The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery

Meo, Nicola Antonio di; Lasorsa, Francesco; Rutigliano, Monica; Milella, Martina; Ferro, Matteo; Battaglia, Michele; Ditonno, Pasquale; Lucarelli, Giuseppe

doi:10.1080/14737159.2023.2195553

Cited by 52 publications

(26 citation statements)

References 195 publications

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“…[1] The most typical histological subtype of RCC and the leading cause of death from RCC is clear cell renal cell carcinoma (ccRCC). [2,3] RCC was perhaps the exemplar of malignancies characterized by metabolic reprogramming, [4][5][6][7][8] which refers to glucose metabolism, [9][10][11] the tricarboxylic acid cycle, [12,13] lipid metabolism [14,15] and amino acid metabolism. [16,17] Therefore kidney cancer is referred to as a metabolic disease.…”

Section: Introductionmentioning

confidence: 99%

Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment

Tang,

Zheng,

et al. 2024

Medicine

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Background: Previous studies have revealed the critical functions of NEK2 in controlling the cell cycle which is linked to poor prognosis in multiple tumor types, but less research has been devoted to clear cell renal cell carcinoma (ccRCC). Methods: We downloaded clinical data from the gene expression omnibus (GEO) and TCGA databases together with transcriptional and mutational datasets. Strongly coexpressed genes with NEK2 were extracted from TCGA-KIRC cohort, and were submitted to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for functional analyses. According to NEK2 levels, the survival status, mutational characteristics, response to immunotherapy and sensitivity to drugs of the patients were studied. The potential correlations between NEK2 levels and immune cell state as well as immune cell infiltration were examined using the GEPIA, TIMER and TISIDB databases. Double immunofluorescence (IF) was performed to identify the NEK2 overexpression and relationship with CD8 in ccRCC. Results: The NEK2 gene was overexpressed and would enhance the nuclear division and cell cycle activities in ccRCC. ccRCC patients with high NEK2 expression had worse clinical outcomes, higher mutation burden and better therapeutic response. Moreover, NEK2 gene overexpression was positively related to various immune cell marker sets, which was also proved by validation cohort, and more infiltration of various immune cells. Conclusion: ccRCC patients with NEK2 high expression have a poorer prognosis than those with NEK2 low expression, resulting from its function of promoting proliferation, accompanied by increased infiltration of CD8 + T cells and Tregs and T-cell exhaustion and will respond better to proper treatments.

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Section: Introductionmentioning

confidence: 99%

Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment

Tang,

Zheng,

et al. 2024

Medicine

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“…Therefore, to maximize the therapeutic effects of treatment, patients must be stratified based on heterogeneity. Clear cell renal cell carcinoma (ccRCC) cells are distinguished by their characteristic morphology, featuring cytoplasm with accumulations of lipids and glycogen, forming clear vacuoles [ 5 , 6 ]. At its core, ccRCC represents a metabolic disorder characterized by the reprogramming of energy metabolism, driven by mutations in key genes involved in metabolic pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Acting as regulators, lncRNAs exhibit extensive and nuanced effects on the metabolic pathways and products of ccRCC, exerting influence either directly or indirectly. This integrated regulatory role underscores their significance in advancing research on tumor metabolism, facilitating the discovery of novel tumor biomarkers, and pinpointing potential therapeutic targets for future investigations [ 5 , 7 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies

Wang,

Liu,

Tang

et al. 2024

Eur J Med Res

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Background PCD-related long non-coding RNAs (PRLs) are rarely investigated in relation to clear cell renal carcinoma (ccRCC). As part of this study, we evaluated the immunological potential of PRL signatures as a biomarker for ccRCC prognosis and immunological function. Materials and methods Data were downloaded from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. A Pearson correlation analysis was conducted on the 27 PCD-associated genes to determine whether lncRNAs were significantly associated with PCD. Kaplan–Meier analysis, biological function identification, immune infiltration analysis, estimation of efficacy of immunotherapy and targeted drug screening, and exploration of the landscape of mutation status were conducted by analyzing the risk scores. Results Seven PRLs, LINC02747, AP001636.3, AC022126.1, LINC02657, LINC02609, LINC02154, and ZNNT1, were used to divide patients with ccRCC into groups with high and low risk. High-risk patients had a worse prognosis than low-risk patients, according to the results, and the PRL signature showed promising predictive ability. More immune cells were clustered in the high-risk group, whereas the immune cell function of the low-risk group was significantly suppressed. The high-risk group was less sensitive to immunotherapy, whereas the low-risk group had positive responses to most drugs. Conclusions Collectively, we established and verified a PRL signature that could competently guide the prognostic survival and immunotherapy of ccRCC. In addition, molecular subtypes were determined for ccRCC based on PRL expression, which may help elucidate the underlying molecular mechanism of ccRCC and develop targeted treatments.

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“…In RCC, HIF is constitutively activated, leading to increased expression of genes involved in glycolysis, angiogenesis, and survival pathways. The metabolic alterations observed in RCC, in association with intratumor heterogeneity, have an important role in the chemo-resistant mechanisms described in this tumor [ 11 , 12 , 13 , 14 ]. Furthermore, considering that up to 30% of these patients present metastatic disease at diagnosis, and around 20–30% of patients undergoing surgery will suffer recurrence, we need to identify novel therapeutic targets [ 15 , 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice

et al. 2023

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Renal cell carcinoma (RCC) is the seventh most common cancer in men and the ninth most common cancer in women worldwide. There is plenty of evidence about the role of the immune system in surveillance against tumors. Thanks to a better understanding of immunosurveillance mechanisms, immunotherapy has been introduced as a promising cancer treatment in recent years. Renal cell carcinoma (RCC) has long been thought chemoresistant but highly immunogenic. Considering that up to 30% of the patients present metastatic disease at diagnosis, and around 20–30% of patients undergoing surgery will suffer recurrence, we need to identify novel therapeutic targets. The introduction of immune checkpoint inhibitors (ICIs) in the clinical management of RCC has revolutionized the therapeutic approach against this tumor. Several clinical trials have shown that therapy with ICIs in combination or ICIs and the tyrosine kinase inhibitor has a very good response rate. In this review article we summarize the mechanisms of immunity modulation and immune checkpoints in RCC and discuss the potential therapeutic strategies in renal cancer treatment.

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The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery

Cited by 52 publications

References 195 publications

Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment

Function of NEK2 in clear cell renal cell carcinoma and its effect on the tumor microenvironment

Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies

Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice

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