Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer

IF 2.2 4区医学 Q2 OBSTETRICS & GYNECOLOGY Taiwanese Journal of Obstetrics & Gynecology Pub Date : 2025-01-01 DOI:10.1016/j.tjog.2024.10.002

Zhikai Xiahou , Hong Xiao , Yafeng Song , Xin Xu

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Abstract

Objective

The study aims to construct a prognostic signature to detect the molecular interaction between the fatty acid metabolism and the progression of endometrial cancer.

Materials and methods

A total of 309 fatty acid metabolism relative genes were analyzed in the endometrial cancer cohort from The Cancer Genome Atlas. Dataset GSE216872 was applied for external validation. The R program was chosen to detect the expression of FAMRGs and execute GO/KEGG analysis. Considering the clinical information and pathological features, a prognostic gene signature was constructed using LASSO Cox regression analysis. According to FAM risk score, endometrial cancer patients were divided into high and low FAM-risk score groups. By differential expression analysis and cytoscape, TEKT1 was identified as the hub gene. Functional enrichments explored the biological process TEKT1 participated. Cellular proliferation, clone formation, migration, invasion, cycle, and apoptosis were assessed to detect the effect of TEKT1 in endometrial cancer. Co-immunoprecipitation and Western blot were performed to determine the mechanism of TEKT1.

Results

A prognostic signature based on 10 FAMRGs (ACACB, PTGIS, BMPR1B, DHCR24, FAAH, GPX1, GPX4, INMT, PON3, PPT2) was generated using Lasso Cox hazards regression analysis in TCGA. TEKT1 was identified as the gene related to fatty acid metabolism. Next, we demonstrated that TEKT1 was highly expressed in endometrial cancer tissues in CPTAC and was mainly involved in the cell cycle and biosynthesis of unsaturated fatty acids. Ex-vivo experiments revealed that TEKT1 promoted proliferation, migration, and invasiveness while inhibiting apoptosis. Further experiments demonstrated that TEKT1 might promote fatty acid synthesis by binding to AMPK-γ for ACC and FASN downregulation.

Conclusion

A reliable predictive signature based on genes related to fatty acid metabolism in endometrial cancer was conducted, wherein TEKT1 was mainly implicated as the primary gene of interest. TEKT1 showed affinity to AMPK-γ and probably promoted FA synthesis in endometrial cancer.

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脂肪酸代谢相关信号提示TEKT1在子宫内膜癌中的致癌作用。

目的：构建子宫内膜癌预后标志物，检测脂肪酸代谢与子宫内膜癌进展之间的分子相互作用。材料与方法：对来自the cancer Genome Atlas的子宫内膜癌队列中309个脂肪酸代谢相关基因进行分析。使用数据集GSE216872进行外部验证。采用R程序检测FAMRGs的表达并进行GO/KEGG分析。结合临床资料和病理特征，采用LASSO Cox回归分析构建预后基因特征。根据FAM风险评分将子宫内膜癌患者分为FAM高、低风险评分组。通过差异表达分析和细胞图分析，TEKT1被确定为枢纽基因。功能富集研究了TEKT1参与的生物过程。检测TEKT1在子宫内膜癌中的增殖、克隆形成、迁移、侵袭、周期和凋亡的影响。采用免疫共沉淀法和Western blot检测TEKT1的作用机制。结果：采用Lasso Cox风险回归分析，基于10个FAMRGs （ACACB、PTGIS、BMPR1B、DHCR24、FAAH、GPX1、GPX4、INMT、PON3、PPT2）生成TCGA的预后特征。TEKT1被鉴定为脂肪酸代谢相关基因。接下来，我们证明了TEKT1在CPTAC的子宫内膜癌组织中高表达，主要参与细胞周期和不饱和脂肪酸的生物合成。离体实验显示TEKT1促进细胞增殖、迁移和侵袭性，同时抑制细胞凋亡。进一步的实验表明TEKT1可能通过与AMPK-γ结合促进ACC和FASN下调来促进脂肪酸合成。结论：基于脂肪酸代谢相关基因的子宫内膜癌预测信号可靠，其中TEKT1是主要的感兴趣基因。TEKT1与AMPK-γ有亲和力，可能促进了子宫内膜癌中FA的合成。

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来源期刊

Taiwanese Journal of Obstetrics & Gynecology OBSTETRICS & GYNECOLOGY-

CiteScore

3.60

自引率

23.80%

发文量

207

审稿时长

4-8 weeks

期刊介绍： Taiwanese Journal of Obstetrics and Gynecology is a peer-reviewed journal and open access publishing editorials, reviews, original articles, short communications, case reports, research letters, correspondence and letters to the editor in the field of obstetrics and gynecology. The aims of the journal are to: 1.Publish cutting-edge, innovative and topical research that addresses screening, diagnosis, management and care in women''s health 2.Deliver evidence-based information 3.Promote the sharing of clinical experience 4.Address women-related health promotion The journal provides comprehensive coverage of topics in obstetrics & gynecology and women''s health including maternal-fetal medicine, reproductive endocrinology/infertility, and gynecologic oncology. Taiwan Association of Obstetrics and Gynecology.