In Silico Analysis for Sphingolipid Metabolism-Related Genes in Human Kidney Clear Cell Carcinoma Using The Cancer Genome Atlas.

Park, Woo‐Jae; Park, Jee Young; Kwon, Taeg Kyu; Park, Jong‐Wook; Kim, Shin

doi:10.46308/kmj.2020.00101

Cited by 2 publications

(3 citation statements)

References 33 publications

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“…Our finding of reduced SphK1 mRNA level in the ccRCC of higher malignancy grades compared to the G2 tumors may seem puzzling considering the cancer‐promoting role of this enzyme. In all available studies, SphK1 expression in the ccRCC was found to be higher than in the adjacent healthy tissue 22–25 . However, in contrast to our report, these studies did not investigate quantitative changes in the expression of the enzyme across different malignancy grades.…”

Section: Discussioncontrasting

confidence: 86%

“…In all available studies, SphK1 expression in the ccRCC was found to be higher than in the adjacent healthy tissue. [22][23][24][25] However, in contrast to our report, these studies did not investigate quantitative changes in the expression of the enzyme across different malignancy grades. It should be noted that when we performed statistical analysis on the combined data from all ccRCC grades, the difference in SphK1 mRNA and protein level between the tumor and the healthy tissue was highly significant (p < 0.002 and p < 0.004, respectively).…”

Section: F I G U R Econtrasting

confidence: 75%

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Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

Młynarczyk

Mikłosz

Suchański

et al. 2022

J of Cellular Biochemistry

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There is a host of evidence for the role of bioactive sphingolipids in cancer biology, and dysregulated sphingolipid metabolism was observed in many malignant tumors. The aim of the present study was to provide more detailed data on sphingolipid metabolism in different stages of clear cell renal cell carcinoma (ccRCC). Samples of the tumor and noncancerous fragments of the same kidney were collected from patients who underwent a radical nephrectomy. The subjects were stratified according to the degree of malignancy of the tumor (n = 14 for G2, 12 for G3, and 9 for G4). The content of bioactive sphingolipids/glycosphingolipids was measured with an HPLC and HPTLC method, and the mRNA and protein expression of sphingolipid transporters and metabolizing enzymes was evaluated using real‐time polymerase chain reaction (PCR) and Western blot, respectively. Compared to healthy kidney tissue, ccRCC was characterized by accumulation of sphingosine, sphingosine‐1‐phosphate (S1P), ceramide, dihydrosphingosine, and dihydroceramide. However, in the case of the latter two, the accumulation was limited to higher malignancy grades. In addition, compared to the healthy tissue, the content of gangliosides in the tumor was increased at the expense of globosides. We also found profound grade‐dependent changes in the mRNA level of S1P‐metabolizing enzymes, and spinster homolog 2. In general, their expression was much higher in G2 tumors compared to higher malignancy grades. We conclude that ccRCC is characterized by profound and multilevel alterations in sphingolipid metabolism, which to a large extent are grade‐dependent. We hypothesize that dysregulation of sphingolipid metabolism contributes to the progression of ccRCC.

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Section: Discussioncontrasting

confidence: 86%

Section: F I G U R Econtrasting

confidence: 75%

Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

Młynarczyk

Mikłosz

Suchański

et al. 2022

J of Cellular Biochemistry

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“…One of the only pathways enriched progressors in the GSEA results was ‘’SPHINGOLIPID METABOLISM’’. In a recent paper, several genes from that pathway were linked to ccRCC progression [ 43 ]. In our data, 5 of those 6 genes fit with the authors’ findings, i.e., the gene direction of the deregulation indicated a worse prognosis in the progressive patients.…”

Section: Discussionmentioning

confidence: 99%

AGAP2-AS1 as a prognostic biomarker in low-risk clear cell renal cell carcinoma patients with progressing disease

et al. 2021

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Background Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer and one of the most common cancers. While survival for localized ccRCC is good, the survival of metastatic disease is not, and thirty percent of patients with ccRCC develop metastases during follow-up. Although current scoring methods accurately identify patients at low progression risk, a small subgroup of those patients still experience metastasis. We therefore aimed to identify ccRCC progression biomarkers in “low-risk” patients who were potentially eligible for adjuvant treatments or more intensive follow-up. Methods We assembled a cohort of ccRCC patients (n = 443) and identified all “low-risk” patients who later developed progressing tumors (n = 8). Subsequently, we performed genome-wide expression profiling from formalin-fixed samples obtained at initial surgery from these “low-risk” patients and 16 matched patients not progressing to recurrence with metastasis. The patients were matched for Leibovich sore, creatinine, age, sex, tumor size and tumor stage. Key results were confirmed with qPCR and external data from The Cancer Genome Atlas. Results Principal component analysis indicated that systematic transcriptomic differences were already detectable at the time of initial surgery. One thousand one hundred sixty-seven genes, mainly associated with cancer and immune-related pathways, were differentially expressed between progressors and nonprogressors. A search for a classifier revealed that overexpression of AGAP2-AS1, an antisense long noncoding RNA, correctly classified 23 of 24 samples, years (4.5 years average) in advance of the discovery of metastasis and without requiring larger gene panels. Subsequently, we confirmed AGAP2-AS1 gene overexpression by qPCR in the same samples (p < 0.05). Additionally, in external data from The Cancer Genome Atlas, overexpression of AGAP2-AS1 is correlated with overall unfavorable survival outcome in ccRCC, irrespective of other prognostic predictors (p = 2.44E−7). Conclusion AGAP2-AS1 may represent a novel biomarker identifying high-risk ccRCC patients currently classified as “low risk” at the time of surgery.

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In Silico Analysis for Sphingolipid Metabolism-Related Genes in Human Kidney Clear Cell Carcinoma Using The Cancer Genome Atlas.

Cited by 2 publications

References 33 publications

Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

Grade‐dependent changes in sphingolipid metabolism in clear cell renal cell carcinoma

AGAP2-AS1 as a prognostic biomarker in low-risk clear cell renal cell carcinoma patients with progressing disease

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