FADS2 (Fatty Acid Desaturase 2)

Dietary DHA supplementation improved ICB responses in lean mice. This study highlights that a microbiota-adipose axis shapes antitumor immunity, enabling potential personalized metabolic and microbial immunotherapy strategies.

Additionally, SLD regulated key signaling pathways including peroxisome proliferator-activated receptor(PPAR), tumor protein P53(P53), and Hippo. Further studies revealed that SLD activated the PPAR signaling pathway by upregulating key targets such as peroxisome proliferator-activated receptor δ(PPARδ) and fatty acid desaturase 2(FADS2) and downregulating Acyl-CoA synthetase long chain family member 3(ACSL3) and 3-hydroxy-3-methylglutaryl-CoA synthase 1(HMGCS1), which promoted fatty acid β-oxidation, inhibited fatty acid synthesis, improved hepatic lipid metabolism, and ultimately exerted the effects of protecting liver function and alleviating liver injury.

SIGNIFICANCE STATEMENT: CYP4F11 promotes non-small cell lung cancer progression by driving cell proliferation and migration, as evidenced by both loss-of-function and gain-of-function assays. Importantly, we for the first time identified a positive association between CYP4F11 and fatty acid desaturase 2, uncovering a previously unrecognized tumorigenic mechanism at the cancer-lipid metabolism interface that provides new opportunities for targeted intervention.

Firstly, the dual pathway specific enrichment strategy of O-GlcNAc modified peptides and N-glycosylated peptides was applied to ferroptosis study for the first time, which realized a systematic analysis of glycosylation patterns in the process of cell death. Secondly, high-resolution mass spectrometry combined with multi-platform data processing (MaxQuant/PEAKS) was used to deeply integrate transcriptomes and single-cell transcriptomes to construct a panoramic analysis framework with multi-omics mutual evidence. Thirdly, Scissor method was introduced to map TCGA ferroptosis pathway activity to single-cell data to achieve cross-scale analysis from population level to cell subsets. Fourth, combined with multi-dimensional bioinformatics tools, the characteristics of modification sites, subcellular localization, protein interaction network and functional pathway were annotated. Fifth, on the basis of multi-omics results, double-layer validation by qPCR and Western Blot at the transcriptional and protein levels significantly improved the credibility of the research conclusions. Its limitations are that the research mainly relies on high-throughput omics and computational analysis, and lacks systematic in vitro and in vivo functional verification and combination drug sensitivity experiments, as well as the support of real-world clinical cohorts.

Crucially, SLBP-mediated proliferation was shown to be functionally dependent on FADS2, as FADS2 inhibition abrogates SLBP-driven growth without affecting SLBP levels. Collectively, these results uncover SLBP as a multifunctional oncoprotein that promotes LUAD progression through dual mechanisms: inhibiting ferroptosis via SLC7A11 and rewiring glutamine metabolism through FADS2, offering new potential targets for therapeutic intervention.

The survival time of human BC patients with high co-expression of LMTK3 and FADS2 was shorter than that with low co-expression. These findings highlight the importance of LMTK3/FADS2 pathway in BC progression and indicate that FBC organoids might help to do comparative research and identify conserved mechanisms between HBC and FBC.

Pathway correlation and protein-protein interaction analysis indicated that the PPAR-hypoxia axis and SCD/FADS2/APOC3-HDLBP protein network are implicated in mediating the observed alterations in lipid pools and poly-unsaturation levels in pancreatic cancer under hypoxia. These results provide novel therapeutic targets in pancreatic cancer while improving our understanding of hypoxia-induced migratory potential in pancreatic cancer.

 This study reveals the causal role of omega-3 PUFAs and FADS expression in specific tissues and blood in skin diseases. These findings underscore the potential of PUFA biosynthesis pathways as therapeutic targets for skin disease interventions.

Additionally, the prognostic models comprising 62 genes was proposed and demonstrated to have remarkable predictive value. Overall, we identified a new molecular subpopulation of AML, which improved disease risk stratification and established a prognostic model for AML, which demonstrated favorable performance in retrospective validation. Since this study relies on retrospective data, further prospective analysis is required to confirm its ability to accurately reflect patient prognosis.

However, many of genetic proxies used to instrument gene expression in CD4+ T cells also act as eQTLs in other tissues, highlighting the challenges of using genetic proxies to instrument tissue-specific expression changes. We demonstrate the importance of capturing the dynamic nature of CD4+ T cells in understanding CRC risk, and prioritize genes for further investigation in cancer prevention.

Two EMT-related subtypes with distinct immune features were identified, aiding clinical decision-making. A model comprising 9 genes offers a dependable means of predicting osteosarcoma prognosis.

FADS2 was identified as a potential biomarker for predicting resistance to radiotherapy. This study is the first to examine the predictive value of lactate-related genes for radiotherapy efficacy in lung cancer, offering valuable insights for personalized treatment strategies to improve therapeutic outcomes.