An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

Liu, Rong‐Zong; Godbout, Roseline

doi:10.3390/cancers12123823

Cited by 23 publications

(24 citation statements)

References 133 publications

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“…Reprogramming of tumor metabolism played a signi cant role in tumor metastasis [21,22]. Plenty of tumor metabolism related genes had been discovered [23][24][25][26]. Among the H-DEGs, iron metabolism related genes including GOT1 and CP [27,28], glutamine metabolism related gene GOT1 [29], pyruvate metabolism related gene PC [30], proline metabolism related gene ALDH4A1 [31], and so on were found in this study.…”

Section: Discussionmentioning

confidence: 58%

Identification of MARCO and PCSK6 As Key Genes Promoting Hepatic Metastasis in Pancreatic Cancer via Bioinformatics Analysis

Liang

2022

Preprint

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Background: Hepatic metastasis occurred frequently in pancreatic cancer and leads to a poor prognosis. Genes promoting hepatic metastasis would help finding out the way to improve survivals of patients. Methods and results: GSE42952 and GSE71729 out of 181 data serials from Gene Expression Omnibus (GEO) with samples of both hepatic metastasis and primary tumor of pancreatic cancer were chosen to generate differentially expressing genes (DEGs). 217 up-regulated and 257 down-regulated genes overlapped between the two data serials and were defined as hepatic metastasis related DEGs (H-DEGs), among which 27 up-regulated and 2 down-regulated H-DEGs were verified by both tumor tissues and cell lines of pancreatic cancer. Gene ontology (GO) and KEGG pathway analysis were performed and showed reprogramming of tumor metabolism might promote hepatic metastasis. The prognostic significance of H-DEGs were investigated. Up-regulation of MARCO and PCSK6 were both correlated to decreased overall survivals in pancreatic cancer. Immune cell infiltration analysis indicated MARCO involved in regulating tumor immune microenvironment. Gene set enrichment analysis found PCSK6 was related to activations of critical pathways and regulation of glycolysis. Conclusions: MARCO and PCSK6 might promote hepatic metastasis of pancreatic cancer via modulating tumor immune microenvironment and tumor metabolism respectively.

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Section: Discussionmentioning

confidence: 58%

Identification of MARCO and PCSK6 As Key Genes Promoting Hepatic Metastasis in Pancreatic Cancer via Bioinformatics Analysis

Liang

2022

Preprint

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“…FABP4, FABP5, FABP8, FABP9, and FABP12 loci were found in a commonly amplified region within the chromosome 8 (8q21.13), frequently observed in human PCas mets. In line with this, increased mRNA levels of FABP 4, 8, 9, and 12 were associated with increased Gleason score and PCa recurrence (90). In 2020, Liu and coworkers also demonstrated that FABP12 promotes EMT and PCa cell motility, at least in part, through a PPARg-dependent pathway (113), while FABP9 suppression inhibits PC3 cell invasive potential in PPARgindependent manner (86).…”

Section: Alterations In Fa Transportmentioning

confidence: 75%

“…FABP5 is the most characterized and highly expressed FABP in human PCas and cell lines, especially in CRPC cells (81)(82)(83)(84)(85)(86)(87)(88). Different mechanisms account for FABP5 upregulation, including a positive feedback loop mediated by include proliferator-activated receptors (PPAR) PPARb/d (89), CpG island hypomethylation (85), and gene amplification (90). The latter is highly frequent in advanced CRPC (88).…”

Section: Alterations In Fa Transportmentioning

confidence: 99%

Prostate Cancer Progression: as a Matter of Fats

2021

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Advanced prostate cancer (PCa) represents the fifth cause of cancer death worldwide. Although survival has improved with second-generation androgen signaling and Parp inhibitors, the benefits are not long-lasting, and new therapeutic approaches are sorely needed. Lipids and their metabolism have recently reached the spotlight with accumulating evidence for their role as promoters of PCa development, progression, and metastasis. As a result, interest in targeting enzymes/transporters involved in lipid metabolism is rapidly growing. Moreover, the use of lipogenic signatures to predict prognosis and resistance to therapy has been recently explored with promising results. Despite the well-known association between obesity with PCa lethality, the underlying mechanistic role of diet/obesity-derived metabolites has only lately been unveiled. Furthermore, the role of lipids as energy source, building blocks, and signaling molecules in cancer cells has now been revisited and expanded in the context of the tumor microenvironment (TME), which is heavily influenced by the external environment and nutrient availability. Here, we describe how lipids, their enzymes, transporters, and modulators can promote PCa development and progression, and we emphasize the role of lipids in shaping TME. In a therapeutic perspective, we describe the ongoing efforts in targeting lipogenic hubs. Finally, we highlight studies supporting dietary modulation in the adjuvant setting with the purpose of achieving greater efficacy of the standard of care and of synthetic lethality. PCa progression is “a matter of fats”, and the more we understand about the role of lipids as key players in this process, the better we can develop approaches to counteract their tumor promoter activity while preserving their beneficial properties.

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“…Consequently, novel prognostic biomarkers and treatments for BLCA need to be identified to improve patient prognosis. Accumulating studies have suggested that lipid metabolism dysregulation was involved in development and progression of various cancers, including lung cancer [ 18 ], prostate cancer [ 19 ], gastric carcinoma [ 20 ], and BLCA [ 13 ]. Despite the crucial role of lipid metabolism in BLCA, studies about the relationship between lipid metabolism and BLCA prognosis are rare.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a novel lipid metabolism-related gene prognostic signature and candidate drugs for patients with bladder cancer

et al. 2021

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Background Bladder cancer (BLCA) is a common cancer associated with an unfavorable prognosis. Increasing numbers of studies have demonstrated that lipid metabolism affects the progression and treatment of tumors. Therefore, this study aimed to explore the function and prognostic value of lipid metabolism-related genes in patients with bladder cancer. Methods Lipid metabolism-related genes (LRGs) were acquired from the Molecular Signature Database (MSigDB). LRG mRNA expression and patient clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a signature for predicting overall survival of patients with BLCA. Kaplan-Meier analysis was performed to assess prognosis. The connectivity Map (CMAP) database was used to identify small molecule drugs for treatment. A nomogram was constructed and assessed by combining the signature and other clinical factors. The CIBERSORT, MCPcounter, QUANTISEQ, XCELL, CIBERSORT-ABS, TIMER and EPIC algorithms were used to analyze the immunological characteristics. Results An 11-LRG signature was successfully constructed and validated to predict the prognosis of BLCA patients. Furthermore, we also found that the 11-gene signature was an independent hazardous factor. Functional analysis suggested that the LRGs were closely related to the PPAR signaling pathway, fatty acid metabolism and AMPK signaling pathway. The prognostic model was closely related to immune cell infiltration. Moreover, the expression of key immune checkpoint genes (PD1, CTLA4, PD-L1, LAG3, and HAVCR2) was higher in patients in the high-risk group than in those in the low-risk group. The prognostic signature based on 11-LRGs exhibited better performance in predicting overall survival than conventional clinical characteristics. Five small molecule drugs could be candidate drug treatments for BLCA patients based on the CMAP dataset. Conclusions In conclusion, the current study identified a reliable signature based on 11-LRGs for predicting the prognosis and response to immunotherapy in patients with BLCA. Five small molecule drugs were identified for the treatments of BLCA patients.

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An Amplified Fatty Acid-Binding Protein Gene Cluster in Prostate Cancer: Emerging Roles in Lipid Metabolism and Metastasis

Cited by 23 publications

References 133 publications

Identification of MARCO and PCSK6 As Key Genes Promoting Hepatic Metastasis in Pancreatic Cancer via Bioinformatics Analysis

Identification of MARCO and PCSK6 As Key Genes Promoting Hepatic Metastasis in Pancreatic Cancer via Bioinformatics Analysis

Prostate Cancer Progression: as a Matter of Fats

Development and validation of a novel lipid metabolism-related gene prognostic signature and candidate drugs for patients with bladder cancer

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