A. T.;Koster, Roelof;Skotheim, Rolf I.;Kratz, Christian P.;Turnbull, Clare;Cortessis, Victoria K.;Bakken, Anne C.;Bishop, D. Timothy;Cook, Michael B.;Erickson, R. Loren;Fossa, Sophie D.;Jacobs, Kevin B.;Korde, Larissa A.;Kraggerud, Sigrid M.;Lothe, Ragnhild A.;Loud, Jennifer T.;Rahman, Nazneen;Skinner, Eila C.;Thomas, Duncan C.;Wu, Xifeng;Yeager, Meredith;Schumacher, Fredrick R.;Greene, Mark H.;Schwartz, Stephen M.;McGlynn, Katherine A.;Chanock, Stephen J.;Nathanson, Katherine L.
通讯作者：
Nathanson, Katherine L.
影响因子：
16.6
作者：
Li LY;Yang Q;Jiang YY;Yang W;Jiang Y;Li X;Hazawa M;Zhou B;Huang GW;Xu XE;Gery S;Zhang Y;Ding LW;Ho AS;Zumsteg ZS;Wang MR;Fullwood MJ;Freedland SJ;Meltzer SJ;Xu LY;Li EM;Koeffler HP;Lin DC
通讯作者：
Lin DC
DOI：
10.1186/s40880-018-0301-4
发表时间：
2018-05-21
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Cheng C;Geng F;Cheng X;Guo D
通讯作者：
Guo D
影响因子：
64.5
作者：
Kanaoka, Y;Ago, H;Hayaishi, O
通讯作者：
Hayaishi, O
影响因子：
3.3
作者：
Li X;Li X;Ding L
通讯作者：
Ding L