Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study

Gonzalo-Calvo, David de; López‐Vilaró, Laura; Nasarre, Laura; Pérez-Olabarría, Maitane; Vázquez, Tania; Escuín, Daniel; Badimon, Lina; Barnadas, Agustí; Lerma, Enrique; Llorente‐Cortés, Vicenta

doi:10.1186/s12885-015-1469-5

Cited by 182 publications

(166 citation statements)

References 47 publications

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“…The metabolic effect of CE in breast cancer remains poorly understood. But the relationship between CE and poor clinical outcome in human breast cancer has been reported [40]. These studies have indicated that these selected lipid species could be classified as biomarkers for the diagnosis of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions

et al. 2016

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BackgroundBreast cancer is very common and highly fatal in women. Current non-invasive detection methods like mammograms are unsatisfactory. Lipidomics, a promising detection method, may serve as a novel prognostic approach for breast cancer in high-risk patients.ResultsAccording the predictive model, the combination of 15 lipid species had high diagnostic value. In the training set, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the combination of these 15 lipid species were 83.3%, 92.7%, 89.7%, and 87.9%, respectively. The AUC in the training set was 0.926 (95% CI 0.869-0.982). Similar results were found in the validation set, with the sensitivity, specificity, PPV and NPV at 81.0%, 94.5%, 91.9%, and 86.7%, respectively. The AUC was 0.938 (95% CI 0.889-0.986) in the validation set.MethodsUsing triple quadrupole liquid chromatography electrospray ionization tandem mass spectrometry, this study was to detect global lipid profiling of a total of 194 plasma samples from 84 patients with early-stage breast cancer (stage 0–II) and 110 patients with benign breast disease included in a training set and a validation set. A binary logistic regression was used to build a predictive model for evaluating the lipid species as potential biomarkers in the diagnosis of breast cancer.ConclusionThe combination of these 15 lipid species as a panel could be used as plasma biomarkers for the diagnosis of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions

et al. 2016

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“…1, 2 Evidence suggests a major role for lipids in the progression of hematological 3–5 and other malignancies 6–10 with specific involvement of cholesterol and cholesteryl esters, along with the high-density lipoproteins (HDL) that carry them. 11–14 In the case of B-cell lymphoma, B-cell receptor (BCR) signaling, including low level, tonic signaling observed in germinal center (GC)-derived diffuse large B cell lymphoma (DLBCL) and chronic active signaling in activated B-cell (ABC) DLBCL, has been shown to directly promote cholesterol biosynthesis through intermediate kinases downstream of the BCR to maintain cell membrane integrity and BCR signaling.…”

Section: Introductionmentioning

confidence: 99%

Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin

et al. 2017

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Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1). As we previously reported, GC DLBCL are exquisitely sensitive to HDL NP as monotherapy while ABC DLBCL are less sensitive. Herein, we report that enhanced BCR signaling and resultant de novo cholesterol synthesis in ABC DLBCL drastically reduces the ability of HDL NPs to reduce cellular cholesterol and induce cell death. Therefore, we combined HDL NP with the BCR signaling inhibitor ibrutinib and the SYK inhibitor R406. By targeting both cellular cholesterol uptake and BCR-associated de novo cholesterol synthesis, we achieved cellular cholesterol reduction and induced apoptosis in otherwise resistant ABC DLBCL cell lines. These results in lymphoma demonstrate that reduction of cellular cholesterol is a powerful mechanism to induce apoptosis. Cells rich in cholesterol require HDL NP therapy to reduce uptake and molecularly targeted agents that inhibit upstream pathways that stimulate de novo cholesterol synthesis, thus, providing a new paradigm for rationally targeting cholesterol metabolism as therapy for cancer.

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“…As the most important mediator in HDL-cholesterol metabolism, SR-B1 has been reported in several cancers. 10,11,13,15 Nevertheless, we knew little about the roles of SR-B1 in ccRCC. In our study, we explored the expression of SR-B1 in ccRCC tissues and found that SR-B1 expression was much higher in cancerous tissues compared with their normal counterparts.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma

Lou

et al. 2017

Tumour Biol.

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Aberrant expression of scavenger receptor class B type 1 has been reported in several human cancers. Nevertheless, the roles of scavenger receptor class B type 1 in clear cell renal cell carcinoma remain unclear. The aim of this study was to evaluate the diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma. The messenger RNA level of scavenger receptor class B type 1 in clear cell renal cell carcinoma tissues was detected by quantitative reverse transcription polymerase chain reaction, while protein level was determined by western blot and immunohistochemistry. The lipid content between clear cell renal cell carcinoma tissues and normal kidney tissues was differentiated by Oil Red O and hematoxylin-eosin staining. The diagnostic value of scavenger receptor class B type 1 was determined by receiver operating characteristic curve. The prognostic significance of scavenger receptor class B type 1 was assessed by Kaplan-Meier analysis and Cox regression analysis. Our results showed that the expression of scavenger receptor class B type 1 in clear cell renal cell carcinoma tissues at both messenger RNA and protein level was much higher than that in normal kidney tissues. Receiver operating characteristic curve analysis exhibited a significant value of area under the curve (0.8486, 95% confidence interval: 0.7926-0.9045) with strong sensitivity (0.75, 95% confidence interval: 0.6535-0.8312) and specificity (0.90, 95% confidence interval: 0.8238-0.9510). Kaplan-Meier analysis revealed that patients with higher scavenger receptor class B type 1 expression had shorter progression-free survival time. Cox analysis indicated that scavenger receptor class B type 1 was an independent prognostic biomarker. In conclusion, our findings implied that scavenger receptor class B type 1 might serve as a diagnostic and independent prognostic biomarker in clear cell renal cell carcinoma.

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Intratumor cholesteryl ester accumulation is associated with human breast cancer proliferation and aggressive potential: a molecular and clinicopathological study

Cited by 182 publications

References 47 publications

Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions

Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions

Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin

Diagnostic and prognostic value of scavenger receptor class B type 1 in clear cell renal cell carcinoma

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