Association between clinicopathological features of breast cancer with adipocytokine levels and oxidative stress markers before and after chemotherapy

Adipocytokines and markers of oxidative stress have been shown to exhibit potential for detection of advanced stage, HER2/neu status and lymph node metastases in patients with breast cancer, as well as in determining the efficiency of anti-cancer treatments. In the present study, blood concentrations of apelin (APLN), retinol-binding protein 4 (RBP4), 8-hydroxydeoxyguanosine (8-oxo-dG) and total antioxidant capacity (TAC) in women with breast cancer with different clinicopathological features were measured prior to and following adjuvant chemotherapy. The study included 60 women with breast cancer stratified according to tumor grade and size, HER-2/neu expression, and lymph node and hormone receptor status. Blood samples were taken before and after two cycles of adjuvant chemotherapy. None of the clinicopathological features were associated with the baseline concentrations of RBP4, 8-oxo-dG or TAC. An increased baseline concentration of APLN was observed in HER-2/neu positive patients. Moreover, through multivariate logistical regression analysis, APLN was shown to be independently associated with a positive HER/neu status. Chemotherapy treatment did not affect the levels of RBP4 or APLN, or TAC values when assessing all the patients, and when assessing the stratified groups of patients. Only 8-oxo-dG was found to be significantly decreased following drug administration (P=0.0009). This preliminary study demonstrated that APLN is a significant and independent predictor of HER-2/neu positive breast cancer. A significant reduction in 8-oxo-dG levels following chemotherapy may indicate its potential clinical utility in monitoring the effects of chemotherapy in breast cancer patients.

[1]  V. Petrikaitė,et al.  Heterogeneity of breast cancer: the importance of interaction between different tumor cell populations. , 2019, Life sciences.

[2]  Shengrong Sun,et al.  Cancer-associated adipocytes: key players in breast cancer progression , 2019, Journal of Hematology & Oncology.

[3]  Jiayuan Li,et al.  [Association Between Plasma Adiponectin and Risk of Breast Cancer by Molecular Subtypes]. , 2019, Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition.

[4]  Vo Truong Nhu Ngoc,et al.  The Effects of Adipocytes on the Regulation of Breast Cancer in the Tumor Microenvironment: An Update , 2019, Cells.

[5]  J. Zuber,et al.  Apelin inhibition prevents resistance and metastasis associated with anti‐angiogenic therapy , 2019, EMBO molecular medicine.

[6]  T. Hewala,et al.  The clinical significance of serum oxidative stress biomarkers in breast cancer females , 2019, Medical Research Journal.

[7]  Luca Tiano,et al.  Inflammation and Oxidative Stress in an Obese State and the Protective Effects of Gallic Acid , 2018, Nutrients.

[8]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[9]  N. M. Shah,et al.  A qualitative study among breast cancer patients on chemotherapy: experiences and side-effects , 2018, Patient preference and adherence.

[10]  Yongping Liu,et al.  Serum 8-Oxo-dG as a Predictor of Sensitivity and Outcome of Radiotherapy and Chemotherapy of Upper Gastrointestinal Tumours , 2018, Oxidative medicine and cellular longevity.

[11]  Zhenyu Zhang,et al.  Adipokine RBP4 drives ovarian cancer cell migration , 2018, Journal of Ovarian Research.

[12]  Xiang-hui Han,et al.  Adipocytokines and breast cancer. , 2018, Current problems in cancer.

[13]  V. Bruskov,et al.  Exogenous 8-oxo-7,8-dihydro-2′-deoxyguanosine: Biomedical properties, mechanisms of action, and therapeutic potential , 2017, Biochemistry (Moscow).

[14]  A. Ray Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment , 2017, Hormone molecular biology and clinical investigation.

[15]  J. Slingerland,et al.  Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention , 2017, CA: a cancer journal for clinicians.

[16]  G. Frühbeck,et al.  Involvement of the leptin-adiponectin axis in inflammation and oxidative stress in the metabolic syndrome , 2017, Scientific Reports.

[17]  J. Kruk,et al.  Reactive Oxygen and Nitrogen Species in Carcinogenesis: Implications of Oxidative Stress on the Progression and Development of Several Cancer Types. , 2017, Mini reviews in medicinal chemistry.

[18]  Zhenyi Xue,et al.  Adiponectin modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis , 2017, Scientific Reports.

[19]  Li Chen,et al.  The association between obesity related adipokines and risk of breast cancer: a meta-analysis , 2017, Oncotarget.

[20]  C. Touboul,et al.  Supervised Clustering of Adipokines and Hormonal Receptors Predict Prognosis in a Population of Obese Women with Type 1 Endometrial Cancer , 2017, International journal of molecular sciences.

[21]  E. Świętochowska,et al.  Chemotherapy and plasma adipokines level in patients with colorectal cancer. , 2017, Postepy higieny i medycyny doswiadczalnej.

[22]  H. Si,et al.  Elevated Serum Levels of Retinol-Binding Protein 4 Are Associated with Breast Cancer Risk: A Case-Control Study , 2016, PloS one.

[23]  R. Divella,et al.  Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation , 2016, Journal of Cancer.

[24]  M. Akyol,et al.  Serum apelin levels and body composition changes in breast cancer patients treated with an aromatase inhibitor. , 2016, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[25]  Hongwei Yu,et al.  Tumor apelin, not serum apelin, is associated with the clinical features and prognosis of gastric cancer , 2016, BMC Cancer.

[26]  L. Berstein,et al.  Serum Levels of 8-Hydroxy-2’-Deoxyguanosine DNA in Patients with Breast Cancer and Endometrial Cancer with and without Diabetes Mellitus , 2016, Bulletin of Experimental Biology and Medicine.

[27]  I. Aoki,et al.  Overproduction of reactive oxygen species - obligatory or not for induction of apoptosis by anticancer drugs , 2016, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[28]  V. Víctor,et al.  Role of ROS and RNS Sources in Physiological and Pathological Conditions , 2016, Oxidative medicine and cellular longevity.

[29]  Shuang-Yu Lv,et al.  Apelin/APJ system and cancer. , 2016, Clinica chimica acta; international journal of clinical chemistry.

[30]  T. Coşkun,et al.  Effect of oncological treatment on serum adipocytokine levels in patients with stage II-III breast cancer. , 2016, Molecular and clinical oncology.

[31]  F. Casanueva,et al.  A role for novel adipose tissue‐secreted factors in obesity‐related carcinogenesis , 2016, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[32]  R. Ahima,et al.  Obesity and Breast Cancer: A Complex Relationship , 2016, Current Surgery Reports.

[33]  J. Jakić-Razumović,et al.  Breast Cancer Molecular Subtypes and Oxidative DNA Damage , 2015, Applied immunohistochemistry & molecular morphology : AIMM.

[34]  N. A. E. Moneim,et al.  Serum Adipocytokines (Visfatin and Resistin): New Biomarkers of Breast Carcinogenesis , 2015 .

[35]  K. Lam,et al.  Obesity, adipokines and cancer: an update , 2015, Clinical endocrinology.

[36]  M. Xia,et al.  Retinol binding protein 4 induces mitochondrial dysfunction and vascular oxidative damage. , 2015, Atherosclerosis.

[37]  K. Roszkowski,et al.  Potential survival markers in cancer patients undergoing chemotherapy , 2015, Clinical and Experimental Medicine.

[38]  G. Altavilla,et al.  Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation , 2015, Clinical and Experimental Medicine.

[39]  Y. Maehara,et al.  The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. , 2014, Anticancer research.

[40]  W. Berger,et al.  Apelin promotes lymphangiogenesis and lymph node metastasis , 2014, Oncotarget.

[41]  C. Poh,et al.  Apelin Attenuates Oxidative Stress in Human Adipocytes* , 2013, The Journal of Biological Chemistry.

[42]  J. Abbruzzese,et al.  Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations , 2013, Cancer & Metabolism.

[43]  D. Murawa,et al.  Total antioxidant status in plasma of breast cancer patients in relation to ERβ expression , 2013, Contemporary oncology.

[44]  G. De Pergola,et al.  Obesity as a Major Risk Factor for Cancer , 2013, Journal of obesity.

[45]  C. Giordano,et al.  Leptin increases HER2 protein levels through a STAT3‐mediated up‐regulation of Hsp90 in breast cancer cells , 2013, Molecular oncology.

[46]  W. Rajendra,et al.  Serum selenium concentration and antioxidant activity in cervical cancer patients before and after treatment. , 2013, Experimental oncology.

[47]  J. Quiles,et al.  Oxidative stress status in metastatic breast cancer patients receiving palliative chemotherapy and its impact on survival rates , 2012, Free radical research.

[48]  K. Roszkowski,et al.  Oxidative damage DNA: 8-oxoGua and 8-oxodG as molecular markers of cancer , 2011, Medical science monitor : international medical journal of experimental and clinical research.

[49]  C. Boonla,et al.  Elevated urinary total sialic acid and increased oxidative stress in patients with bladder cancer , 2010 .

[50]  A. Jukkola-Vuorinen,et al.  8-Hydroxydeoxyguanosine: a new potential independent prognostic factor in breast cancer , 2010, British Journal of Cancer.

[51]  T. Akçay,et al.  DNA Oxidation and Antioxidant Status in Breast Cancer , 2009, Journal of Investigative Medicine.

[52]  H. Alho,et al.  Impact of radiotherapy and chemotherapy on biomarkers of oxidative DNA damage in lung cancer patients. , 2009, Clinical biochemistry.

[53]  A. Cecchini,et al.  Breast Cancer and Oxidative Stress in Chemotherapy , 2009 .

[54]  A. Giordano,et al.  Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis , 2008, BMC Cancer.

[55]  H. Nagawa,et al.  Leptin augments proliferation of breast cancer cells via transactivation of HER2. , 2008, The Journal of surgical research.

[56]  D. Murawa,et al.  Plasma total antioxidant status in breast cancer women in relation to lymph node involvement and HER-2/neu expression , 2007 .

[57]  Li Zhang,et al.  Adipocytokines and breast cancer risk. , 2007, Chinese medical journal.

[58]  T. Mizoue,et al.  Body mass index and oxidative DNA damage: A longitudinal study , 2007, Cancer science.

[59]  Xuan Yang,et al.  Serum levels of leptin, insulin, and lipids in relation to breast cancer in China , 2005, Endocrine.

[60]  U. Smith,et al.  Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. , 2006, The New England journal of medicine.

[61]  M. Hou,et al.  Serum adiponectin and leptin levels in Taiwanese breast cancer patients. , 2006, Cancer letters.

[62]  H. Ahsan,et al.  Reactive oxygen species: role in the development of cancer and various chronic conditions , 2006, Journal of carcinogenesis.

[63]  T. Mizoue,et al.  Leanness, Smoking, and Enhanced Oxidative DNA Damage , 2006, Cancer Epidemiology Biomarkers & Prevention.

[64]  A. Davenport,et al.  Emerging roles of apelin in biology and medicine. , 2005, Pharmacology & therapeutics.

[65]  K. Conklin Chemotherapy-Associated Oxidative Stress: Impact on Chemotherapeutic Effectiveness , 2004, Integrative cancer therapies.

[66]  J. Klaunig,et al.  The role of oxidative stress in carcinogenesis. , 2004, Annual review of pharmacology and toxicology.

[67]  S. Hinuma,et al.  Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. , 1998, Biochemical and biophysical research communications.

[68]  T. Basu,et al.  Biochemical Status of Vitamin A in Patients with Malignant and Benign Breast Disease. , 1992 .