LMO3 downregulation in PCa: A prospective biomarker associated with immune infiltration

Xu, Wenchao; Sun, Taotao; Wang, Jiaxin; Li, Hao; Chen, Bingliang; Zhou, Yingjian; Wang, Tao; Wang, Shaogang; Liu, Jihong; Jiang, Hongyang

doi:10.3389/fgene.2022.945151

Cited by 4 publications

(2 citation statements)

References 44 publications

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“…Previous studies in PDAC and prostate cancer have suggested that LMO3 may exert suppressive effects on tumorigenesis in these cancers 43,44 . Furthermore, LMO3 may be involved in metabolic reprogramming 45 and has been identified as a master regulator of adipogenesis 24 .…”

Section: Lim Domain Only (Lmo) Proteins Constitute a Family Of Transc...mentioning

confidence: 97%

LMO3 is a suppressor of the basal-like/squamous PDAC subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism

Ohara,

Craig,

Liu

et al. 2023

Preprint

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Pancreatic ductal adenocarcinoma (PDAC) encompasses diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, each exhibiting distinct characteristics, with the latter known for its aggressiveness. We employed an integrative approach combining transcriptomic and metabolomic analyses to pinpoint potential genes contributing to the basal-like/squamous subtype differentiation. Applying this approach to our NCI-UMD-German and a validation cohort, we identified LIM Domain Only 3 (LMO3), a transcription co-factor, as a candidate suppressor of the basal-like/squamous subtype. Reduced LMO3 expression was significantly associated with higher pathological grade, advanced disease stage, induction of the basal-like/squamous subtype, and decreased survival among PDAC patients.In vitroexperiments demonstrated thatLMO3transgene expression inhibited PDAC cell proliferation and migration/invasion, concurrently downregulating the basal-like/squamous gene signature. Metabolomic analysis of patient tumors and PDAC cells revealed a metabolic program linked to elevated LMO3 expression and the classical/progenitor subtype, characterized by enhanced lipogenesis and suppressed amino acid metabolism. Notably, glycerol 3-phosphate (G3P) levels positively correlated with LMO3 expression and associated with improved patient survival. Furthermore, glycerol-3-phosphate dehydrogenase 1 (GPD1), a crucial enzyme in G3P synthesis, showed upregulation in LMO3-high and classical/progenitor PDAC, suggesting its potential role in mitigating disease aggressiveness. Collectively, our findings suggest that heightened LMO3 expression reduces transcriptomic and metabolomic characteristics indicative of basal-like/squamous tumors with decreased disease aggressiveness in PDAC patients. The observations describe LMO3 as a candidate for diagnostic and therapeutic targeting in PDAC.Graphical abstractHighlightsLMO3 is downregulated in basal-like/squamous PDAC while its expression is maintained in the classical/progenitor PDAC subtypeUpregulated LMO3 expression correlates with improved PDAC survival and reduced proliferation and migration/invasion in PDAC cellsUpregulated LMO3 suppresses basal-like/squamous differentiation and induces a unique metabolic signature characterized by elevated lipogenesis and diminished amino acid metabolism, resembling the classical/progenitor PDAC subtypeEnhanced LMO3 expression associates with elevated glycerol 3-phosphate levels in PDAC, correlating with improved patient survival in PDAC

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Section: Lim Domain Only (Lmo) Proteins Constitute a Family Of Transc...mentioning

confidence: 97%

LMO3 is a suppressor of the basal-like/squamous PDAC subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism

Ohara,

Craig,

Liu

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Despite improvements in clinical diagnosis and surgical techniques, chemotherapy resistance and metastasis are major challenges in improving the prognosis of malignant GC ( 24 ). Therefore, identifying effective prognostic biomarkers and targets associated with immunological interventions is a GC research hotspot ( 8 , 25 ). Under hypoxic conditions, tumor cells require large amounts of metabolites and nutrients to meet their high metabolic energy demand ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Prediction and verification of the prognostic biomarker SLC2A2 and its association with immune infiltration in gastric cancer

Zhang,

Zhou,

Song

et al. 2023

Oncol Lett

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Gastric cancer (GC) is the fifth most common cause of cancer-associated deaths; however, its treatment options are limited. Despite clinical improvements, chemotherapy resistance and metastasis are major challenges in improving the prognosis and quality of life of patients with GC. Therefore, effective prognostic biomarkers and targets associated with immunological interventions need to be identified. Solute carrier family 2 member 2 ( SLC2A2 ) may serve a role in tumor development and invasion. The present study aimed to evaluate SLC2A2 as a prospective prognostic marker and chemotherapeutic target for GC. SLC2A2 expression in several types of cancer and GC was analyzed using online databases, and the effects of SLC2A2 expression on survival prognosis in GC were investigated. Clinicopathological parameters were examined to explore the association between SLC2A2 expression and overall survival (OS). Associations between SLC2A2 expression and immune infiltration, immune checkpoints and IC 50 were estimated using quantification of the tumor immune contexture from human RNA-seq data, the Tumor Immune Estimation Resource 2.0 database and the Genomics of Drug Sensitivity in Cancer database. Differential SLC2A2 expression and the predictive value were validated using the Human Protein Atlas, Gene Expression Omnibus, immunohistochemistry and reverse transcription-quantitative PCR. SLC2A2 expression was downregulated in most types of tumor but upregulated in GC. Functional enrichment analysis revealed an association between SLC2A2 expression and lipid metabolism and the tumor immune microenvironment. According to Gene Ontology term functional enrichment analysis, SLC2A2 -related differentially expressed genes were enriched predominantly in ‘chylomicron assembly’, ‘plasma lipoprotein particle assembly’, ‘high-density lipoprotein particle’, ‘chylomicron’, ‘triglyceride-rich plasma lipoprotein particle’, ‘very-low-density lipoprotein particle’. ‘intermembrane lipid transfer activity’, ‘lipoprotein particle receptor binding’, ‘cholesterol transporter activity’ and ‘intermembrane cholesterol transfer activity’. In addition, ‘cholesterol metabolism’, and ‘fat digestion and absorption’ were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Patients with GC with high SLC2A2 expression had higher levels of neutrophil and M2 macrophage infiltration and a significant inverse correlation was observed between SLC2A2 expression and MYC targets, tumor mutation burden, microsatellite instability and immune checkpoints. Furthermore, patients with high SLC2A2 expression had worse prognosis, including OS, disease-specific survival and progression-free interval. Multivariate regres...

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A Novel Signature Based on Anoikis Associated with BCR-Free Survival for Prostate Cancer

2023

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LMO3 downregulation in PCa: A prospective biomarker associated with immune infiltration

Cited by 4 publications

References 44 publications

LMO3 is a suppressor of the basal-like/squamous PDAC subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism

LMO3 is a suppressor of the basal-like/squamous PDAC subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism

Prediction and verification of the prognostic biomarker SLC2A2 and its association with immune infiltration in gastric cancer

A Novel Signature Based on Anoikis Associated with BCR-Free Survival for Prostate Cancer

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