Objective:To establish a prognostic model of fatty acid metabolism (FAM) for breast cancer based on FAM related genes, and to evaluate the prognosis of the FAM model. Methods: Breast cancer single-cell RNA sequencing (scRNA-seq) data set was sorted out to identify breast epithelial tumor cells, and the activation degree of breast cancer FAM in different tumor cells was obtained using area under the curve for expression level (AUCell) analysis. The weighted gene co-expression network analysis (WGCNA) was used to obtain FAM-related differential genes in breast cancer. The prognostic risk model of 767 patients was established using univariate and multivariate COX regression. Receiver operating characteristic curve (ROC), decision analysis curve (DAC) and concordance index (C-index) were used to evaluate the accuracy of the model. Finally, the GSE3143 dataset was used for validation. Results: A total of 597 differential genes were identified by single-cell transcriptomic analysis, and 12 risk-related genes associated with OS were identified by univariate and multivariate COX regression, which were FOXQ1, TFPI2, MACC1, ACOT7, MCEE, SLC27A2, QPRT, SLC2A1, ACAA1, NDRG1, KYNU and YOD1. Multi-index ROC analysis, DAC and C-index indicated that the model had high prediction accuracy. Conclusion: The prognostic model based on 12 FAM-related genes for breast cancer has certain accuracy, which could be used to guide clinical treatment more accurately.
[1] Wang XH, Ji CL, Hu JS, et al. Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway[J]. J Exp Clin Cancer Res, 2021, 40(1): 29.
[2] Wang XH, Jian W, Luo QF, et al. CircSEMA4B inhibits the progression of breast cancer by encoding a novel protein SEMA4B-211aa and regulating AKT phosphorylation[J]. Cell Death Dis, 2022, 13(9): 794.
[3] Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer[J]. Br J Cancer, 2020, 122(1): 4-22.
[4] Röhrig F, Schulze A. The multifaceted roles of fatty acid synthesis in cancer[J]. Nat Rev Cancer, 2016, 16(11): 732-749.
[5] Hoy AJ, Nagarajan SR, Butler LM. Tumour fatty acid metabolism in the context of therapy resistance and obesity[J]. Nat Rev Cancer, 2021, 21(12): 753-766.
[6] The role of the microenvironment and immune system in regulating stem cell fate in cancer - PubMed[EB/OL]. https://pubmed.ncbi.nlm.nih.gov/33509688/, 2024-03-15.
[7] Micalizzi DS, Ebright RY, Haber DA, et al. Translational regulation of cancer metastasis[J]. Cancer Res, 2021, 81(3): 517-524.
[8] Elia I, Haigis MC. Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism[J]. Nate Metab, 2021, 3(1): 21-32.
[9] Fatty acid synthesis is required for breast cancer brain metastasis - PubMed[EB/OL]. https://pubmed.ncbi.nlm.nih.gov/34179825/, 2024-03-15.
[10] Sun HD, Zhang LS, Wang ZL, et al. Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer[J]. Nat Commun, 2023, 14(1): 5590.
[11] JAK/STAT3-regulated fatty acid β-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance - PubMed[EB/OL]. https://pubmed.ncbi.nlm.nih.gov/29249690/, 2024-03-15.
[12] Hao Y, Stuart T, Kowalski MH, et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis[J]. Nat Biotechnol, 2024, 42(2): 293-304.
[13] Aran D, Looney AP, Liu L, et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage[J]. Nat Immunol, 2019, 20(2): 163-172.
[14] de Cevins C, Delage L, Batignes M, et al. Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response[J]. Cell Rep Med, 2023, 4(12): 101333.
[15] Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles[J]. Proc Natl Acad Sci USA, 2005, 102(43): 15545-15550.
[16] Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis[J]. BMC, 2008, 9: 559.
[17] Chandrashekar DS, Karthikeyan SK, Korla PK, et al. UALCAN: an update to the integrated cancer data analysis platform[J]. Neoplasia (New York, N.Y.), 2022, 25: 18-27.
[18] Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses[J]. Neoplasia, 2017, 19(8): 649-658.
[19] You MS, Xie ZL, Zhang N, et al. Signaling pathways in cancer metabolism: mechanisms and therapeutic targets[J]. Signal Transduct Target Ther, 2023, 8(1): 196.
[20] Crosstalk between metabolic reprogramming and epigenetics in cancer: updates on mechanisms and therapeutic opportunities - PubMed[EB/OL]. https://pubmed.ncbi.nlm.nih.gov/36266736/, 2024-03-15.
[21] Fedele M, Sgarra R, Battista S, et al. The epithelial-mesenchymal transition at the crossroads between metabolism and tumor progression[J]. Int J Mol Sci, 2022, 23(2): 800.
[22] Currie E, Schulze A, Zechner R, et al. Cellular fatty acid metabolism and cancer[J]. Cell Metab, 2013, 18(2): 153-161.
[23] Li YJ, Fahrmann JF, Aftabizadeh M, et al. Fatty acid oxidation protects cancer cells from apoptosis by increasing mitochondrial membrane lipids[J]. Cell Rep, 2022, 39(9): 110870.
[24] Adipocytes promote pancreatic cancer migration and invasion through fatty acid metabolic reprogramming - PubMed[EB/OL]. https://pubmed.ncbi.nlm.nih.gov/37264956/, 2024-03-15.
[25] An Q, Lin R, Wang DM, et al. Emerging roles of fatty acid metabolism in cancer and their targeted drug development[J]. Eur J Med Chem, 2022, 240: 114613.
[26] Kang HM, Ahn SH, Choi P, et al. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development[J]. Nat Med, 2015, 21(1): 37-46.
[27] Tcheng M, Roma A, Ahmed N, et al. Very long chain fatty acid metabolism is required in acute myeloid leukemia[J]. Blood, 2021,137(25): 3518-3532
[28] Kelly CJ, Zheng L, Campbell EL, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial hif augments tissue barrier function[J]. Cell Host Microbe, 2015, 17(5): 662-671.
[29] Mao Z, Feng MJ, Li ZR, et al. ETV5 regulates hepatic fatty acid metabolism through PPAR signaling pathway[J]. Diabetes, 2021, 70(1): 214-226.
[30] Kwong SC, Jamil AHA, Rhodes A, et al. Metabolic role of fatty acid binding protein 7 in mediating triple-negative breast cancer cell death via PPAR-α Signaling[J]. J Lipid Res, 2019, 60(11): 1807-1817.
[31] Zheng C, Zhang GC, Xie K, et al. Pan-cancer analysis and experimental validation identify acot7 as a novel oncogene and potential therapeutic target in lung adenocarcinoma[J]. Cancers, 2022, 14(18): 4522.
[32] Jung SH, Lee HC, Hwang HJ, et al. Acyl-CoA thioesterase 7 is involved in cell cycle progression via regulation of PKCζ-P53-P21 signaling pathway[J]. Cell Death Dis, 2017, 8(5): e2793.
[33] GRP94 is involved in the lipid phenotype of brain metastatic cells - PubMed[EB/OL]. https://pubmed.ncbi.nlm.nih.gov/31395819/, 2024-03-15.
