High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer

Inasu, Maria; Bendahl, Pär‐Ola; Fernö, Mårten; Malmström, Per; Borgquist, Signe; Kimbung, Siker

doi:10.1038/s41523-021-00333-6

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…3A). As previously reported (40), the analysis of transcriptomic database (TNMplot) showed that CYP27A1 is expressed in breast cancer in paired tumors (n=7569), adjacent normal breast tissues (n=252) and metastasis (n=82), showing a slight decrease between normal and cancer tissues (Fig 3B). The cell lines used in our studies were chosen because they were reported to express CYP27A1 at various mRNA levels (https://www.proteinatlas.org/), and we confirm that at the protein level by western blotting (Fig 3C).…”

Section: Resultssupporting

confidence: 83%

27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumor

Ayadi,

Friedrichs,

Soulès

et al. 2023

Preprint

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Oncosterone (6-oxo-cholestane-3beta,5alpha-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha positive breast cancer (ER(+) BC) and triple negative breast cancers (TN BC). OCDO is an oxysterol formed in three steps from cholesterol: 1) oxygen addition at the double bond to give alpha- or beta- isomers of 5,6-epoxycholestanols (5,6-EC), 2) hydrolyses of the epoxide ring of 5,6-ECs to give cholestane-3beta, 5alpha, 6beta-triol (CT), and 3) oxidation of the C6 hydroxyl of CT to give OCDO. On the other hand, cholesterol can be hydroxylated by CYP27A1 at the ultimate methyl carbon of its side chain to give 27-hydroxycholesterol (27HC), which is a tumor promoter for ER(+) BC. It is currently unknown whether OCDO and its precursors can be hydroxylated at position C27 by CYP27A1, as is the impact of such modification on the proliferation of ER(+) and TN BC cells. We investigated, herein, whether 27-hydroxylated-5,6-ECs, -CT and -OCDO exist as metabolites and can be produced by cells expressing CYP27A1. We report, for the first time, that these compounds exist as metabolites in human. We give pharmacological and genetic evidences that CYP27A1 is responsible for their production. Importantly, we found that 27-hydroxy-OCDO (27H-OCDO) inhibits BC cells proliferation and blocks OCDO and 27-HC induced proliferation in BC cells, showing that this metabolic conversion commutes the proliferative properties of OCDO into antiproliferative ones. These data suggest an unprecedented role of CYP27A1 in the control of breast carcinogenesis by inhibiting the tumor promoter activities of oncosterone and 27-HC.

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Section: Resultssupporting

confidence: 83%

27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumor

Ayadi,

Friedrichs,

Soulès

et al. 2023

Preprint

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“…We systematically assessed the expression level and clinical significance of CYP27A1 in LUAD. Based on our findings, a poor prognosis for LUAD patients was found to be associated with low expression of CYP27A1, which is consistent with the effect of CYP27A1 on prognosis in breast cancer [ 28 ].…”

Section: Discussionsupporting

confidence: 81%

Transcriptomic analysis identifies CYP27A1 as a diagnostic marker for the prognosis and immunity in lung adenocarcinoma

Yin,

He,

Huang

et al. 2023

BMC Immunol

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Background The association between lipid metabolism disorder and carcinogenesis is well-established, but there is limited research on the connection between lipid metabolism-related genes (LRGs) and lung adenocarcinoma (LUAD). The objective of our research was to identify LRGs as the potential biomarkers for prognosis and assess their impact on immune cell infiltration in LUAD. Methods We identified novel prognostic LRGs for LUAD patients via the bioinformatics analysis. CYP27A1 expression level was systematically evaluated via various databases, such as TCGA, UALCAN, and TIMER. Subsequently, LinkedOmics was utilized to perform the CYP27A1 co-expression network and GSEA. ssGSEA was conducted to assess the association between infiltration of immune cells and CYP27A1 expression. CYP27A1’s expression level was validated by qRT-PCR analysis. Results CYP27A1 expression was decreased in LUAD. Reduced CYP27A1 expression was linked to unfavorable prognosis in LUAD. Univariate and multivariate analyses indicated that CYP27A1 was an independent prognostic biomarker for LUAD patients. GSEA results revealed a positive correlation between CYP27A1 expression and immune-related pathways. Furthermore, CYP27A1 expression was positively correlated with the infiltration levels of most immune cells. Conclusion CYP27A1 is a potential biomarker for LUAD patients, and our findings provided a novel perspective to develop the prognostic marker for LUAD patients.

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“…Inhibiting cholesterol conversion to 27-hydroxycholesterol via CYP27A1 has been suggested to prevent breast cancer tumor progression [ 29 ]. However, a study of estrogen receptor positive primary breast cancer showed that high CYP27A1 expression is associated with favorable prognosis [ 30 ]. Studies demonstrated that CYP27A1 deficiency increased the proliferative activity of melanoma cells [ 31 ] and prostate cancer cells [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1

et al. 2023

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Cholesterol metabolism plays a critical role in the progression of hepatocellular carcinoma (HCC), but it is not clear how cholesterol metabolism is regulated. The tubulin beta class I genes (TUBBs) are associated with the prognosis of many different cancers. To confirm the function of TUBBs in HCC, the Kaplan–Meier method and Cox analyses were performed using TCGA and GSE14520 datasets. A higher expression of TUBB2B is an independent prognostic factor for shorter over survival in HCC patients. Deletion of TUBB2B in hepatocytes inhibits proliferation and promotes tumor cell apoptosis, while over-expression of TUBB2B has the opposite function. This result was confirmed in a mouse xenograft tumor model. Mechanistically, TUBB2B induces the expression of CYP27A1, an enzyme responsible for the conversion of cholesterol to 27-hydroxycholesterol, which leads to the up-regulation of cholesterol and the progression of HCC. In addition, TUBB2B regulates CYP27A1 via human hepatocyte nuclear factor 4alpha (HNF4A). These findings indicated that TUBB2B functions as an oncogene in HCC, and plays a role in promoting cell proliferation and anti-apoptosis through targeting HNF4A/CYP27A1/cholesterol.

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High CYP27A1 expression is a biomarker of favorable prognosis in premenopausal patients with estrogen receptor positive primary breast cancer

Cited by 10 publications

References 36 publications

27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumor

27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumor

Transcriptomic analysis identifies CYP27A1 as a diagnostic marker for the prognosis and immunity in lung adenocarcinoma

TUBB2B facilitates progression of hepatocellular carcinoma by regulating cholesterol metabolism through targeting HNF4A/CYP27A1

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