Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer

Abnormal lipid metabolism often occurs under hypoxic microenvironment, which is an important energy supplement for cancer cell proliferation and metastasis. We aimed to explore the lipid metabolism characteristics and gene expression features of pancreatic ductal adenocarcinoma (PDAC) related to hyp...

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Main Authors: Yaning Li, Xinyue Liang, Gang Che, Yutong Chen, Lisi Luo, Kecheng Liu, Rongzhi Xie, Linjuan Zeng
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/12/10/1533
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author Yaning Li
Xinyue Liang
Gang Che
Yutong Chen
Lisi Luo
Kecheng Liu
Rongzhi Xie
Linjuan Zeng
author_facet Yaning Li
Xinyue Liang
Gang Che
Yutong Chen
Lisi Luo
Kecheng Liu
Rongzhi Xie
Linjuan Zeng
author_sort Yaning Li
collection DOAJ
description Abnormal lipid metabolism often occurs under hypoxic microenvironment, which is an important energy supplement for cancer cell proliferation and metastasis. We aimed to explore the lipid metabolism characteristics and gene expression features of pancreatic ductal adenocarcinoma (PDAC) related to hypoxia and identify biomarkers for molecular classification based on hypoxic lipid metabolism that are evaluable for PDAC prognosis and therapy. The multiple datasets were analyzed integratively, including corresponding clinical information of samples. PDAC possesses a distinct metabolic profile and oxygen level compared with normal pancreatic tissues, according to the bioinformatics methods. In addition, a study on untargeted metabolomics using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry(UPLC-MS) revealed lipid metabolites differences affected by oxygen. Analysis of PDAC gene expression profiling in The Cancer Genome Atlas (TCGA) revealed that the sphingolipid process correlates closely with HIF1α. According to the characters of HIF-1 and sphingolipid, samples can be clustered into three subgroups using non-negative matrix factorization clustering. In cluster2, patients had an increased survival time. Relatively high MUC16 mutation arises in cluster2 and may positively influence the cancer survival rates. This study explored the expression pattern of lipid metabolism under hypoxia microenvironment in PDAC. On the basis of metabolic signatures, we identified the prognosis subtypes linking lipid metabolism to hypoxia. The classifications may be conducive to developing personalized treatment programs targeting metabolic profiles.
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spelling doaj.art-1aad57d16e994a918db34dbef39f36ee2023-11-23T23:10:12ZengMDPI AGBiomolecules2218-273X2022-10-011210153310.3390/biom12101533Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic CancerYaning Li0Xinyue Liang1Gang Che2Yutong Chen3Lisi Luo4Kecheng Liu5Rongzhi Xie6Linjuan Zeng7Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaDepartment of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaDepartment of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaDepartment of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaDepartment of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaDepartment of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaDepartment of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaDepartment of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, ChinaAbnormal lipid metabolism often occurs under hypoxic microenvironment, which is an important energy supplement for cancer cell proliferation and metastasis. We aimed to explore the lipid metabolism characteristics and gene expression features of pancreatic ductal adenocarcinoma (PDAC) related to hypoxia and identify biomarkers for molecular classification based on hypoxic lipid metabolism that are evaluable for PDAC prognosis and therapy. The multiple datasets were analyzed integratively, including corresponding clinical information of samples. PDAC possesses a distinct metabolic profile and oxygen level compared with normal pancreatic tissues, according to the bioinformatics methods. In addition, a study on untargeted metabolomics using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry(UPLC-MS) revealed lipid metabolites differences affected by oxygen. Analysis of PDAC gene expression profiling in The Cancer Genome Atlas (TCGA) revealed that the sphingolipid process correlates closely with HIF1α. According to the characters of HIF-1 and sphingolipid, samples can be clustered into three subgroups using non-negative matrix factorization clustering. In cluster2, patients had an increased survival time. Relatively high MUC16 mutation arises in cluster2 and may positively influence the cancer survival rates. This study explored the expression pattern of lipid metabolism under hypoxia microenvironment in PDAC. On the basis of metabolic signatures, we identified the prognosis subtypes linking lipid metabolism to hypoxia. The classifications may be conducive to developing personalized treatment programs targeting metabolic profiles.https://www.mdpi.com/2218-273X/12/10/1533pancreatic cancerHIF-1αhypoxia lipid metabolismsphingolipid
spellingShingle Yaning Li
Xinyue Liang
Gang Che
Yutong Chen
Lisi Luo
Kecheng Liu
Rongzhi Xie
Linjuan Zeng
Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer
Biomolecules
pancreatic cancer
HIF-1α
hypoxia lipid metabolism
sphingolipid
title Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer
title_full Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer
title_fullStr Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer
title_full_unstemmed Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer
title_short Molecular Classification of Genes Associated with Hypoxic Lipid Metabolism in Pancreatic Cancer
title_sort molecular classification of genes associated with hypoxic lipid metabolism in pancreatic cancer
topic pancreatic cancer
HIF-1α
hypoxia lipid metabolism
sphingolipid
url https://www.mdpi.com/2218-273X/12/10/1533
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