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

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 fro...

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Main Authors: Zhikai Xiahou, Hong Xiao, Yafeng Song, Xin Xu
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Taiwanese Journal of Obstetrics & Gynecology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1028455924002833
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author Zhikai Xiahou
Hong Xiao
Yafeng Song
Xin Xu
author_facet Zhikai Xiahou
Hong Xiao
Yafeng Song
Xin Xu
author_sort Zhikai Xiahou
collection DOAJ
description 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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spelling doaj-art-76d29d9ae9ea4feeae2d66f75c1c35ad2025-01-09T06:12:51ZengElsevierTaiwanese Journal of Obstetrics & Gynecology1028-45592025-01-0164192104Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancerZhikai Xiahou0Hong Xiao1Yafeng Song2Xin Xu3School of Sport Science, Beijing Sport University, Beijing, ChinaPhysical Education Department, Northeastern University, Shenyang, ChinaSchool of Sport Science, Beijing Sport University, Beijing, ChinaDepartment of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1028455924002833Fatty acid metabolismTEKT1AMPKPrognostic signatureEndometrial cancer
spellingShingle Zhikai Xiahou
Hong Xiao
Yafeng Song
Xin Xu
Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer
Taiwanese Journal of Obstetrics & Gynecology
Fatty acid metabolism
TEKT1
AMPK
Prognostic signature
Endometrial cancer
title Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer
title_full Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer
title_fullStr Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer
title_full_unstemmed Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer
title_short Fatty acid metabolism-related signature suggests an oncogenic role of TEKT1 in endometrial cancer
title_sort fatty acid metabolism related signature suggests an oncogenic role of tekt1 in endometrial cancer
topic Fatty acid metabolism
TEKT1
AMPK
Prognostic signature
Endometrial cancer
url http://www.sciencedirect.com/science/article/pii/S1028455924002833
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AT hongxiao fattyacidmetabolismrelatedsignaturesuggestsanoncogenicroleoftekt1inendometrialcancer
AT yafengsong fattyacidmetabolismrelatedsignaturesuggestsanoncogenicroleoftekt1inendometrialcancer
AT xinxu fattyacidmetabolismrelatedsignaturesuggestsanoncogenicroleoftekt1inendometrialcancer