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Sawada MIBAC, de Fátima Mello Santana M, Reis M, de Assis SIS, Pereira LA, Santos DR, Nunes VS, Correa-Giannella MLC, Gebrim LH, Passarelli M. Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors. Sci Rep 2023; 13:8998. [PMID: 37268673 DOI: 10.1038/s41598-023-35764-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 05/23/2023] [Indexed: 06/04/2023] Open
Abstract
The association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naïve BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and 14C-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes.
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Affiliation(s)
- Maria Isabela Bloise Alves Caldas Sawada
- Programa de Pós-Graduação em Medicina, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil
- Centro de Referência da Saúde da Mulher (Hospital Pérola Byington), São Paulo, Brazil
- Hospital da Força Aérea de São Paulo, São Paulo, Brazil
| | - Monique de Fátima Mello Santana
- Laboratório de Lípides (LIM10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Mozania Reis
- Programa de Pós-Graduação em Medicina, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil
- Unidade Básica de Saúde Dra. Ilza Weltman Hutzler, São Paulo, Brazil
| | - Sayonara Ivana Santos de Assis
- Laboratório de Lípides (LIM10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Lucas Alves Pereira
- Programa de Pós-Graduação em Medicina, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil
| | - Danielle Ribeiro Santos
- Laboratório de Lípides (LIM10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Valéria Sutti Nunes
- Laboratório de Lípides (LIM10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Maria Lucia Cardillo Correa-Giannella
- Laboratório de Carboidratos e Radioimunoensaio Lípides (LIM18), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Luiz Henrique Gebrim
- Centro de Referência da Saúde da Mulher (Hospital Pérola Byington), São Paulo, Brazil
| | - Marisa Passarelli
- Programa de Pós-Graduação em Medicina, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil.
- Laboratório de Lípides (LIM10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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Feng J, Symonds EA, Karnes JH. Visualization and Quantification of the Association Between Breast Cancer and Cholesterol in the All of Us Research Program. Cancer Inform 2023; 22:11769351221144132. [PMID: 36654923 PMCID: PMC9841847 DOI: 10.1177/11769351221144132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/21/2022] [Indexed: 01/15/2023] Open
Abstract
Epidemiologic evidence for the association of cholesterol and breast cancer is inconsistent. Several factors may contribute to this inconsistency, including limited sample sizes, confounding effects of antihyperlipidemic treatment, age, and body mass index, and the assumption that the association follows a simple linear function. Here, we aimed to address these factors by combining visualization and quantification a large-scale contemporary electronic health record database (the All of Us Research Program). We find clear visual and quantitative evidence that breast cancer is strongly, positively, and near-linearly associated with total cholesterol and low-density lipoprotein cholesterol, but not associated with triglycerides. The association of breast cancer with high-density lipoprotein cholesterol was non-linear and age dependent. Standardized odds ratios were 2.12 (95% confidence interval 1.9-2.48), P = 5.6 × 10-31 for total cholesterol; 1.99 (1.75-2.26), P = 2.6 × 10-26 for low-density lipoprotein cholesterol; 1.69 (1.3-2.2), P = 9.0 × 10-5 for high-density lipoprotein cholesterol at age < 56; and 0.65 (0.55-0.78), P = 1.2 × 10-6 for high-density lipoprotein cholesterol at age ⩾ 56. The inclusion of the lipid levels measured after antihyperlipidemic treatment in the analysis results in erroneous associations. We demonstrate that the use of the logistic regression without inspecting risk variable linearity and accounting for confounding effects may lead to inconsistent results.
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Affiliation(s)
- Jianglin Feng
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA
| | | | - Jason H Karnes
- Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA
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Subramaniam S, Kong YC, Yip CH, Thiagarajan M, Pailoor J, Zaharah H, Taib NA, See MH, Sarfati D, Bhoo-Pathy N. Association between pre-existing cardiometabolic comorbidities and the pathological profiles of breast cancer at initial diagnosis: a cross sectional study. Ecancermedicalscience 2023; 17:1512. [PMID: 37113731 PMCID: PMC10129381 DOI: 10.3332/ecancer.2022.1512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Indexed: 04/29/2023] Open
Abstract
The presence of comorbidities has been associated with later stages of breast cancer diagnosis. It is unclear whether biological mechanisms are partly responsible. We examined the association between the presence of pre-existing comorbidities and tumour profile at initial diagnosis with breast cancer. Data for the present analysis were derived from a prior inception cohort study comprising 2,501 multiethnic women, newly diagnosed with breast cancer between 2015 and 2017 in four hospitals across Klang Valley. At the inception of the cohort, medical and drug histories, height, weight and blood pressure were recorded. Blood samples were taken to measure serum lipid and glucose. Modified Charlson Comorbidity Index (CCI) was calculated using data extracted from medical records. The association of CCI as well as specific comorbidities, with pathological breast cancer profile was analysed. Higher comorbidity burden, namely cardiometabolic conditions were associated with unfavourable pathological features including larger tumours, involvement of >9 axillary lymph nodes, distant metastasis and human epidermal growth factor receptor 2 overexpression. These associations remained largely significant following multivariable analyses. Specifically, diabetes mellitus was independently associated with high nodal metastasis burden. Low level of high-density lipoprotein was associated with larger tumours (>5 cm), and distant metastasis. Evidence from this study seems to support the hypothesis that the later stages of breast cancer diagnosis in women with (cardiometabolic) comorbidities may be partially explained by underlying pathophysiological events.
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Affiliation(s)
- Shridevi Subramaniam
- Centre for Clinical Epidemiology, Institute for Clinical Research, National Institutes of Health, Ministry of Health, Shah Alam 40170, Malaysia
| | - Yek-Ching Kong
- Centre for Epidemiology and Evidence-Based Medicine, Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Cheng-Har Yip
- Subang Jaya Medical Centre, Subang Jaya 47500, Malaysia
| | - Muthukkumaran Thiagarajan
- Department of Radiotherapy and Oncology, Kuala Lumpur Hospital, Ministry of Health, Kuala Lumpur 50586, Malaysia
| | | | - Hafizah Zaharah
- Department of Radiotherapy and Oncology, National Cancer Institute, Ministry of Health, Putrajaya 62250, Malaysia
| | - Nur Aishah Taib
- Department of Surgery, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Mee-Hoong See
- Department of Surgery, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
| | - Diana Sarfati
- National Director of Cancer Control, and Chief Executive Cancer Control Agency, PO Box 5013, Wellington 6140, New Zealand
| | - Nirmala Bhoo-Pathy
- Centre for Epidemiology and Evidence-Based Medicine, Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
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Abdalkareem Jasim S, Kzar HH, Haider Hamad M, Ahmad I, Al-Gazally ME, Ziyadullaev S, Sivaraman R, Abed Jawad M, Thaeer Hammid A, Oudaha KH, Karampoor S, Mirzaei R. The emerging role of 27-hydroxycholesterol in cancer development and progression: An update. Int Immunopharmacol 2022; 110:109074. [PMID: 35978522 DOI: 10.1016/j.intimp.2022.109074] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 07/09/2022] [Accepted: 07/17/2022] [Indexed: 02/07/2023]
Abstract
Oxysterols are cholesterol metabolites generated in the liver and other peripheral tissues as a mechanism of removing excess cholesterol. Oxysterols have a wide range of biological functions, including the regulation of sphingolipid metabolism, platelet aggregation, and apoptosis. However, it has been found that metabolites derived from cholesterol play essential functions in cancer development and immunological suppression. In this regard, research indicates that 27-hydroxycholesterol (27-HC) might act as an estrogen, promoting the growth of estrogen receptor (ER) positive breast cancer cells. The capacity of cholesterol to dynamically modulate signaling molecules inside the membrane and particular metabolites serving as signaling molecules are two possible contributory processes. 27-HC is a significant metabolite produced mainly through the CYP27A1 (Cytochrome P450 27A1) enzyme. 27-HC maintains cholesterol balance biologically by promoting cholesterol efflux via the liver X receptor (LXR) and suppressing de novo cholesterol production through the Insulin-induced Genes (INSIGs). It has been demonstrated that 27-HC is able to function as a selective ER regulator. Moreover, enhanced 27-HC production is in favor of the growth of end-stage malignancies in the brain, thyroid organs, and colon, as shown in breast cancer, probably due to pro-survival and pro-inflammatory signaling induced by unbalanced levels of oxysterols. However, the actual role of 27-HC in cancer promotion and progression remains debatable, and many studies are warranted to be performed to unravel the precise function of these molecules. This review article will summarize the latest evidence on the deleterious or beneficial functions of 27-HC in various types of cancer, such as breast cancer, prostate cancer, colon cancer, gastric cancer, ovarian cancer, endometrial cancer, lung cancer, melanoma, glioblastoma, thyroid cancer, adrenocortical cancer, and hepatocellular carcinoma.
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Affiliation(s)
- Saade Abdalkareem Jasim
- Medical Laboratory Techniques Department, Al-maarif University College, Al-anbar-Ramadi, Iraq
| | - Hamzah H Kzar
- Veterinary medicine college, Al-Qasim green University, Al-Qasim, Iraq
| | - Mohammed Haider Hamad
- Medical Laboratory Techniques Department, Al Mustaqbal University college, Babylon, Iraq
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | | | - Shukhrat Ziyadullaev
- Professor, Doctor of Medical Sciences, No.1 Department of Internal Diseases, Vice-rector for Scientific Affairs and Innovations, Samarkand State Medical University, Amir Temur Street 18, Samarkand, Uzbekistan
| | - R Sivaraman
- Department of Mathematics, Institution of Dwaraka Doss Goverdhan Doss Vaishnav College, Arumbakkam, Chennai, University of Madras, Chennai, India
| | | | - Ali Thaeer Hammid
- Computer Engineering Techniques Department, Faculty of Information Technology, Imam Ja'afar Al-Sadiq University, Baghdad, Iraq
| | - Khulood H Oudaha
- Pharmaceutical Chemistry Department, College of Pharmacy, Al-Ayen University Thi-Qar, Iraq
| | - Sajad Karampoor
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Tehran, Iran.
| | - Rasoul Mirzaei
- Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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Abrahams C, Woudberg NJ, Lecour S. Anthracycline-induced cardiotoxicity: targeting high-density lipoproteins to limit the damage? Lipids Health Dis 2022; 21:85. [PMID: 36050733 PMCID: PMC9434835 DOI: 10.1186/s12944-022-01694-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 08/02/2022] [Indexed: 12/30/2022] Open
Abstract
Doxorubicin (DOX) is an anthracycline antibiotic frequently used against a wide range of cancers, including breast cancer. Although the drug is effective as a treatment against cancer, many patients develop heart failure (HF) months to years following their last treatment with DOX. The challenge in preventing DOX-induced cardiotoxicity is that symptoms present after damage has already occurred in the myocardium. Therefore, early biomarkers to assess DOX-induced cardiotoxicity are urgently needed. A better understanding of the mechanisms involved in the toxicity is important as this may facilitate the development of novel early biomarkers or therapeutic approaches. In this review, we discuss the role of high-density lipoprotein (HDL) particles and its components as possible key players in the early development of DOX-induced cardiotoxicity. HDL particles exist in different subclasses which vary in composition and biological functionality. Multiple cardiovascular risk factors are associated with a change in HDL subclasses, resulting in modifications of their composition and physiological functions. There is growing evidence in the literature suggesting that cancer affects HDL subclasses and that healthy HDL particles enriched with sphingosine-1-phosphate (S1P) and apolipoprotein A1 (ApoA1) protect against DOX-induced cardiotoxicity. Here, we therefore discuss associations and relationships between HDL, DOX and cancer and discuss whether assessing HDL subclass/composition/function may be considered as a possible early biomarker to detect DOX-induced cardiotoxicity.
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Affiliation(s)
- Carmelita Abrahams
- Cardioprotection Group, Cape Heart Institute and Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, 7935, South Africa
| | - Nicholas J Woudberg
- Cardioprotection Group, Cape Heart Institute and Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, 7935, South Africa
| | - Sandrine Lecour
- Cardioprotection Group, Cape Heart Institute and Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, 7935, South Africa.
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Decreased serum apolipoprotein A1 level predicts poor prognosis of patients with de novo myelodysplastic syndromes. BMC Cancer 2022; 22:127. [PMID: 35100989 PMCID: PMC8805344 DOI: 10.1186/s12885-022-09248-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 01/27/2022] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Myelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that apolipoproteins A1(ApoA1) are associated with disease risk in many cancer types. However, there still lacks evidence regarding the link between ApoA1 and MDS. This study was designed to investigate the prognostic value of pretreatment ApoA1 levels in MDS patients. METHODS We retrospectively analyzed a cohort of 228 MDS patients to explore the prognostic value of the serum ApoA1 levels at diagnosis. Patients were divided into the high ApoA1 group and the low ApoA1 group. The prognostic significance was determined by univariate and multivariate Cox hazard models. RESULTS MDS patients with low ApoA1 levels had significantly shorter overall survival (OS, P < 0.0001) along with a higher frequency of TP53 mutation (P = 0.002). Based on univariate analysis, age (≥ 60 years), gender (male), lower levels of hemoglobin (< 10 g/dl), HDL (≤0.91 mmol/L), higher bone marrow blast percentage (> 5%), higher IPSS-R scores and poorer karyotype were significantly associated with decreased OS. However, low ApoA1 level did not influence leukemia-free survival (LFS, P = 0.367). Multivariate Cox proportional hazards regression analysis indicated that low ApoA1 level (≤ 1.02 g/L) was also an independent adverse prognostic factor for OS in MDS (P = 0.034). CONCLUSIONS Decreased ApoA1 level predicts a poor prognosis of MDS patients and thus provides a novel evaluation factor for them that is independent of the IPSS-R system.
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Corona G, Di Gregorio E, Vignoli A, Muraro E, Steffan A, Miolo G. 1H-NMR Plasma Lipoproteins Profile Analysis Reveals Lipid Metabolism Alterations in HER2-Positive Breast Cancer Patients. Cancers (Basel) 2021; 13:5845. [PMID: 34830999 PMCID: PMC8616511 DOI: 10.3390/cancers13225845] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/17/2021] [Accepted: 11/20/2021] [Indexed: 01/06/2023] Open
Abstract
The lipid tumour demand may shape the host metabolism adapting the circulating lipids composition to its growth and progression needs. This study aims to exploit the straightforward 1H-NMR lipoproteins analysis to investigate the alterations of the circulating lipoproteins' fractions in HER2-positive breast cancer and their modulations induced by treatments. The baseline 1H-NMR plasma lipoproteins profiles were measured in 43 HER2-positive breast cancer patients and compared with those of 28 healthy women. In a subset of 32 patients, longitudinal measurements were also performed along neoadjuvant chemotherapy, after surgery, adjuvant treatment, and during the two-year follow-up. Differences between groups were assessed by multivariate PLS-DA and by univariate analyses. The diagnostic power of lipoproteins subfractions was assessed by ROC curve, while lipoproteins time changes along interventions were investigated by ANOVA analysis. The PLS-DA model distinguished HER2-positive breast cancer patients from the control group with a sensitivity of 96.4% and specificity of 90.7%, mainly due to the differential levels of VLDLs subfractions that were significantly higher in the patients' group. Neoadjuvant chemotherapy-induced a significant drop in the HDLs after the first three months of treatment and a specific decrease in the HDL-3 and HDL-4 subfractions were found significantly associated with the pathological complete response achievement. These results indicate that HER2-positive breast cancer is characterized by a significant host lipid mobilization that could be useful for diagnostic purposes. Moreover, the lipoproteins profiles alterations induced by the therapeutic interventions could predict the clinical outcome supporting the application of 1H-NMR lipoproteins profiles analysis for longitudinal monitoring of HER2-positive breast cancer in large clinical studies.
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Affiliation(s)
- Giuseppe Corona
- Immunopathology and Cancer Biomarkers Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), 33081 Aviano, Italy; (E.D.G.); (E.M.); (A.S.)
| | - Emanuela Di Gregorio
- Immunopathology and Cancer Biomarkers Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), 33081 Aviano, Italy; (E.D.G.); (E.M.); (A.S.)
- Department of Molecular Science and Nano Systems, Ca’ Foscari University of Venice, Via Torino 155, Venezia Mestre, 30172 Venice, Italy
| | - Alessia Vignoli
- Magnetic Resonance Center (CERM), Department of Chemistry “Ugo Schiff”, University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Italy;
- Consorzio Interuniversitario Risonanze Magnetiche di Metallo Proteine, 50019 Sesto Fiorentino, Italy
| | - Elena Muraro
- Immunopathology and Cancer Biomarkers Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), 33081 Aviano, Italy; (E.D.G.); (E.M.); (A.S.)
| | - Agostino Steffan
- Immunopathology and Cancer Biomarkers Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), 33081 Aviano, Italy; (E.D.G.); (E.M.); (A.S.)
| | - Gianmaria Miolo
- Medical Oncology and Cancer Prevention Unit, IRCCS Centro di Riferimento Oncologico di Aviano (CRO), 33081 Aviano, Italy;
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Luo F, Zeng KM, Cao JX, Zhou T, Lin SX, Ma WJ, Yang YP, Zhang ZH, Lu FT, Huang Y, Zhao HY, Zhang L. Predictive value of a reduction in the level of high-density lipoprotein-cholesterol in patients with non-small-cell lung cancer undergoing radical resection and adjuvant chemotherapy: a retrospective observational study. Lipids Health Dis 2021; 20:109. [PMID: 34544437 PMCID: PMC8454045 DOI: 10.1186/s12944-021-01538-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/31/2021] [Indexed: 12/25/2022] Open
Abstract
Background Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. Methods NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. Results Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). Conclusions Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.
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Affiliation(s)
- Fan Luo
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Kang-Mei Zeng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
| | - Jia-Xin Cao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Ting Zhou
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Su-Xia Lin
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Pathology, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Wen-Juan Ma
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Yun-Peng Yang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Zhong-Han Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Fei-Teng Lu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Yan Huang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China
| | - Hong-Yun Zhao
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Clinical Research, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
| | - Li Zhang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Medical Oncology, Guangdong Esophageal Cancer Institute, Sun Yat- sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
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Wang C, Lin T, Wang X, Yu Z, Zhuge X, Cui W, Wang M, Wang Z, Guo C, Chen X. Low high-density lipoprotein cholesterol levels are associated with malignant intraductal papillary mucinous neoplasms: A multicenter study. Lipids Health Dis 2021; 20:94. [PMID: 34454509 PMCID: PMC8399724 DOI: 10.1186/s12944-021-01523-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 08/16/2021] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Intraductal papillary mucinous neoplasms (IPMNs) can potentially undergo malignant transformation. Studies have shown that high-density lipoprotein cholesterol (HDL-c) was associated with the risk of cancer. In this study, the association between HDL-c and the incidence of malignancy in IPMNs was investigated. MATERIALS AND METHODS 226 patients with histologically proven IPMNs who underwent surgery were included in the present study. Patients were assigned to a training group (n = 151) and validation group (n = 75). Patients' demographic information, clinical data, and histopathological evaluation findings were obtained from medical records. Malignant IPMNs were defined as lesions that showed high grade dysplasia and invasive carcinoma. Logistic regression analyses were used to show the association between HDL-c and malignant IPMNs. Receiver operating characteristic (ROC) curves were generated to analyze predictive performance. RESULTS The prevalence of low HDL-c levels was higher in patients with malignant IPMNs than in those with non-malignant IPMNs (P < 0.01) in both the training group and validation group. The prevalence of malignant IPMNs decreased with an increase in HDL-c levels both in patients with all types of IPMNs, as well as in those with branch-duct IPMNs (BD-IPMNs).Logistic analysis showed that low HDL-c levels were associated with malignant IPMNs (odds ratio (OR) = 20.56, 95 % confidence interval (CI): 2.58-163.64, P < 0.01) in all types of IPMNs and BD-IPMNs (OR = 17.6, 95 %CI: 1.16-268.46, P = 0.02 ).The predictive performance of mural nodules plus low HDL-c levels was higher than that of mural nodules alone or mural nodules plus cyst size for the identification of malignant BD-IPMNs. CONCLUSIONS HDL-c levels may serve a potential biomarker for identifying malignant IPMNs and improve the predictive ability of malignancy in BD-IPMNs.
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Affiliation(s)
- Cheng Wang
- Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan road, 210008, Nanjing, China
| | - Tingting Lin
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, 210029, Nanjing, China
| | - Xinru Wang
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, 210029, Nanjing, China
| | - Zhicheng Yu
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, 210029, Nanjing, China
| | - Xiaoling Zhuge
- Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun road, 310003, Hangzhou, China
| | - Wenjing Cui
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, 210029, Nanjing, China
| | - Miaomiao Wang
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, 210029, Nanjing, China
| | - Zhongqiu Wang
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, 210029, Nanjing, China
| | - Chuangen Guo
- Department of Radiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun road, 310003, Hangzhou, China.
| | - Xiao Chen
- Department of Radiology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong road, 210029, Nanjing, China.
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10
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Dong S, Wang Z, Shen K, Chen X. Metabolic Syndrome and Breast Cancer: Prevalence, Treatment Response, and Prognosis. Front Oncol 2021; 11:629666. [PMID: 33842335 PMCID: PMC8027241 DOI: 10.3389/fonc.2021.629666] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 03/11/2021] [Indexed: 12/13/2022] Open
Abstract
Metabolic syndrome is a type of multifactorial metabolic disease with the presence of at least three factors: obesity, diabetes mellitus, low high-density lipoprotein, hypertriglyceridemia, and hypertension. Recent studies have shown that metabolic syndrome and its related components exert a significant impact on the initiation, progression, treatment response, and prognosis of breast cancer. Metabolic abnormalities not only increase the disease risk and aggravate tumor progression but also lead to unfavorable treatment responses and more treatment side effects. Moreover, biochemical reactions caused by the imbalance of these metabolic components affect both the host general state and organ-specific tumor microenvironment, resulting in increased rates of recurrence and mortality. Therefore, this review discusses the recent advances in the association of metabolic syndrome and breast cancer, providing potential novel therapeutic targets and intervention strategies to improve breast cancer outcome.
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Affiliation(s)
| | | | - Kunwei Shen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaosong Chen
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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11
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Revilla G, Cedó L, Tondo M, Moral A, Pérez JI, Corcoy R, Lerma E, Fuste V, Reddy ST, Blanco-Vaca F, Mato E, Escolà-Gil JC. LDL, HDL and endocrine-related cancer: From pathogenic mechanisms to therapies. Semin Cancer Biol 2020; 73:134-157. [PMID: 33249202 DOI: 10.1016/j.semcancer.2020.11.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Revised: 10/19/2020] [Accepted: 11/16/2020] [Indexed: 02/07/2023]
Abstract
Cholesterol is essential for a variety of functions in endocrine-related cells, including hormone and steroid production. We have reviewed the progress to date in research on the role of the main cholesterol-containing lipoproteins; low-density lipoprotein (LDL) and high-density lipoprotein (HDL), and their impact on intracellular cholesterol homeostasis and carcinogenic pathways in endocrine-related cancers. Neither LDL-cholesterol (LDL-C) nor HDL-cholesterol (HDL-C) was consistently associated with endocrine-related cancer risk. However, preclinical studies showed that LDL receptor plays a critical role in endocrine-related tumor cells, mainly by enhancing circulating LDL-C uptake and modulating tumorigenic signaling pathways. Although scavenger receptor type BI-mediated uptake of HDL could enhance cell proliferation in breast, prostate, and ovarian cancer, these effects may be counteracted by the antioxidant and anti-inflammatory properties of HDL. Moreover, 27-hydroxycholesterol a metabolite of cholesterol promotes tumorigenic processes in breast and epithelial thyroid cancer. Furthermore, statins have been reported to reduce the incidence of breast, prostate, pancreatic, and ovarian cancer in large clinical trials, in part because of their ability to lower cholesterol synthesis. Overall, cholesterol homeostasis deregulation in endocrine-related cancers offers new therapeutic opportunities, but more mechanistic studies are needed to translate the preclinical findings into clinical therapies.
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Affiliation(s)
- Giovanna Revilla
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, C/ Antoni M. Claret 167, 08025 Barcelona, Spain
| | - Lídia Cedó
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain
| | - Mireia Tondo
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Antonio Moral
- Department of General Surgery, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, C/ Antoni M. Claret 167, 08025 Barcelona, Spain
| | - José Ignacio Pérez
- Department of General Surgery, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Rosa Corcoy
- Departament de Medicina, Universitat Autònoma de Barcelona, C/ Antoni M. Claret 167, 08025 Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain; Department of Endocrinology and Nutrition, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Enrique Lerma
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Department of Anatomic Pathology, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Victoria Fuste
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Department of Anatomic Pathology, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain
| | - Srivinasa T Reddy
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA
| | - Francisco Blanco-Vaca
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, C/ Sant Quintí 89, 08041 Barcelona, Spain.
| | - Eugènia Mato
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), C/ Monforte de Lemos 3-5, 28029 Madrid, Spain.
| | - Joan Carles Escolà-Gil
- Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, C/ Sant Quintí 77, 08041 Barcelona Spain.
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12
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Gomaraschi M. Role of Lipoproteins in the Microenvironment of Hormone-Dependent Cancers. Trends Endocrinol Metab 2020; 31:256-268. [PMID: 31837908 DOI: 10.1016/j.tem.2019.11.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 10/28/2019] [Accepted: 11/12/2019] [Indexed: 02/07/2023]
Abstract
The tumor microenvironment (TME) is an attractive target to develop novel strategies for hormone-dependent cancers. Several molecules in the TME can favor tumor development and progression, including lipoproteins. Lipoproteins are taken up by cancer cells, providing them with cholesterol and fatty acids. Cholesterol regulates cell signaling and it is converted into a series of bioactive metabolites, including hormones. The conflicting results of epidemiological and interventional studies suggest that the local availability of lipoproteins in the TME is more relevant for cancer biology than their circulating levels. Thus, reducing lipoprotein uptake and stimulating cell cholesterol efflux to high-density lipoproteins (HDLs) can represent a novel adjuvant strategy for cancer management. HDL-like particles can also act as drug delivery systems for tumor targeting.
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Affiliation(s)
- Monica Gomaraschi
- Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
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13
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Abstract
Excess adiposity is a risk factor for several cancer types. This is likely due to complex mechanisms including alterations in the lipid milieu that plays a pivotal role in multiple aspects of carcinogenesis. Here we consider the direct role of lipids in regulating well-known hallmarks of cancer. Furthermore, we suggest that obesity-associated remodelling of membranes and organelles drives cancer cell proliferation and invasion. Identification of cancer-related lipid-mediated mechanisms amongst the broad metabolic disturbances due to excess adiposity is central to the identification of novel and more efficacious prevention and intervention strategies.
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Affiliation(s)
- J Molendijk
- QIMR Berghofer Medical Research Institute, Herston, Brisbane, 4006, Australia.
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14
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Lipoprotein Drug Delivery Vehicles for Cancer: Rationale and Reason. Int J Mol Sci 2019; 20:ijms20246327. [PMID: 31847457 PMCID: PMC6940806 DOI: 10.3390/ijms20246327] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 11/26/2019] [Accepted: 12/04/2019] [Indexed: 12/11/2022] Open
Abstract
Lipoproteins are a family of naturally occurring macromolecular complexes consisting amphiphilic apoproteins, phospholipids, and neutral lipids. The physiological role of mammalian plasma lipoproteins is to transport their apolar cargo (primarily cholesterol and triglyceride) to their respective destinations through a highly organized ligand-receptor recognition system. Current day synthetic nanoparticle delivery systems attempt to accomplish this task; however, many only manage to achieve limited results. In recent years, many research labs have employed the use of lipoprotein or lipoprotein-like carriers to transport imaging agents or drugs to tumors. The purpose of this review is to highlight the pharmacologic, clinical, and molecular evidence for utilizing lipoprotein-based formulations and discuss their scientific rationale. To accomplish this task, evidence of dynamic drug interactions with circulating plasma lipoproteins are presented. This is followed by epidemiologic and molecular data describing the association between cholesterol and cancer.
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15
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Chen S, Li X, Wen X, Peng S, Xue N, Xing S, Liu Y. Prognostic nomogram integrated baseline serum lipids for patients with non-esophageal squamous cell carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:548. [PMID: 31807530 PMCID: PMC6861798 DOI: 10.21037/atm.2019.09.86] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 08/29/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND Serum lipids have been documented as prognostic biomarkers in several types of cancer, however the prognostic value of serum lipids in non-esophageal squamous cell carcinoma (non-ESCC) is not clear. The purpose of this study was to investigate the prognostic roles of serum lipids in non-ESCC and to establish a novel effective nomogram for overall survival (OS) and disease-free survival (DFS) in patients with non-ESCC. METHODS We retrospectively analyzed the prognostic values of pretreatment serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteinA-I (ApoAI), and apolipoprotein B (ApoB) and three lipid derivatives: atherogenic index [AI: (TC-HDL-C)/HDL-C], THR (TG/HDL-C) and LHR (LDL-C/HDL-C) in non-ESCC patients. Prognostic factors predictive of OS and DFS were determined by univariate and cox hazards analysis, and prognostic nomograms were established. The predictive power of independent prognostic factors was compared adopting time-dependent ROC. Comparisons between the nomograms and traditional TNM staging systems were evaluated using the C-index and decision curve analysis. RESULTS A total of 180 non-ESCC patients were recruited in this prospective study between January 2006 and December 2016. Four (cancer type, TNM stage, TC, and TG) and five (cancer type, TNM stage, TC, TG, and LDL-C) independent prognostic factors were chosen to generate the nomogram for OS and DFS, respectively. Our results showed that the area under curves (AUCs) of cancer type and TG were higher than TNM stage for OS. For DFS, however, AUCs of cancer type, TG and LDL-C were higher than the TNM stage. The C-index of the nomogram for predicting the OS was 0.69, which was significantly higher than that of TNM stage (0.58, P=0.005). In addition, for DFS, the C-index of the nomogram was significantly higher than that of the TNM stage (0.70 vs. 0.60, P=0.001). Furthermore, decision curve analysis showed that the predictive accuracy of the prognostic nomogram for OS and DFS were both higher than the TNM stage. CONCLUSIONS Our study demonstrated that pretreatment of serum lipids based on the prognostic nomogram could be applied to predict the OS and DFS in non-ESCC patients.
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Affiliation(s)
- Shulin Chen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Xiaohui Li
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Xiaoyan Wen
- Department of Urology, The First Municipal Hospital of Guangzhou, Guangzhou 510180, China
| | - Songguo Peng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Ning Xue
- Department of Clinical Laboratory, Affiliated Tumor Hospital of Zhengzhou University, Henan Tumor Hospital, Zhengzhou 450100, China
| | - Shan Xing
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Yijun Liu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
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16
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Revilla G, Pons MDP, Baila-Rueda L, García-León A, Santos D, Cenarro A, Magalhaes M, Blanco RM, Moral A, Ignacio Pérez J, Sabé G, González C, Fuste V, Lerma E, Faria MDS, de Leiva A, Corcoy R, Carles Escolà-Gil J, Mato E. Cholesterol and 27-hydroxycholesterol promote thyroid carcinoma aggressiveness. Sci Rep 2019; 9:10260. [PMID: 31311983 PMCID: PMC6635382 DOI: 10.1038/s41598-019-46727-2] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 07/04/2019] [Indexed: 01/16/2023] Open
Abstract
Cholesterol mediates its proliferative and metastatic effects via the metabolite 27-hydroxycholesterol (27-HC), at least in breast and endometrial cancer. We determined the serum lipoprotein profile, intratumoral cholesterol and 27-HC levels in a cohort of patients with well-differentiated papillary thyroid carcinoma (PTC; low/intermediate and high risk), advanced thyroid cancers (poorly differentiated, PDTC and anaplastic thyroid carcinoma, ATC) and benign thyroid tumors, as well as the expression of genes involved in cholesterol metabolism. We investigated the gene expression profile, cellular proliferation, and migration in Nthy-ori 3.1 and CAL-62 cell lines loaded with human low-density lipoprotein (LDL). Patients with more aggressive tumors (high-risk PTC and PDTC/ATC) showed a decrease in blood LDL cholesterol and apolipoprotein B. These changes were associated with an increase in the expression of the thyroid’s LDL receptor, whereas 3-hydroxy-3-methylglutaryl-CoA reductase and 25-hydroxycholesterol 7-alpha-hydroxylase were downregulated, with an intratumoral increase of the 27-HC metabolite. Furthermore, LDL promoted proliferation in both the Nthy-ori 3.1 and CAL-62 thyroid cellular models, but only in ATC cells was its cellular migration increased significantly. We conclude that cholesterol and intratumoral accumulation of 27-HC promote the aggressive behavior process of PTC. Targeting cholesterol metabolism could be a new therapeutic strategy in thyroid tumors with poor prognosis.
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Affiliation(s)
- Giovanna Revilla
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Departament de Bioquímica, Biologia Molecular i Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Monica de Pablo Pons
- Department of Endocrinology-EDUAB-HSP, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Lucía Baila-Rueda
- Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.,CIBER de Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain
| | - Annabel García-León
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - David Santos
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain
| | - Ana Cenarro
- CIBER de Enfermedades Cardiovasculares, CIBERCV, Madrid, Spain
| | - Marcelo Magalhaes
- Service of Endocrinology, Clinical Research Center (CEPEC), Hospital of the Federal University of Maranhão (HUUFMA), São Luís, Maranhão, Brazil
| | - R M Blanco
- CIBER Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain
| | - Antonio Moral
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of General Surgery-Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Medicine Department, Autonomous University of Barcelona (UAB), Barcelona, Spain
| | - José Ignacio Pérez
- Department of General Surgery-Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Gerard Sabé
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Cintia González
- Department of Endocrinology-EDUAB-HSP, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBER Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain
| | - Victoria Fuste
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of Anatomic Pathology-Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain
| | - Enrique Lerma
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of Anatomic Pathology-Hospital de la Santa Creu i Sant Pau, UAB, Barcelona, Spain
| | - Manuel Dos Santos Faria
- Service of Endocrinology, Clinical Research Center (CEPEC), Hospital of the Federal University of Maranhão (HUUFMA), São Luís, Maranhão, Brazil
| | - Alberto de Leiva
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBER Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain
| | - Rosa Corcoy
- Department of Endocrinology-EDUAB-HSP, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBER Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain.,Medicine Department, Autonomous University of Barcelona (UAB), Barcelona, Spain
| | - Joan Carles Escolà-Gil
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. .,Departament de Bioquímica, Biologia Molecular i Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain. .,CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain.
| | - Eugenia Mato
- Department of Endocrinology-EDUAB-HSP, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. .,CIBER Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain.
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17
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Cedó L, Reddy ST, Mato E, Blanco-Vaca F, Escolà-Gil JC. HDL and LDL: Potential New Players in Breast Cancer Development. J Clin Med 2019; 8:jcm8060853. [PMID: 31208017 PMCID: PMC6616617 DOI: 10.3390/jcm8060853] [Citation(s) in RCA: 97] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 06/11/2019] [Accepted: 06/12/2019] [Indexed: 02/07/2023] Open
Abstract
Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer.
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Affiliation(s)
- Lídia Cedó
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Sant Quintí 77, 08041 Barcelona, Spain.
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Monforte de Lemos 3-5, 28029 Madrid, Spain.
| | - Srinivasa T Reddy
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1736, USA.
| | - Eugènia Mato
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Sant Quintí 77, 08041 Barcelona, Spain.
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Monforte de Lemos 3-5, 28029 Madrid, Spain.
| | - Francisco Blanco-Vaca
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Sant Quintí 77, 08041 Barcelona, Spain.
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Monforte de Lemos 3-5, 28029 Madrid, Spain.
- Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Av. de Can Domènech 737, 08193 Cerdanyola del Vallès, Spain.
| | - Joan Carles Escolà-Gil
- Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Sant Quintí 77, 08041 Barcelona, Spain.
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Monforte de Lemos 3-5, 28029 Madrid, Spain.
- Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Av. de Can Domènech 737, 08193 Cerdanyola del Vallès, Spain.
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18
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Stevanovic M, Vekic J, Bogavac-Stanojevic N, Janac J, Stjepanovic Z, Zeljkovic D, Trifunovic B, Spasojevic-Kalimanovska V, Zeljkovic A. Significance of LDL and HDL subclasses characterization in the assessment of risk for colorectal cancer development. Biochem Med (Zagreb) 2019; 28:030703. [PMID: 30429670 PMCID: PMC6214700 DOI: 10.11613/bm.2018.030713] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 09/04/2018] [Indexed: 12/31/2022] Open
Abstract
Introduction Dyslipidaemia contributes to the occurrence of colorectal cancer (CRC). We hypothesized that qualitative changes of lipoproteins are associated with the risk for CRC development. This study analyses low-density lipoprotein (LDL) and high-density lipoprotein (HDL) diameters, as well as distribution of LDL and HDL subclasses in patients with CRC, with an aim to determine whether advanced lipid testing might be useful in predicting the risk for the onset of this malignancy. Materials and methods This case-control study included 84 patients with newly diagnosed CRC and 92 controls. Gradient gel electrophoresis was applied for separation of lipoprotein subclasses and for LDL and HDL diameters determination. Lipid parameters were measured using routine enzymatic methods. Results Total cholesterol, HDL and LDL-cholesterol were significantly lower in CRC patients compared to controls (4.47 mmol/L vs. 5.63 mmol/L; 0.99 mmol/L vs. 1.27 mmol/L; 2.90 mmol/L vs. 3.66 mmol/L; P < 0.001, respectively). Patients had significantly smaller LDL (25.14 nm vs. 26.92 nm; P < 0.001) and HDL diameters (8.76 nm vs. 10.17 nm; P < 0.001) and greater proportion of small, dense LDL particles (54.0% vs. 52.9%; P = 0.044) than controls. Decreased LDL and HDL diameters were independent predictors of CRC (OR = 0.5, P = 0.001 and OR = 0.5, P = 0.008, respectively), and alongside with age and HDL-cholesterol concentrations formed the optimal cost-effective model, providing adequate discriminative abilities for CRC (AUC = 0.89) and correct patients classification (81%). Conclusions Patients with CRC have decreased LDL and HDL diameters and increased proportion of smaller particles. LDL and HDL diameters determination could be useful in assessing the risk for CRC development.
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Affiliation(s)
- Milica Stevanovic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | - Jelena Vekic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | | | - Jelena Janac
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
| | | | - Dejan Zeljkovic
- Clinic of General Surgery, Military Medical Academy, Belgrade, Serbia
| | - Bratislav Trifunovic
- Clinic of General Surgery, Military Medical Academy, Belgrade, Serbia.,Faculty of Medicine of the Military Medical Academy, University of Defence, Belgrade, Serbia
| | | | - Aleksandra Zeljkovic
- Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
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Isaac-Olivé K, Ocampo-García BE, Aranda-Lara L, Santos-Cuevas CL, Jiménez-Mancilla NP, Luna-Gutiérrez MA, Medina LA, Nagarajan B, Sabnis N, Raut S, Prokai L, Lacko AG. [ 99mTc-HYNIC-N-dodecylamide]: a new hydrophobic tracer for labelling reconstituted high-density lipoproteins (rHDL) for radioimaging. NANOSCALE 2019; 11:541-551. [PMID: 30543234 DOI: 10.1039/c8nr07484d] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Despite the widespread use of nanotechnology in radio-imaging applications, lipoprotein based delivery systems have received only limited attention so far. These studies involve the synthesis of a novel hydrophobic radio-imaging tracer consisting of a hydrazinonicotinic acid (HYNIC)-N-dodecylamide and 99mTc conjugate that can be encapsulated into rHDL nanoparticles (NPs). These rHDL NPs can selectively target the Scavenger Receptor type B1 (SR-B1) that is overexpressed on most cancer cells due to excess demand for cholesterol for membrane biogenesis and thus can target tumors in vivo. We provide details of the tracer synthesis, characterization of the rHDL/tracer complex, in vitro uptake, stability studies and in vivo application of this new radio-imaging approach.
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Affiliation(s)
- Keila Isaac-Olivé
- Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca, 50180 Estado de México, Mexico.
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20
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Samadi S, Ghayour-Mobarhan M, Mohammadpour A, Farjami Z, Tabadkani M, Hosseinnia M, Miri M, Heydari-Majd M, Mehramiz M, Rezayi M, Ferns GA, Avan A. High-density lipoprotein functionality and breast cancer: A potential therapeutic target. J Cell Biochem 2018; 120:5756-5765. [PMID: 30362608 DOI: 10.1002/jcb.27862] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 09/19/2018] [Indexed: 12/16/2022]
Abstract
Breast cancer is a major cause of death globally, and particularly in developed countries. Breast cancer is influenced by cholesterol membrane content, by affecting the signaling pathways modulating cell growth, adherence, and migration. Furthermore, steroid hormones are derived from cholesterol and these play a key role in the pathogenesis of breast cancer. Although most findings have reported an inverse association between serum high-density lipoprotein (HDL)-cholesterol level and the risk of breast cancer, there have been some reports of the opposite, and the association therefore remains unclear. HDL is principally known for participating in reverse cholesterol transport and has an inverse relationship with the cardiovascular risk. HDL is heterogeneous, with particles varying in composition, size, and structure, which can be altered under different circumstances, such as inflammation, aging, and certain diseases. It has also been proposed that HDL functionality might have a bearing on the breast cancer. Owing to the potential role of cholesterol in cancer, its reduction using statins, and particularly as an adjuvant during chemotherapy may be useful in the anticancer treatment, and may also be related to the decline in cancer mortality. Reconstituted HDLs have the ability to release chemotherapeutic drugs inside the cell. As a consequence, this may be a novel way to improve therapeutic targeting for the breast cancer on the basis of detrimental impacts of oxidized HDL on cancer development.
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Affiliation(s)
- Sara Samadi
- Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhooshang Mohammadpour
- Department of Clinical Pharmacy, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Farjami
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahla Tabadkani
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Hosseinnia
- Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehri Miri
- Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Motahareh Heydari-Majd
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehrane Mehramiz
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Rezayi
- Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Brighton, UK
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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21
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Shi H, Huang H, Pu J, Shi D, Ning Y, Dong Y, Han Y, Zarogoulidis P, Bai C. Decreased pretherapy serum apolipoprotein A-I is associated with extent of metastasis and poor prognosis of non-small-cell lung cancer. Onco Targets Ther 2018; 11:6995-7003. [PMID: 30410356 PMCID: PMC6199218 DOI: 10.2147/ott.s170227] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Apolipoprotein A-I (ApoA-I), which recently attracted great attention as an important protein related to the increasing risk of various cancers, is a factor closely related to metabolic diseases such as ardiovascular diseases and atherosclerosis. However, the diagnostic and prognostic value of pretherapy serum ApoA-I levels in non-small-cell lung cancer (NSCLC) patients is still not very clear. Methods In 325 NSCLC patients and 312 healthy controls, pretherapy serum ApoA-I was measured by turbidimetric immunoassay. The association of serum ApoA-I levels with the clinicopathologic characteristics and clinical outcomes of NSCLC patients was analyzed. Receiver-operating characteristic (ROC) curve analysis and univariate and multivariate Cox regression analyses were used to assess the diagnostic and prognostic significance of serum ApoA-I levels. Results Serum ApoA-I levels were obviously decreased in NSCLC patients compared with healthy controls (1.22±0.27 vs 1.46±0.22 g/L, P<0.0001). Pretherapy serum ApoA-I levels were significantly decreased in the NSCLC patients with increased pretherapy C-reactive protein levels (P=0.046), lower albumin serum level (P=0.040), advanced TNM stage (P=0.004), poorer Eastern Cooperative Oncology Group PS: performance status scores (P=0.007), and more than two sites of distant metastasis (P<0.0001). ROC curve showed the optimal cut-off for ApoA-I was 1.26 g/L (Area under ROC curve=0.69, 95% CI=0.54-0.65) with a specificity of 0.75 and a sensitivity of 0.59. The whole cohort was divided into two groups: low ApoA-I levels group (ApoA-I ≤1.26 g/L) consisted of 193 (59.4%) patients and high ApoA-I levels group (ApoA-I >1.26 g/L) consisted of 132 (40.6%) patients. The median survival time of low and high ApoA-I levels patients were 16.45 and 20.90 months, respectively, which indicated a statistically significant difference (χ 2=0.609, P<0.0001) between the two groups. The multivariate analysis results showed that CRP levels (HR=1.273, P=0.038), ApoA-I levels (HR=0.761, P=0.030), Eastern Cooperative Oncology Group performance status (HR=1.486, P=0.016), and extent of metastasis (HR=1.394, P=0.009) were significant independent predictors of favorable overall survival. Conclusion A decreased level of pretherapy ApoA-I was associated with a worse survival in patients with NSCLC. Serum ApoA-I measurement before initial treatment may be a novel and routine biomarker to evaluate for metastasis and predict prognosis for NSCLC patients in daily clinical practice.
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Affiliation(s)
- Hui Shi
- Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, People's Republic of China,
| | - Haidong Huang
- Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, People's Republic of China,
| | - Jin Pu
- Department of Special Clinic, Changhai Hospital, Affiliated to the Second Military Medical University, Shanghai 200433, People's Republic of China
| | - Dongchen Shi
- Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, People's Republic of China,
| | - Yunye Ning
- Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, People's Republic of China,
| | - Yuchao Dong
- Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, People's Republic of China,
| | - Yiping Han
- Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, People's Republic of China,
| | - Paul Zarogoulidis
- Pulmonary Department, Oncology Unit, "Theagenio" Cancer Hospital, Thessaloniki, Greece
| | - Chong Bai
- Department of Respiratory and Critical Care Medicine, Changhai Hospital Affiliated to The Second Military Medical University, Shanghai 200433, People's Republic of China,
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Pirro M, Ricciuti B, Rader DJ, Catapano AL, Sahebkar A, Banach M. High density lipoprotein cholesterol and cancer: Marker or causative? Prog Lipid Res 2018; 71:54-69. [DOI: 10.1016/j.plipres.2018.06.001] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 05/15/2018] [Accepted: 06/02/2018] [Indexed: 12/11/2022]
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Prognostic role of serum total cholesterol and high-density lipoprotein cholesterol in cancer survivors: A systematic review and meta-analysis. Clin Chim Acta 2018; 477:94-104. [DOI: 10.1016/j.cca.2017.11.039] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 11/28/2017] [Accepted: 11/29/2017] [Indexed: 12/18/2022]
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Serum low-density lipoprotein and low-density lipoprotein expression level at diagnosis are favorable prognostic factors in patients with small-cell lung cancer (SCLC). BMC Cancer 2017; 17:269. [PMID: 28410578 PMCID: PMC5391547 DOI: 10.1186/s12885-017-3239-z] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 03/28/2017] [Indexed: 12/13/2022] Open
Abstract
Background Patients with small-cell lung cancer (SCLC) patients demonstrate varied survival outcomes. Previous studies have reported that lipoproteins are associated with prognosis in various cancers; however, the role of low-density lipoprotein (LDL) and low-density lipoprotein- cholesterol (LDLR) in patients with SCLC has not been studied. Methods In this study, the impact of LDL and LDLR on the prognosis of SCLC patients was evaluated. A total of 601 patients with SCLC were retrospectively evaluated, in which 198 patients had adequate tissues for immunohistochemistry, and serum LDL and LDLR expression levels at baseline were tested. X-tile tool, and univariate and multivariate Cox analysis were used to assess the association between LDL, LDLR and overall survival (OS). Results Univariate analysis demonstrated that a lower LDL level was significantly associated with superior OS (P = 0.037). Similarly, LDLR also significantly predicted OS (P = 0.003). Multivariate Cox analyses confirmed that lower LDL and LDLR expression was independent prognostic factors associated with longer OS (P = 0.019 and P = 0.027, respectively). Conclusions This study showed that both LDL and LDLR are prognostic indexes for survival in patients with SCLC. Patients with high LDL or LDLR expression level may benefit from treatment that modulates lipoprotein combined with platinum-based chemotherapy. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3239-z) contains supplementary material, which is available to authorized users.
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25
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Fonseca MIH, da Silva IT, Ferreira SRG. Impact of menopause and diabetes on atherogenic lipid profile: is it worth to analyse lipoprotein subfractions to assess cardiovascular risk in women? Diabetol Metab Syndr 2017; 9:22. [PMID: 28405227 PMCID: PMC5384156 DOI: 10.1186/s13098-017-0221-5] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Accepted: 03/26/2017] [Indexed: 01/13/2023] Open
Abstract
Cardiovascular disease is the leading cause of death in women at advanced age, who are affected a decade later compared to men. Cardiovascular risk factors in women are not properly investigated nor treated and events are frequently lethal. Both menopause and type 2 diabetes substantially increase cardiovascular risk in the female sex, promoting modifications on lipid metabolism and circulating lipoproteins. Lipoprotein subfractions suffer a shift after menopause towards a more atherogenic lipid profile, consisted of hypertriglyceridemia, lower levels of both total high density lipoprotein (HDL) and its subfraction HDL2, but also higher levels of HDL3 and small low-density lipoprotein particles. This review discusses the impact of diabetes and menopause to the lipid profile, challenges in lipoprotein subfractions determination and their potential contribution to the cardiovascular risk assessment in women. It is still unclear whether lipoprotein subfraction changes are a major driver of cardiometabolic risk and which modifications are predominant. Prospective trials with larger samples, methodological standardizations and pharmacological approaches are needed to clarify the role of lipoprotein subfractions determination on cardiovascular risk prediction and intervention planning in postmenopausal women, with or without DM.
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Affiliation(s)
- Marília Izar Helfenstein Fonseca
- Department of Epidemiology, School of Public Health, University of São Paulo, Av. Dr. Arnaldo, 715, São Paulo, SP 01246-904 Brazil
| | - Isis Tande da Silva
- Department of Nutrition, School of Public Health, University of São Paulo, Av. Dr. Arnaldo, 715, São Paulo, SP 01246-904 Brazil
| | - Sandra Roberta G. Ferreira
- Department of Epidemiology, School of Public Health, University of São Paulo, Av. Dr. Arnaldo, 715, São Paulo, SP 01246-904 Brazil
- Department of Nutrition, School of Public Health, University of São Paulo, Av. Dr. Arnaldo, 715, São Paulo, SP 01246-904 Brazil
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26
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Wang Y, Cai X, Zhang S, Cui M, Liu F, Sun B, Zhang W, Zhang X, Ye L. HBXIP up-regulates ACSL1 through activating transcriptional factor Sp1 in breast cancer. Biochem Biophys Res Commun 2017; 484:565-571. [PMID: 28132807 DOI: 10.1016/j.bbrc.2017.01.126] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 01/23/2017] [Indexed: 11/19/2022]
Abstract
The oncoprotein hepatitis B X-interacting protein (HBXIP) results in the dysregulation of lipid metabolism to enhance the development of breast cancer. Acyl-CoA synthetase long-chain family member 1 (ACSL1) is required for thioesterification of long-chain fatty acids into their acyl-CoA derivatives. In this study, we present a hypothesis that HBXIP might be involved in the regulation of ACSL1 in breast cancer. Interestingly, we found that the overexpression of HBXIP was able to up-regulate ACSL1 at the levels of mRNA and protein in a dose-dependent manner in breast cancer cells. Conversely, silencing of HBXIP led to the opposite results. Mechanistically, HBXIP as a coactivator interacted with transcriptional factor Sp1 through binding to the promoter of ACSL1 by ChIP assays analysis, leading to the transcription of ACSL1 in breast cancer cells. Immunohistochemistry staining revealed that the positive rate of ACSL1 was 71.4% (35/49) in clinical breast cancer tissues, HBXIP 79.6% (39/49), in which the positive rate of ACSL1 was 76.9% (30/39) in the HBXIP-positive specimens. But, few positive rate of ACSL1 10% (1/10) was observed in normal breast tissues. The mRNA levels of ACSL1 were significantly higher in clinical breast cancer tissues than those in their corresponding peritumor tissues. The mRNA levels of ACSL1 were positively associated with those of HBXIP in clinical breast cancer tissues. Thus, we conclude that the oncoprotein HBXIP is able to up-regulate ACSL1 through activating the transcriptional factor Sp1 in breast cancer.
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Affiliation(s)
- Yue Wang
- State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Xiaoli Cai
- State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Shuqin Zhang
- State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Ming Cui
- State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Fabao Liu
- State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Baodi Sun
- State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Weiying Zhang
- State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Xiaodong Zhang
- State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China
| | - Lihong Ye
- State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
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Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma. Oncotarget 2016; 6:44037-48. [PMID: 26503474 PMCID: PMC4791285 DOI: 10.18632/oncotarget.5823] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2015] [Accepted: 10/09/2015] [Indexed: 01/05/2023] Open
Abstract
Background We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC). Patients and methods We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I. Results The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis. Conclusion Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.
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Suzumura DN, Schleder JC, Appel MH, Naliwaiko K, Tanhoffer R, Fernandes LC. Fish Oil Supplementation Enhances Pulmonary Strength and Endurance in Women Undergoing Chemotherapy. Nutr Cancer 2016; 68:935-42. [DOI: 10.1080/01635581.2016.1187282] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Babaei Z, Moslemi D, Parsian H, Khafri S, Pouramir M, Mosapour A. Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors. J Egypt Natl Canc Inst 2015; 27:223-9. [PMID: 26462194 DOI: 10.1016/j.jnci.2015.09.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 08/25/2015] [Accepted: 09/03/2015] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Several mechanisms have been proposed to explain the adverse effect of obesity on quality of life among women with breast cancer, including alteration in some inflammatory markers. The aim of this study was to determine the status of serum levels of leptin, IL-6 and CRP in obese, overweight and normal weight breast cancer survivors in order to determine the relationship between inflammatory markers' levels and obesity. MATERIALS AND METHODS This cross-sectional study was done on 75 women with breast cancer, 30 obese, 15 overweight and 30 normal weight patients. Serum leptin, IL-6, CRP, total protein, albumin and lipid profile as well as anthropometric parameters were measured in three groups. RESULTS Serum leptin levels of obese patients were significantly higher than those of overweight and normal weight patients (P<0.05). Higher serum CRP and lower albumin levels were observed in obese patients in comparison with normal weight patients (P<0.05). HDL-C level was significantly different between overweight and normal weight patients (P<0.05). Significant differences in serum IL-6 levels were not observed between the study groups (P>0.05). Moreover, multiple regression analysis showed that leptin was significantly associated with BMI (P<0.001), while albumin was negatively correlated with BMI (P<0.05). CRP levels were significantly correlated with BMI and waist-to-hip ratio (WHR) (P<0.05). CONCLUSIONS In conclusion, high leptin levels and alteration in acute phase proteins in obese patients may exaggerate the inflammation status. As inflammation has the potential to increase the susceptibility of the patients to metastasis development, it is necessary to decline its rate.
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Affiliation(s)
- Zeinab Babaei
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Dariush Moslemi
- Department of Radiation Oncology, Babol University of Medical Sciences, Babol, Iran
| | - Hadi Parsian
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
| | - Soraya Khafri
- Department of Epidemiology, Babol University of Medical Sciences, Babol, Iran
| | - Mahdi Pouramir
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Abbas Mosapour
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
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Cheng T, Dai X, Zhou DL, Lv Y, Miao LY. Correlation of apolipoprotein A-I kinetics with survival and response to first-line platinum-based chemotherapy in advanced non-small cell lung cancer. Med Oncol 2014; 32:407. [PMID: 25465061 DOI: 10.1007/s12032-014-0407-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Accepted: 11/24/2014] [Indexed: 01/05/2023]
Abstract
The aim of this study was to determine whether apolipoprotein A-I (ApoA-I) kinetics predict the overall survival in patients with advanced-stage non-small cell lung cancer (NSCLC) during platinum-based first-line therapy. A total of 125 NSCLC patients from January 2008 to September 2014 were retrospectively reviewed. Serum ApoA-I level was measured at baseline and thereafter at the start of each palliative chemotherapy cycle for all patients. Patients were divided into four groups according to ApoA-I kinetics. Patients whose ApoA-I ≥ 1.01 g/L and never decreased during treatment, patients whose ApoA-I ≥ 1.01 g/L and decreased (ApoA-I < 1.01 g/L) at least one time during treatment, patients whose ApoA-I < 1.01 g/L and normalized (ApoA-I ≥ 1.01) at least one time during treatment, and patients whose ApoA-I < 1.01 g/L and never normalized during treatment were assigned to non-decreased, decreased, normalized, and non-normalized ApoA-I groups, respectively. Overall survival rates were significantly different between the four groups, with 2-year survival rates of 88.6 and 17.5 % for the non-decreased and the decreased ApoA-I groups, respectively, and none survived 2 years later in the normalized and the non-normalized ApoA-I groups. When compared with the non-decreased group, the hazard ratios of death were 0.05, 0.44, and 1.73 in the normalized, decreased, and non-normalized groups, respectively (P < 0.001). Normalization of ApoA-I was associated with a low risk of progression, whereas patients with a decreased level of ApoA-I showed a progression of disease in most cases. ApoA-I can be a novel, widely available biomarker for patients with NSCLC.
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Affiliation(s)
- Ting Cheng
- Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China
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Calip GS, Malone KE, Gralow JR, Stergachis A, Hubbard RA, Boudreau DM. Metabolic syndrome and outcomes following early-stage breast cancer. Breast Cancer Res Treat 2014; 148:363-77. [PMID: 25301086 PMCID: PMC4236717 DOI: 10.1007/s10549-014-3157-6] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Accepted: 09/30/2014] [Indexed: 12/18/2022]
Abstract
The prevalence of risk factors contributing to metabolic syndrome (MetS) is increasing, and numerous components of MetS are associated with increased primary breast cancer (BC) risk. However, less is known about the relationship of MetS to BC outcomes. The aim of this study was to evaluate whether MetS, characterized by increased weight, hypertension, low HDL-cholesterol, high triglycerides, and diabetes or impaired glucose tolerance, is associated with risk of second breast cancer events (SBCE) and BC-specific mortality. Retrospective cohort study of women diagnosed with incident early-stage (I-II) BC between 1990 and 2008, enrolled in an integrated health plan. Outcomes of interest were SBCE, defined as recurrence or second primary BC, and BC-specific mortality. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for time-varying exposure to MetS components while accounting for potential confounders and competing risks. Among 4,216 women in the cohort, 26% had ≥3 MetS components and 13% developed SBCE during median follow-up of 6.3 years. Compared to women with no MetS components, presence of MetS (≥3 components) was associated with increased risk of SBCE (HR = 1.50, 95% CI 1.08-2.07) and BC-specific mortality (HR = 1.65, 95% CI 1.02-2.69). Of the individual components, only increased weight was associated with increased risk of SBCE (HR = 1.26, 95% CI 1.06-1.49). MetS is associated with modestly increased risk of SBCE and BC-specific mortality. Given the growing population of BC survivors, further research in larger and more diverse populations is warranted.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor/metabolism
- Body Mass Index
- Breast Neoplasms/metabolism
- Breast Neoplasms/mortality
- Breast Neoplasms/physiopathology
- Female
- Follow-Up Studies
- Humans
- Immunoenzyme Techniques
- Metabolic Syndrome/complications
- Metabolic Syndrome/metabolism
- Metabolic Syndrome/mortality
- Middle Aged
- Neoplasm Recurrence, Local/etiology
- Neoplasm Recurrence, Local/metabolism
- Neoplasm Recurrence, Local/mortality
- Neoplasm Recurrence, Local/pathology
- Neoplasm Staging
- Neoplasms, Second Primary/etiology
- Neoplasms, Second Primary/metabolism
- Neoplasms, Second Primary/mortality
- Neoplasms, Second Primary/pathology
- Prognosis
- Receptor, ErbB-2/metabolism
- Receptors, Estrogen/metabolism
- Receptors, Progesterone/metabolism
- Retrospective Studies
- Survival Rate
- Young Adult
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Affiliation(s)
- Gregory S Calip
- Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, 833 S. Wood St. M/C 871, Room 287, Chicago, IL, 60612, USA,
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He XD, Wu Q, Liu W, Hong T, Li JJ, Miao RY, Zhao HT. Association of metabolic syndromes and risk factors with ampullary tumors development: A case-control study in China. World J Gastroenterol 2014; 20:9541-9548. [PMID: 25071350 PMCID: PMC4110587 DOI: 10.3748/wjg.v20.i28.9541] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Revised: 02/22/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the risk factors for ampullary adenoma and ampullary cancer.
METHODS: This case-control study included ampullary tumor patients referred to Peking Union Medical College Hospital. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of the same hospital. Data on metabolic syndromes, medical conditions, and family history were collected by retrospective review of the patients’ records and health examination reports, or by interview.
RESULTS: A total of 181 patients and 905 age- and sex-matched controls were enrolled. We found that a history of diabetes, cholecystolithiasis, low-density lipoprotein, and apolipoprotein A were significantly related to ampullary adenomas. Diabetes, cholecystolithiasis, chronic pancreatitis, total cholesterol, high-density lipoprotein, and apolipoprotein A were also significantly related to ampullary cancer.
CONCLUSION: Some metabolic syndrome components and medical conditions are potential risk factors for the development of ampullary tumors. Cholelithiasis, diabetes, and apolipoprotein A may contribute to the malignant transformation of benign ampullary adenomas into ampullary cancer.
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Elevated apolipoprotein A-I levels are associated with favorable prognosis in metastatic nasopharyngeal carcinoma. Med Oncol 2014; 31:80. [PMID: 25023050 DOI: 10.1007/s12032-014-0080-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2014] [Accepted: 06/13/2014] [Indexed: 01/26/2023]
Abstract
The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. Serum lipids and lipoproteins have been reported to be associated with prognosis in some cancers, but it has not been studied in metastatic NPC. The aim of this study was to evaluate whether serum lipid and lipoproteins could predict the prognosis of metastatic NPC patients. Eight hundred and seven patients with metastatic NPC were analyzed retrospectively, and the values of serum lipids and lipoproteins at baseline were retrieved. Receiver operating characteristic curve analysis and univariate and multivariate Cox proportional hazards analyses were used to evaluate the associations of serum lipids and lipoproteins with overall survival (OS). Univariate analysis revealed that higher values of baseline cholesterol (≥4.655 mmol/L), baseline high-density lipoprotein cholesterol (≥0.965 mmol/L), and baseline apolipoprotein A-I (ApoA-I) (≥1.065 g/L) were significantly associated with superior OS (p < 0.001), respectively. Multivariate Cox proportional hazard analysis showed that higher ApoA-I level (vs. lower ApoA-I level, HR 0.64, 95 % CI 0.52-0.80, p < 0.001) was an independent protective factor against progression. In addition, higher body mass index, earlier N stages, single lesion, and absence of liver metastasis were also revealed to be independent protective factors. In conclusion, the elevated baseline ApoA-I level may predict those patients likely to have a favorable OS.
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Abstract
OBJECTIVE The role of metabolic syndrome (MS) and its individual components in postmenopausal breast cancer (PBC) risk is still unclear. We reviewed and summarized epidemiological studies assessing the association of MS with the risk of PBC. METHODS We conducted an electronic search, without restrictions, for articles published before October 31, 2012. Every included study was to report risk estimates with 95% CIs for the association between MS and PBC. Study-specific estimates were pooled using random-effects models. RESULTS Nine articles (with 6,417 cancer cases), all published in English, were included in the meta-analysis. MS was associated with a 52% increase in cancer risk (P < 0.001)-for the most part confined to noncohort studies (109% increased risk); the risk estimates changed little, depending on populations (United States and Europe) and definition of the syndrome (traditional vs nontraditional). The risk estimates for PBC were 1.12 (P = 0.068) for higher values of body mass index/waist circumference, 1.19 (P = 0.005) for hyperglycemia (higher fasting glucose or diabetes), 1.13 (P = 0.027) for higher blood pressure, 1.08 (P = 0.248) for higher triglycerides, and 1.39 (P = 0.008) for lower high-density lipoprotein cholesterol. All these estimates were lower than those associated with MS in the same studies. CONCLUSIONS MS is associated with a moderately increased risk of PBC. No single component explains the risk conveyed by the full syndrome.
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Atypical plasma lipid profile in cancer patients: cause or consequence? Biochimie 2014; 102:9-18. [PMID: 24704108 DOI: 10.1016/j.biochi.2014.03.010] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2013] [Accepted: 03/23/2014] [Indexed: 12/24/2022]
Abstract
The aberrant blood lipoprotein levels in cancer patients are reported to be associated with cancer risk and mortality incidents however, there are several discrepancies in the previous reports. Hence the clinical usefulness of plasma/serum levels in risk stratification of a variety of cancers remains elusive. The present review highlights and compiles findings from different research groups regarding association of plasma lipoprotein levels with the risk of developing various types of cancer. We will discuss some prospective underlying mechanisms for this reported association. In addition to that the potential roles of plasma lipids in promoting carcinogenesis will be conferred.
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Rodrigues Dos Santos C, Fonseca I, Dias S, Mendes de Almeida JC. Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression. BMC Cancer 2014; 14:132. [PMID: 24571647 PMCID: PMC3942620 DOI: 10.1186/1471-2407-14-132] [Citation(s) in RCA: 107] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Accepted: 02/13/2014] [Indexed: 12/21/2022] Open
Abstract
Background Among women, breast cancer (BC) is the leading cancer and the most common cause of cancer-related death between 30 and 69 years. Although lifestyle and diet are considered to have a role in global BC incidence pattern, the specific influence of dyslipidemia in BC onset and progression is not yet completely understood. Methods Fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) was prospectively assessed in 244 women with BC who were enrolled according to pre-set inclusion criteria: diagnosis of non-hereditary invasive ductal carcinoma; selection for surgery as first treatment, and no history of treatment with lipid-lowering or anti-diabetic drugs in the previous year. Pathological and clinical follow-up data were recorded for further inclusion in the statistical analysis. Results Univariate associations show that BC patients with higher levels of LDL-C at diagnosis have tumors that are larger, with higher differentiation grade, higher proliferative rate (assessed by Ki67 immunostaining), are more frequently Her2-neu positive and are diagnosed in more advanced stages. Cox regression model for disease-free survival (DFS), adjusted to tumor T and N stages of TNM classification, and immunohistochemical subtypes, revealed that high LDL-C at diagnosis is associated with poor DFS. At 25 months of follow up, DFS is 12% higher in BC patients within the third LDL-C tertile compared to those in the first tertile. Conclusions This is a prospective study where LDL-C levels, at diagnosis, emerge as a prognostic factor; and this parameter can be useful in the identification and follow-up of high-risk groups. Our results further support a possible role for systemic cholesterol in BC progression and show that cholesterol metabolism may be an important therapeutic target in BC patients.
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Abstract
How aromatase inhibitors affect lipids is of great interest. Compared with tamoxifen, adjuvant anastrozole and letrozole are associated with increased incidences of hypercholesterolemia, while similar data are lacking for exemestane in the adjuvant setting. No significant differences in lipid profiles occurred with extended adjuvant exemestane compared with placebo, but total cholesterol and low-density lipoprotein levels increased significantly above baseline in both groups over 6 months. Likewise, no significant differences in hypercholesterolemia rates occurred between extended adjuvant letrozole and placebo. A lipid substudy further confirmed that letrozole did not significantly alter serum lipids for 36 months compared with placebo. Thus, although aromatase inhibitors lack the lipid-lowering properties of tamoxifen, no significant worsening of lipid levels occurs with their use. Patients would benefit from lifestyle changes and routine monitoring of serum lipids. Breast cancer therapy trials often report serum lipid parameters, but assessing the quality and overall significance of the data can be difficult. Methodology of data collection varies among trials and the concomitant use of lipid-modifying medication is often not reported. This review discusses the current understanding of the influence of lipid levels on cardiovascular risk in women and presents key findings on the effects of adjuvant aromatase inhibitor therapy on lipid profiles.
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Affiliation(s)
- Alain Monnier
- Centre Hospitalier A Boulloche, Oncology Medical Department, 1 Rue du Docteur Flamand, 25209 Montbeliard Cedex, France.
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Vílchez JA, Martínez-Ruiz A, Sancho-Rodríguez N, Martínez-Hernández P, Noguera-Velasco JA. The real role of prediagnostic high-density lipoprotein cholesterol and the cancer risk: a concise review. Eur J Clin Invest 2014; 44:103-14. [PMID: 24111547 DOI: 10.1111/eci.12185] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 09/24/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND In several observational and clinical studies, the association between serum cholesterol levels and cancer is still unsettled although serum total cholesterol has been associated with increased mortality from cancer. Moreover, the importance of abnormal levels of serum lipid components as the main features of dyslipidemia and the risk of individual cancers is unclear. The prevalence of dyslipidemia is increasing worldwide but, the precise aetiology of the link between risk of cancer and the behaviour of lipid profile, prior diagnosis, has yet to be determinated. Low levels of high-density lipoprotein cholesterol (HDL) at baseline of many of the studies analyzed has to be taken into account, and continued low levels of HDL without explanation should be considered by clinicians. AIMS The main aim of this review was to undertake the assessment of the most recent studies implying the lipid profile and cancer risk, and focused on low HDL levels at baseline and follow up, and also analyzing this behaviour on the different cancer types. MATERIAL AND METHODS A literature search was performed to identify publications. The most recent prospective and case-control studies with multivariate Cox models were analyzed and also were considered some recent meta-analyses. RESULTS AND CONCLUSIONS The findings exposed in this review suggest that the association with low HDL levels at baseline of different studies of cancer risk is shared among many types of cancer, and it is mainly linked to obesity and inflammation, suggesting a common pathway.
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Affiliation(s)
- Juan A Vílchez
- Department of Clinical Analysis, University Hospital Virgen de la Arrixaca, Murcia, Spain; Department of Cardiology, University Hospital Virgen de la Arrixaca, Murcia, Spain
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27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Rep 2013; 5:637-45. [PMID: 24210818 DOI: 10.1016/j.celrep.2013.10.006] [Citation(s) in RCA: 280] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 09/11/2013] [Accepted: 10/02/2013] [Indexed: 01/10/2023] Open
Abstract
To date, estrogen is the only known endogenous estrogen receptor (ER) ligand that promotes ER+ breast tumor growth. We report that the cholesterol metabolite 27-hydroxycholesterol (27HC) stimulates MCF-7 cell xenograft growth in mice. More importantly, in ER+ breast cancer patients, 27HC content in normal breast tissue is increased compared to that in cancer-free controls, and tumor 27HC content is further elevated. Increased tumor 27HC is correlated with diminished expression of CYP7B1, the 27HC metabolizing enzyme, and reduced expression of CYP7B1 in tumors is associated with poorer patient survival. Moreover, 27HC is produced by MCF-7 cells, and it stimulates cell-autonomous, ER-dependent, and GDNF-RET-dependent cell proliferation. Thus, 27HC is a locally modulated, nonaromatized ER ligand that promotes ER+ breast tumor growth.
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Hsu MC, Lee KT, Hsiao WC, Wu CH, Sun HY, Lin IL, Young KC. The dyslipidemia-associated SNP on the APOA1/C3/A5 gene cluster predicts post-surgery poor outcome in Taiwanese breast cancer patients: a 10-year follow-up study. BMC Cancer 2013; 13:330. [PMID: 23829168 PMCID: PMC3708770 DOI: 10.1186/1471-2407-13-330] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2013] [Accepted: 06/30/2013] [Indexed: 12/22/2022] Open
Abstract
Background Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression. Methods We analyzed the distribution of 5 selected APOA1/C3/A5 SNPs in recruited Taiwanese breast cancer patients (n=223) and healthy controls (n=162). The association of SNP (APOA1 rs670) showing correlation with breast cancer with baseline and follow-up parameters was further examined. Results APOA1 rs670 A allele carriage was higher in breast cancer patients than controls (59.64% vs. 48.77%, p=0.038). The rs670 A allele carrying patients showed less favorable baseline phenotype with positive lymph nodes (G/A: OR=3.32, 95% CI=1.77-6.20, p<0.001; A/A: OR=2.58, 95% CI=1.05-6.32, p=0.039) and negative hormone receptor expression (A/A: OR=4.85, 95%CI=1.83-12.83, p=0.001) in comparison to G/G carriers. Moreover, rs670 A/A carrying patients had higher risks in both tumor recurrence (HR=3.12, 95% CI=1.29-7.56, p=0.012) and mortality (HR=4.36, 95% CI=1.52-12.47, p=0.006) than patients with no A alleles after adjustments for associated baseline parameters. Furthermore, the prognostic effect of rs670 A/A carriage was most evident in lymph node-negative patients, conferring to the highest risks of recurrence (HR=4.98, 95% CI=1.40-17.70, p=0.013) and mortality (HR=9.87, 95%CI=1.60-60.81, p=0.014) than patients with no A alleles. Conclusions APOA1 rs670 A/A carriage showed poor post-surgery prognosis in Taiwanese lymph node-negative breast cancer patients, whose prognosis were considered better and adjuvant treatment might be less stringent according to currently available assessment protocols. Our findings suggest that APOA1 rs670 indicate a post-surgery risk of breast cancer disease progression, and that carriers of this SNP may benefit from more advanced disease monitoring and therapy regimens than the current regular standards. Furthermore, control of lipid homeostasis might protect APOA1 rs670 minor allele carriers from breast cancer occurrence and progression.
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Affiliation(s)
- Mei-Chi Hsu
- Research Center for Medical Laboratory Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Wu Q, He XD, Yu L, Liu W, Tao LY. The metabolic syndrome and risk factors for biliary tract cancer: a case-control study in China. Asian Pac J Cancer Prev 2013; 13:1963-9. [PMID: 22901155 DOI: 10.7314/apjcp.2012.13.5.1963] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
OBJECTIVES Recent data show that the metabolic syndrome may play a role in several cancers, but the etiology for biliary tract cancer is incompletely defined. The present aim was to evaluate risk factors for biliary tract cancer in China. METHODS A case-control study in which cases were biliary tract cancer patients referred to Peking Union Medical College Hospital (PUMCH). Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on the metabolic syndrome, liver diseases, family history, and history of diabetes and hypertension were collected by retrospective review of the patients' records and health examination reports or by interview. RESULTS A total of 281 patients (102 intrahepatic cholangiocarcinoma (ICC), 86 extrahepatic cholangiocarcinoma (ECC) and 93 gallbladder carcinoma (GC)) and 835 age- and sex-matched controls were enrolled. HBsAg+/anti-HBc+ (P=0.002), history of diabetes (P=0.000), cholelithiasis (P=0.000), TC (P=0.003), and HDL (P=0.000) were significantly related to ICC. Cholelithiasis (P=0.000), Tri (P=0.001), LDL (P=0.000), diabetes (P=0.000), Apo A (P=0.000) and Apo B (P=0.012) were significantly associated with ECC. Diabetes (P=0.017), cholelithiasis (P=0.000) and Apo A (P=0.000) were strongly inversely correlated with GC. CONCLUSION Cholelithiasis, HBV infection and metabolic symptoms may be potential risk factors for the development of biliary tract cancer.
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Affiliation(s)
- Qiao Wu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Tamura T, Inagawa S, Hisakura K, Enomoto T, Ohkohchi N. Evaluation of serum high-density lipoprotein cholesterol levels as a prognostic factor in gastric cancer patients. J Gastroenterol Hepatol 2012; 27:1635-40. [PMID: 22647147 DOI: 10.1111/j.1440-1746.2012.07189.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND AIM Although there are some reports of an adverse effect of low serum high-density lipoprotein cholesterol (HDL-C) levels on gastrointestinal cancers, the specific correlation between serum HDL-C levels and gastric cancer remains unknown. METHODS Preoperative serum HDL-C levels were retrospectively examined in 184 patients who had undergone gastrectomy. The patients who had undergone gastrectomy were divided into two groups: the normal-HDL-C group and the low-HDL-C group. We examined the characteristics and outcomes of these two groups. Univariate and multivariate analyses were performed to investigate the association between serum HDL-C levels and gastric cancer. RESULTS There was no significant difference between the groups in terms of the progression of gastric cancer. In the low-HDL-C group, lymphatic and vascular invasion was significantly increased. The prognosis of the patients in the normal-HDL-C group was significantly better than those in the low-HDL-C group. CONCLUSIONS In this study, a positive correlation between low preoperative serum HDL-C levels and prognosis for gastric cancer was demonstrated. Serum HDL-C level may be a clinical prognostic factor for gastric cancer patients.
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Affiliation(s)
- Takafumi Tamura
- Department of Surgery, Doctoral Program in Clinical Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
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Attner B, Landin-Olsson M, Lithman T, Noreen D, Olsson H. Cancer among patients with diabetes, obesity and abnormal blood lipids: a population-based register study in Sweden. Cancer Causes Control 2012; 23:769-77. [DOI: 10.1007/s10552-012-9946-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Accepted: 03/15/2012] [Indexed: 12/13/2022]
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Watanabe M, Sheriff S, Lewis KB, Cho J, Tinch SL, Balasubramaniam A, Kennedy MA. Metabolic Profiling Comparison of Human Pancreatic Ductal Epithelial Cells and Three Pancreatic Cancer Cell Lines using NMR Based Metabonomics. ACTA ACUST UNITED AC 2012; 3. [PMID: 26609466 PMCID: PMC4655885 DOI: 10.4172/2155-9929.s3-002] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Metabolic profiles of hydrophilic and lipophilic cell extracts from three cancer cell lines, Miapaca-2, Panc-1 and AsPC-1, and a non-cancerous pancreatic ductal epithelial cell line, H6C7, were examined by proton nuclear magnetic resonance spectroscopy. Over twenty five hydrophilic metabolites were identified by principal component and statistical significance analyses as distinguishing the four cell types. Fifteen metabolites were identified with significantly altered concentrations in all cancer cells, e.g. absence of phosphatidylgrycerol and phosphatidylcholine, and increased phosphatidylethanolamine and cholesterols. Altered concentrations of metabolites involved in glycerophospholipid metabolism, lipopolysaccharide and fatty acid biosynthesis indicated differences in cellular membrane composition between non-cancerous and cancer cells. In addition to cancer specific metabolites, several metabolite changes were unique to each cancer cell line. Increased N-acetyl groups in AsPC-1, octanoic acids in Panc-1, and UDP species in Miapaca-2 indicated differences in cellular membrane composition between the cancer cell lines. Induced glutamine metabolism and protein synthesis in cancer cells were indicated by absence of glutamine other metabolites such as acetate, lactate, serine, branched amino acids, and succinate. Knowledge of the specifically altered metabolic pathways identified in these pancreatic cancer cell lines may be useful for identifying new therapeutic targets and studying the effects of potential new therapeutic drugs.
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Affiliation(s)
- Miki Watanabe
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA
| | - Sulaiman Sheriff
- Department of surgery, University of Cincinnati Medical Center, Cincinnati, Ohio, USA
| | - Kenneth B Lewis
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA
| | - Junho Cho
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA
| | - Stuart L Tinch
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA
| | - Ambikaipakan Balasubramaniam
- Department of surgery, University of Cincinnati Medical Center, Cincinnati, Ohio, USA ; Shriners Hospital for Children, Cincinnati, OH 45229, USA ; Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA
| | - Michael A Kennedy
- Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio, USA
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Correlation Between Obesity and High Density Lipoprotein Cholesterol (HDL-C) in Breast Cancer Patients of Southern Rajasthan. Indian J Surg Oncol 2011; 2:118-21. [PMID: 22693403 DOI: 10.1007/s13193-011-0070-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2011] [Accepted: 04/18/2011] [Indexed: 10/18/2022] Open
Abstract
Despite advances in management of breast cancer, etiology is still elusive. Diet, obesity and other life style factors have been implicated in its etiology. We assessed the role of obesity and HDL-C levels in patients with rural background in etiology of breast cancer. To know the relation between obesity and incidence of breast cancer in local population. Also to know serum HDL-C level in breast cancer and its correlation with breast cancer. A nested pilot study of 50 breast cancer patients was done and matched with 50 healthy women as controls. Obesity was measured by weight, height, BMI (Body Mass Index), waist circumference (WC), Hip Circumference (HC), WC/HC ratio, and Serum High Density Lipoprotein Cholesterol (HDL-C) was measured in patients and in controls. There was no significant difference in distribution of weight (p = 0.298), height (p = 0.653), BMI (p = 0.459) and WHR (p = 0.052) among cases and controls. HDL-C level was observed to be significantly lower in cases than control group (p = 0.017).Breast cancer patients of pre menopausal age had significantly low Weight (p = 0.037) and BMI (p = 0.011) than post menopausal patients. In our study population only low HDL-C level had significant correlation with breast cancer and none of the other anthropometric measurements were associated with breast cancer. However, large population based case control and cohort studies are needed to identify low serum HDL-C as an independent predictor of increased risk of breast cancer.
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Sung J, Song YM, Stone J, Lee K, Kim SY. High-density lipoprotein cholesterol, obesity, and mammographic density in Korean women: the Healthy Twin study. J Epidemiol 2010; 21:52-60. [PMID: 21071885 PMCID: PMC3899517 DOI: 10.2188/jea.je20100078] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background High-density lipoprotein cholesterol (HDL-C) is reported to be associated with breast cancer risk. To better understand this association, we examined the relationship between HDL-C and mammographic density, a putative intermediate risk factor for breast cancer. Methods The study subjects were 711 Korean women from the Healthy Twin study. Lipid parameters were assayed enzymatically in fresh sera, and percent dense area (PDA) and absolute dense area were measured from digital mammograms using a computer-assisted method. Results PDA was positively associated with HDL-C in both premenopausal and postmenopausal women in a multivariable-adjusted linear mixed model, but the association did not persist when the model was additionally adjusted for body mass index (BMI). BMI was inversely associated with PDA, and this association did not change after additional adjustment for any lipid parameter. Multivariable-adjusted analysis showed that there were significant additive genetic cross-trait correlations between PDA and both HDL-C (coefficient, 0.175) and triglyceride (coefficient, −0.262). However, those correlations disappeared after additional adjustment for BMI. Conclusions HDL-C alone is unlikely to increase the risk of breast cancer in Korean women, particularly through changes in breast parenchyma that are apparent in mammographic density. BMI should be included in studies using analytical models where mammographic density is used as an intermediate risk factor for breast cancer.
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Affiliation(s)
- Joohon Sung
- Department of Epidemiology and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Korea
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Chen YT, Chen CL, Chen HW, Chung T, Wu CC, Chen CD, Hsu CW, Chen MC, Tsui KH, Chang PL, Chang YS, Yu JS. Discovery of novel bladder cancer biomarkers by comparative urine proteomics using iTRAQ technology. J Proteome Res 2010; 9:5803-15. [PMID: 20806971 DOI: 10.1021/pr100576x] [Citation(s) in RCA: 120] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
A urine sample preparation workflow for the iTRAQ (isobaric tag for relative and absolute quantitation) technique was established. The reproducibility of this platform was evaluated and applied to discover proteins with differential levels between pooled urine samples from nontumor controls and three bladder cancer patient subgroups with different grades/stages (a total of 14 controls and 23 cancer cases in two multiplex iTRAQ runs). Combining the results of two independent clinical sample sets, a total of 638 urine proteins were identified. Among them, 55 proteins consistently showed >2-fold differences in both sample sets. Western blot analyses of individual urine samples confirmed that the levels of apolipoprotein A-I (APOA1), apolipoprotein A-II, heparin cofactor 2 precursor and peroxiredoxin-2 were significantly elevated in bladder cancer urine specimens (n = 25-74). Finally, we quantified APOA1 in a number of urine samples using a commercial ELISA and confirmed again its potential value for diagnosis (n = 126, 94.6% sensitivity and 92.0% specificity at a cutoff value of 11.16 ng/mL) and early detection (n = 71, 83.8% sensitivity and 94.0% specificity). Collectively, our results provide the first iTRAQ-based quantitative profile of bladder cancer urine proteins and represent a valuable resource for the discovery of bladder cancer markers.
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Affiliation(s)
- Yi-Ting Chen
- Molecular Medicine Research Center, Chang Gung University, Taiwan
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48
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Associations between mammographic density and serum and dietary cholesterol. Breast Cancer Res Treat 2010; 125:181-9. [PMID: 20464480 DOI: 10.1007/s10549-010-0927-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2009] [Accepted: 04/28/2010] [Indexed: 12/11/2022]
Abstract
Although high mammographic density is a risk factor for postmenopausal breast cancer, its etiology remains unclear. We examined whether serum and dietary cholesterol, which increase breast cancer risk and are involved in endogenous estrogen formation, were associated with increased mammographic density. We conducted a cross-sectional analysis of 302 healthy, sedentary postmenopausal women, aged 50-74 years, enrolled in the Alberta Physical Activity and Breast Cancer Prevention Trial between 2003 and 2006. In multiple linear regression models, no significant associations were observed between serum lipids and percent density or dense tissue area (Percent density: b (change in square root percent density per unit change in cholesterol level) = -0.06 (95%CI = -0.26 to 0.13); b = 0.06 (95%CI = -0.48 to 0.61); and b = -0.11 (95%CI = -0.33 to 0.10) for total cholesterol, high-, and low-density lipoprotein, respectively; similar results found for dense area). Alcohol consumption modified the association between triglycerides and percent density (>1 drink/day: b = -0.94 (95%CI = -1.79 to -0.10); ≤ 1 drink/day: b = 0.19 (95%CI = -0.12 to 0.50); and no alcohol consumption: b = 0.15 (95%CI = -0.44 to 0.73). We found no evidence indicating any association between dietary and serum cholesterol levels and mammographic density.
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Pasanisi P, Villarini A, Bruno E, Raimondi M, Gargano G, Berrino F. Nutritional advice to breast cancer survivors. Support Care Cancer 2009; 18 Suppl 2:S29-33. [DOI: 10.1007/s00520-009-0701-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2009] [Accepted: 07/07/2009] [Indexed: 02/05/2023]
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Hammad LA, Wu G, Saleh MM, Klouckova I, Dobrolecki LE, Hickey RJ, Schnaper L, Novotny MV, Mechref Y. Elevated levels of hydroxylated phosphocholine lipids in the blood serum of breast cancer patients. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2009; 23:863-876. [PMID: 19224569 DOI: 10.1002/rcm.3947] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
The difference in serum phospholipid content between stage-IV breast cancer patients and disease-free individuals was studied by employing a combination of chemometric statistical analysis tools and mass spectrometry. Chloroform-extracted serum samples were profiled for their lipid class composition and structure using precursor ion, neutral loss, and product ion tandem mass spectrometric (MS/MS) scanning experiments. Changes in the relative abundance of phospholipids in serum as a consequence of cancer progression, measured through electrospray ionization (ESI) mass spectrometry of flow-injected serum samples collected from 25 disease-free individuals and 50 patients diagnosed with stage-IV breast cancer, were statistically evaluated using principal component analysis (PCA), analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis. Lipids whose abundance changed significantly as a consequence of cancer progression were structurally characterized using product ion spectra, and independently quantified using precursor ion scan experiments against an internal standard of known concentration. Phosphocholine lipids that displayed a statistically significant change as a consequence of cancer progression were found to contain an oxidized fatty acid moiety as determined by MS3 experiments.
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Affiliation(s)
- Loubna A Hammad
- METACyt Biochemical Analysis Center, Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA
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