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Evaluation the levels of visfatin,omentin,endothelin-1 and homocysteine in women with breast cancer
Roshna H. Mohammed perozkhan1 , Sahib J. Abdulrahman2
1 Department of Biology, College of education for pure sciences, University of Kirkuk, Kirkuk, Iraq, 2 Professor, Physiology Department, College of education for pure sciences,
University of Kirkuk, Kirkuk, Iraq *Corresponding Author: [email protected]
[email protected] Abstract
This study was carried out at the Oncology Center in Kirkuk-Iraq, the period from october 2020 to march 2021, This study included (70) disease cases for women with breast cancer, their ages ranged between (25-65) years from Kirkuk Oncology & Hematology Center (Kirkuk- Iraq), and this study also included (20) samples of healthy women as a control groups in same ages. and aimed to assess the changes of levels of visfatin, omentin, endothelin-1 and homocysteine features in affected women who suffers from breast cancer in specific areas which is Kirkuk city. The results illustrated a significant increase in P value (P
≤ 0.001) in the concentration of visfatin ,omentin endothelin-1 and homocysteine for women with breast cancer by comparing it to the control group. These results of visfatin in women with breast cancers was 23.16(17.35-33.76) ng/ml compared to control group 4.40(3.05- 5.32)ng/ml . And the result of omentin in patient was 12.55 (10.39-14.91) ng/L compared to healthy control group 3.59 (2.59-5.07) ng/L. The results of endothelin-1 in patient was 30.0(25.26-36.48)ng/L comparison to healthy controlled humans 10.43 (7.22-12.44)ng/L. and the results of homocysteine in patient was 20.99(16.76-31.86)nmol/ml compared to healthy control group 2.77(1.300-6.91) nmol/ml. Conclusion This provides an sign of supporting the important role of stromal-tumor relations with breast cancer.
Key words: Breast cancer,visfatin,omentin,endothelin-1, homocysteine ,cancer . Introduction
The most widespread of gynecological cancer golabel is breast cancer in which effecting more than 2.1 million women every year based on the date of WHO (World Health Organization) (1). 15% death of cancers related to breast cancer in 2018 (WHO, 2018). Due to high percentage of death fighting breast cancer became the priority globally. Genetics, Environment and more other factor might rise the possible danger of breast cancer. Also, it is a fact that once women’s age goes up, their hormones react with high possibility to cell proliferation and very likely to the danger of cancer. Furthermore, the obesity might cause an increase in adipose tissue, and it is the most noticed cause of the caner (2). The possibility risk of breast cancer would be very likely with age because 40% of women with breast cancer are older than 65 years old (3). Other factor also plays roles like obesity in which increase the risk of having breast cancer in women by 25% (4). An endocrine organ, adipose tissue secretes molecules known as adipocytokines that operates within the paracrine, autocrine, and endocrine in which may support the malignant evolution of breast cancer (5). Many academic studies have proved that the adipocytes can work as a mediation the growth, survival, spread and invasion of breast cancer cells (6).
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have indicated that adipocytes mediate the survival, growth, invasion and spread of breast cancer cells (6).
In the related research about the caner, it has been showing that visfatin to be a possible biomarker as it is observed that higher serum visfatin concentration sick people with cancer than in people with no cancer (7) Endothelin-1 is produced by the vascular endothelial cells and is also produced by breast epithelial cells (8) Omentin is a newly identified fatty substance that is highly and selectively expressed in the visceral adipose tissue relative to the subcutaneous adipose tissue (9). Catabolism of the essential amino acid methionine produces Homocysteine which is a thiol-containing amino acid. Homocysteine can be reduced to the cysteine via transculturation rout to the vitamin B6 when methionine is in its highest level (10). The objective of this paper is understanding the changes in the levels of omentin, visfatin, homocysteine and endotheline-1 in the effected women who suffer from breast cancer in a specific geographical area which is in Kirkuk city.
Method and Materials Patient Selection
This study included (70) patient cases of women with breast cancer, their ages ranged between (25-65) years from Kirkuk Oncology & Hematology Center Kirkuk- Iraq, and
included (20) samples of healthy women as a control groups in same ages.
Blood samples
5 ml of venous blood from all included participants. The samples remained at room temperature for 1 hour to clot in the serum separator tubes and centrifuged for 15 minutes at 3000 rpm, the sera were collected and stored at – 20 ͦ C until analysis.
Statistical Analysis
Data was analyzed using GraphPad Prism8 ( Graphpad software, CA,USA) for Microsoft Windows. and were illustrated as median. P less or equal 0.001 was shown as an important statistically. and comparing the statistical valuables among the researched group have conducted by victimization the students for the test in order to do comparison on independent examples in 2 groups while the examples were typically circulated and the Mann-Whitney U test is used to conduct comparison on the example when the examples are not typically circulated. The Receiver Operation Characteristic (ROC) curves was schemed to uncover the cutoff values of the visfatin, omentin and endothelin-1 and to analyze them. Cutoff values were selected at a balance between highest possible sensitivity and specificity.
ELISA Assay
The samples of serum are kept at -20 calicoes visfatin, endothelin-1 and omentin estimaion.
It is estimation in replicas using enzyme-linked immunosorbent assay (ELISA) kit.
Results Visfatin Concentration
The outcome of visfatin’s intensity illustrated that the serum percentage is considerably higher (p ≤ 0.001). in patients 23.16(17.35-33.76) ng/ml compared to control group 4.40(3.05-5.32)ng/ml.
http://annalsofrscb.ro 13990 Fig (1): The picture illustrate the visfatin serum percentage in affected person with breast
cancer associated with the ones who are under controlled humans.
Endothelin-1 Concentration
The outcomes of endothelin-1 concentration (Fig-2) illustrated serum in very high level P≤
0.001 in patient 30.0(25.26-36.48)ng/L comparison to healthy controlled humans 10.43 (7.22- 12.44)ng/L.
Fig(2): The picture illustrate endothelin-1 serum percentage in affected person with breast cancer associated with the ones who are under controlled humans.
Omentin Concentration
The outcomes of omentin concentration (Fig-3) illustrated serum in very high level in the patient P≤ 0.001. 12.55 (10.39-14.91) ng/L compared to healthy control group 3.59 (2.59- 5.07) ng/L.
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Fig(3): The picture illustrate omentin serum percentage in affected person with breast cancer associated with the ones who are under controlled humans.
Homocysteine Concentration
The outcomes of homocysteine concentration (Fig-4) illustrated serum in very high level in the patient P≤ 0.001. 20.99(16.76-31.86)nmol/ml compared to healthy control group 2.77(1.300-6.91) nmol/ml.
Fig(4): The picture illustrate homocysteine serum percentage in affected person with breast cancer associated with the ones who are under controlled humans.
Diagnostic Value of the Visfatin Level
It was examined via analyzing ROC curve (Figure 5) based on sensitivity and specificity of visfatin of 95% CI (1.00-1.00) and Area =1.00.
Diagnostic Value of the Endothelin-1 Level
It was examined via analyzing ROC curve (Figure 5) based on specificity and sensitivity of endothelin-1 of 95 percentage of CI (0.960 to 1.000) and Area =0.984.
http://annalsofrscb.ro 13992 Diagnostic Value of the Omentin Level
It was examined via analyzing ROC curve (Figure 5) based on specificity and sensitivity of omentin of 95 percentage of CI (0.987 to 1.000) and Area =0.996.
Diagnostic Value of the Homocysteine Level
It was examined via analyzing ROC curve (Figure 5) based on sensitivity and specificity of homocysteine of 95% CI (1.000-1.000) and Area =1.000
Fig (5): Receiver-operating characteristic (ROC) of visfatin,omentin,endothelin-1 and homocysteine serum levels among humans with the breast cancer.
Discussion
Visfatin is a novel adipokine and proinflammatory cytokine which is implicated in breast cancer progression (11). Our results illustrated a big growth in the concentration of visfatin, the results of the current study were agreement with a study by Yi-Fen Chiang et al (2019), who found higher serum concentrations of visfatin in women with breast cancer than in the control group, and they attributed the reason for being visfatin plays an important role in the growth and spread of breast cancer and promotes the increase in proliferation breast cancer cells (12).Researches of cancer , shown the visfatin has been a possible biomarker and elevated its serum concentration in sick people with cancer compared to the control group (13,14).
Endothelin-1 is an active peptide that has garnerd much attention over the past decade as an important factor in the development of breast cancer metastasis (15). The results of the current study in breast cancer patients indicate that the level of ET-1 gradually increases as the disease progresses, and this corresponds to (16). ET-1 is also known as a pro-hypertrophic factor (17). Recently, it was found that the endothelin pathway participates in the carcinogenic process by activating the proliferation of cells, as well as the migration of
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invading cells, which helps in the invasion and formation of blood vessels.as advanced studies indicate that ET-1 promotes the progression of breast cancer, and increases quantities of ET-1 is involved in the process of invasion and metastasis (18). Et-1 is formed by the vascular endothelial cells and also by hepatocytes, kidney cells, endometrial cells, neuronal, sertoli cells, and breast epithelial cells (19). Also, endothelin-1 largely excites the evolution of the VEGF which stands for vascular endothelial growth factor, and this is considered the main stimulatory protein for angiogenesis and mitogenesis (20).
Omentin is an adipocytokine which secreted from adipose tissue and may be inversely correlated with obesity and insulin resistance or impaired glucose tolerance (21). The results of study are consistent with the study by Grigorios et al (2020), whom found higher concentrations of omentin in women with breast cancer (22) omentin varies from other lipid cytokines because of its production by the stromal vascular portion of the visceral adipose tissue, and this protein has been shown, through the PI3K/ AKt signaling pathway to promote mesenchymal stem cell proliferation and inhibit apoptosis (23) however, in another study, it showed that omentin was amplified in epicardial adipose tissue but diminished in plasma in coronary heart affected people (24). 2 case- control studies found that higher homocysteine levels were associated with increased breast cancer risk (25,26). In vitro studies indicate that high homocysteine levels are associated with high proliferation rates of cancer cells including breast cancer cells (27,28).
Conclusion
The collected date in this paper gives an indication of the importance of stromal-tumor which interacts with the breast cancer, and importantly this study is utilized an adipocytokine and its impacts on the breast cancer. Women with no breast cancer have lower serum level of omentin, endothelin-1, visfatin and homocysteine comparing it with women who suffers from breast cancer who have higher concentration of serum level. These serum levels can be useful as a screening test as early diagnosis for the women to identify weather they have cancer or not.
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