Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma

Li, Hui; Wang, Xian-ling; Tang, Jun; Zhao, Haibo; Duan, Min

doi:10.3892/ol.2019.10974

Cited by 7 publications

(9 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ELOVL5 has been shown to be markedly upregulated in prostate carcinoma cells and its inhibition has been detrimental to prostate cancer cell survival [52]. The status of ELOVL6 in cancer is less clear, as both increased and decreased expression have been reported to correlate negatively with cancer progression and patient survival in breast or liver cancer [53][54][55]. The downregulation of ELOVL6 observed in our study corresponded with the lack of upregulation of stearic acid, which is a major product of this enzyme [56,57].…”

Section: Discussionsupporting

confidence: 48%

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Hofmanová

Slavík

Cigánek

et al. 2021

IJMS

View full text Add to dashboard Cite

The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM+ cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.

show abstract

Section: Discussionsupporting

confidence: 48%

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Hofmanová

Slavík

Cigánek

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Finally, the pressing need for optimized energetic pathways facing nutrient shortage drives enhanced glucose uptake ( SLC2A3/GLUT3) 47,48 and lipid catabolism ( RORA, ANGPTL4) 49,50 . The later includes the upregulation of carnitine transporters ( SLC22A15) 51 , while counteracting lipogenesis ( ELOVL6) through rate limiting enzymes downregulation 52 and promotion of autophagic events ( DDIT4, HK2, PFKFB3, DEPP1 ) 53–56 . Significantly differentially expressed genes were then clustered by gene ontology and the enrichment of gene ontology terms was tested using Fisher’s exact test ( Figure 2D ).…”

Section: Resultsmentioning

confidence: 99%

Metabolomics, Transcriptomics and Functional Glycomics Reveals Bladder Cancer Cells Plasticity and Enhanced Aggressiveness Facing Hypoxia and Glucose Deprivation

Peixoto

Freitas

Ferreira

et al. 2021

Preprint

View full text Add to dashboard Cite

Bladder cancer constitutes one of the deadliest genitourinary diseases, especially when diagnosed at late stages. These tumours harbour microenvironmental niches characterized by low levels of oxygen (hypoxia) and limited glucose supply due to poor vascularization. However, the synergic contribution of these features to disease development is poorly understood. Here, we demonstrated that cells with distinct histopathological and molecular backgrounds responded similarly to such stimuli. Cancer cells arrested proliferation, significantly increased invasive capacity in vitro and enhanced tolerance to cisplatin-based chemotherapy. Reoxygenation and access to glucose restored basal proliferation and invasion levels without triggering stress-induced apoptosis, denoting significant cellular plasticity in adapting to microenvironmental cues. Whole transcriptomics showed major molecular reprogramming, supporting main functional alterations. Metabolomics evidenced fatty acids β-oxidation as main bioenergetic pathway rather than anaerobic glycolysis generally adopted by hypoxic cells. Joint pathway analysis also suggested relevant alterations in mucin-type O-glycan biosynthesis. Glycomics confirmed a major antagonization of O-glycosylation pathways, leading to simple cell glycophenotypes characterized by the accumulation of immature short-chain O-glycans such as Tn and STn antigens at the cell surface. Glycoengineered models reflecting simple cell glycophenotypes were developed and functional studies in vitro and in vivo showed that Tn and STn overexpression decreased proliferation and promoted chemoresistance, reinforcing their close link with tumour aggressiveness. Collectively, we have demonstrated that hypoxia and glucose deprivation trigger more aggressive cell behaviours, in what appears to be an escape mechanism from microenvironmental stress. We propose that, altered glycosylation may be used to target these subpopulations, paving the way for precision oncology.

show abstract

“…Knockdown of ELOVL6 expression inhibited hepatocellular carcinoma cell proliferation in vitro and in vivo (33). Meanwhile, a positive correlation was observed between high ELOVL6 expression and the survival of patients with hepatocellular carcinoma (37). Our IHC results showed that the expression of ELOVL6 was low in the tissues of patients with COAD.…”

Section: Discussionmentioning

confidence: 58%

A novel enterocyte-related 4-gene signature for predicting prognosis in colon adenocarcinoma

Cheng

Wei²,

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundColon adenocarcinoma (COAD) is a fatal disease, and its cases are constantly increasing worldwide. Further, the therapeutic and management strategies for patients with COAD are still unsatisfactory due to the lack of accurate patient classification and prognostic models. Therefore, our study aims to identify prognostic markers in patients with COAD and construct a cell subtype-specific prognostic model with high accuracy and robustness.MethodsSingle-cell transcriptomic data of six samples were retrieved from the Gene expression omnibus (GEO) database. The cluster annotation and cell-cell communication analysis identified enterocytes as a key player mediating signal communication networks. A four-gene signature prognostic model was constructed based on the enterocyte-related differentially expressed genes (ERDEGs) in patients with COAD of the Cancer Genome Atlas cohort. The prognostic model was validated on three external validation cohorts from the GEO database. The correlation between immune cell infiltration, immunotherapy response, drug sensitivity, and the four-gene signature prognostic model was investigated. Finally, immunohistochemistry (IHC) was performed to determine the expression of the four genes.ResultsWe found that the proportion of epithelial cells was obviously large in COAD samples. Further analysis of epithelial cells showed that the activity of the enterocytes was highest in the cell-cell communication network. Based on enterocyte data, 30 ERDEGs were identified and a 4-gene prognostic model including CPM, CLCA4, ELOVL6, and ATP2A3 was developed and validated. The risk score derived from this model was considered as an independent variable factor to predict overall survival. The patients were divided into high- and low-risk groups based on the median riskscore value. The correlation between immune cell infiltration, immunotherapy response, immune status, clinical characteristics, drug sensitivity, and risk score was analyzed. IHC confirmed the expression of signature genes in tissues from normal individuals, patients with polyps, and COAD.ConclusionIn this study, we constructed and validated a novel four-gene signature prognostic model, which could effectively predict the response to immunotherapy and overall survival in patients with COAD. More importantly, this model provides useful insight into the management of colon cancer patients and aids in designing personalized therapy.

show abstract

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma

Cited by 7 publications

References 52 publications

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells

Metabolomics, Transcriptomics and Functional Glycomics Reveals Bladder Cancer Cells Plasticity and Enhanced Aggressiveness Facing Hypoxia and Glucose Deprivation

A novel enterocyte-related 4-gene signature for predicting prognosis in colon adenocarcinoma

Contact Info

Product

Resources

About