Multi-Omics Profiling Reveals Glycerolipid Metabolism-Associated Molecular Subtypes and Identifies ALDH2 as a Prognostic Biomarker in Pancreatic Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Scheme
2.2. Pan-Cancer Analysis of GMRGs
2.3. scRNA-seq and Spatial Transcriptome Data Analysis
2.4. Lipidomic Analysis for Serum Samples in PC Patients
2.5. Identification of GLM-Related Molecular Subtypes in PC
2.6. Analysis of TIME and Drug Sensitivity Based on GLM-Related Molecular Subtypes
2.7. Identification of the Core GMRG in PC
2.8. Real-Time Quantitative PCR of PC Cell Lines and Tissue Samples
2.9. Immunohistochemical Analysis of ALDH2 Expression and Its Correlation with Clinicopathologic Features in PC
3. Results
3.1. Pan-Cancer Characterization of GMRGs
3.2. scRNA-seq Data Revealed the Presence of Aberrant GLM in PC
3.3. Characterization of GLM in PC Based on Lipidomic Analysis
3.4. Development of GLM-Related Molecular Subtypes Based on Bulk RNA-seq
3.5. Differences in TIME Between Different Subtypes
3.6. GLM-Related Molecular Subtypes Can Guide Personalized Therapy for PC
3.7. Identification and Validation of the Prognostic Target in PC
3.8. The Expression of ALDH2 and Its Association with Clinicopathological Parameters in PC
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviation
ACC | Adrenocortical carcinoma |
BLCA | Bladder urothelial carcinoma |
BRCA | Breast invasive carcinoma |
CESC | Cervical squamous cell carcinoma and endocervical adenocarcinoma |
CHOL | Cholangiocarcinoma |
COAD | Colon adenocarcinoma |
DLBC | Lymphoid neoplasm diffuse large B-cell lymphoma |
ESCA | Esophageal carcinoma |
GBM | Glioblastoma multiforme |
HNSC | Head and neck squamous cell carcinoma |
KICH | Kidney chromophobe |
KIRC | Kidney renal clear cell carcinoma |
KIRP | Kidney renal papillary cell carcinoma |
LGG | Brain lower-grade glioma |
LIHC | Liver hepatocellular carcinoma |
LUAD | Lung adenocarcinoma |
LUSC | Lung squamous cell carcinoma |
MESO | Mesothelioma |
OV | Ovarian serous cystadenocarcinoma |
PAAD | Pancreatic adenocarcinoma |
PCPG | Pheochromocytoma and paraganglioma |
PRAD | Prostate adenocarcinoma |
READ | Rectum adenocarcinoma |
SARC | Sarcoma |
SKCM | Skin cutaneous melanoma |
STAD | Stomach adenocarcinoma |
TGCT | Testicular germ cell tumors |
THYM | Thymoma |
THCA | Thyroid carcinoma |
UCS | Uterine carcinosarcoma |
UCEC | Uterine corpus endometrial carcinoma |
UVM | Uveal melanoma |
GLM | Glycerolipid metabolism |
PC | Pancreatic cancer |
GMRG | Glycerolipid metabolism-related gene |
CNV | Copy number variants |
SNV | Single nucleotide variations |
scRNA-seq | Single-cell RNA sequencing |
TAG | Triacylglycerol |
DAG | Diacylglycerol |
MAG | Monoacylglycerol |
TIME | Tumor immune microenvironment |
RF | Random forest |
QC | Quality control |
NMF | Nonnegative matrix factorization |
ssGSEA | Single sample gene set enrichment analysis |
ICG | Immune checkpoint gene |
t-SNE | t-Stochastic Neighbor Embedding |
OS | Overall survival |
RFS | Recurrence-free survival |
ALDH2 | Aldehyde dehydrogenase 2 |
ALDH3A2 | Aldehyde dehydrogenase 3 family member A2 |
ALDH9A1 | Aldehyde dehydrogenase 9A1 |
DGKB | Diacylglycerol kinase beta |
DGKH | Diacylglycerol kinase eta |
DGKI | Diacylglycerol kinase iota |
AGK | Acylglycerol kinase |
AKR1B1 | Aldo-keto reductase family 1 member B1 |
GLYCTK | Glycerate kinase |
LPL | Lipoprotein lipase |
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Liu, J.; Ma, S.; Deng, D.; Yang, Y.; Li, J.; Zhang, Y.; Yin, P.; Shang, D. Multi-Omics Profiling Reveals Glycerolipid Metabolism-Associated Molecular Subtypes and Identifies ALDH2 as a Prognostic Biomarker in Pancreatic Cancer. Metabolites 2025, 15, 207. https://doi.org/10.3390/metabo15030207
Liu J, Ma S, Deng D, Yang Y, Li J, Zhang Y, Yin P, Shang D. Multi-Omics Profiling Reveals Glycerolipid Metabolism-Associated Molecular Subtypes and Identifies ALDH2 as a Prognostic Biomarker in Pancreatic Cancer. Metabolites. 2025; 15(3):207. https://doi.org/10.3390/metabo15030207
Chicago/Turabian StyleLiu, Jifeng, Shurong Ma, Dawei Deng, Yao Yang, Junchen Li, Yunshu Zhang, Peiyuan Yin, and Dong Shang. 2025. "Multi-Omics Profiling Reveals Glycerolipid Metabolism-Associated Molecular Subtypes and Identifies ALDH2 as a Prognostic Biomarker in Pancreatic Cancer" Metabolites 15, no. 3: 207. https://doi.org/10.3390/metabo15030207
APA StyleLiu, J., Ma, S., Deng, D., Yang, Y., Li, J., Zhang, Y., Yin, P., & Shang, D. (2025). Multi-Omics Profiling Reveals Glycerolipid Metabolism-Associated Molecular Subtypes and Identifies ALDH2 as a Prognostic Biomarker in Pancreatic Cancer. Metabolites, 15(3), 207. https://doi.org/10.3390/metabo15030207