|Year : 2019 | Volume
| Issue : 2 | Page : 136-140
Serum protein levels and albumin/globulin ratio in patients with uterus, ovary, and breast tumors compared to healthy women in Kirkuk City
Israa Ghassan Zainal1, Ebaa Ghassan Zainal2
1 Department of Chemistry, College of Science, Kirkuk University, Kirkuk, Iraq
2 Department of Gynecology and Obstetrics, Azadi Teaching Hospital, Kirkuk, Iraq
|Date of Web Publication||17-Jun-2019|
Israa Ghassan Zainal
Department of Chemistry, College of Science, Kirkuk University, Kirkuk
Source of Support: None, Conflict of Interest: None
Background: Gynecological cancer is one of the most serious public health problems in the world with main gynecological cancers, uterus, breast, and ovarian, causing morbidity with severe suffering and a high mortality. Objective: This study aimed to investigate the levels of the total protein (TP), albumin (Alb), globulin (Glo), and Alb/Glo ratio in the female patients with (uterus, ovary, and breast) cancer compared to healthy females. Materials and Methods: This study included 120 females with (28 uteri, 31 ovaries, and 25 breasts) cancer patients and 36 healthy control participants, with age ranges between (20 and 42) years. Results: Alb levels significantly (P ≤ 0.05) decreased in all patient samples except those with uterus cancer who showed significant increase (P ≤ 0.05) compared to healthy participants, and Glo levels significantly (P ≤ 0.05) decreased for uterus and breast cancer samples and nonsignificant (P ≤ 0.05) decrease in patients with ovary cancer compared to healthy participants; finally, the ratio of Alb./Glo. showed significant (P ≤ 0.05) decrease in all patients group except patients with breast cancer showed significant increase (P ≤ 0.05) compared to healthy participants. The results of correlation coefficient indicated that there were significant (P ≤ 0.05) positive correlations between TP and Glo for uterus and breast cancer patients and between TP and Alb for ovary cancer patients. Conclusion: The ratio of Alb/Glo was significantly (P ≤ 0.05) decreased in all patients group except patients with breast cancer who showed significant increase (P ≤ 0.05) compared to healthy participants which could be used in the diagnosis of these patients.
Keywords: Albumin/globulin ratio, breast cancer, ovary cancer, uterus cancer
|How to cite this article:|
Zainal IG, Zainal EG. Serum protein levels and albumin/globulin ratio in patients with uterus, ovary, and breast tumors compared to healthy women in Kirkuk City. Med J Babylon 2019;16:136-40
|How to cite this URL:|
Zainal IG, Zainal EG. Serum protein levels and albumin/globulin ratio in patients with uterus, ovary, and breast tumors compared to healthy women in Kirkuk City. Med J Babylon [serial online] 2019 [cited 2020 Feb 17];16:136-40. Available from: http://www.medjbabylon.org/text.asp?2019/16/2/136/260460
| Introduction|| |
Two major types of proteins present in the serum are “albumin (Alb) and the globulin (Glo).” Alb is the major type of serum protein component. The role of Alb is, however, controversial as yet and Alb use may be based more on custom than on a scientific basis, due to its limited availability and high cost, it is important that the use of Alb is limited to hint for which it is efficacious. Alb was synthesized in abundant amount in the liver, form about 60% of all serum proteins, its water-soluble protein with important functions in regulating the volume of blood by preserving the oncotic pressure (colloid osmotic pressure) of the blood compartment, and also Alb has a function as carrier for many hydrophobic molecules, such as bile salts, steroid hormones, free fatty acids as (apoprotein), unconjugated bilirubin, metals (Ca, Zn, and Cu), and some drugs including phenylbutazone, warfarin, and phenytoin. Serum Glo divided into: alpha (α) and beta (β) Glos are synthesized exclusively in the liver and gamma (γ) Glo is synthesized by B-lymphocytes; all types of Glos are broken down by lthe iver. Gamma Glo presents as a largest proportion from other Glo types. Many confusing factors may effect on the levels of “Alb and Glo” which may influence the accuracy and efficiency in detection of them. A novel prognostic index, the Alb/Glo ratio (AGR), was specified and notified., AGR is a component of them and suggested to be more steady and authoritative than serum Alb or Glo alone., Numerous researchers were promising AGR as tumor marker in diverse types of cancers.,,,, Breast cancer is quite heterogeneous malignant disease with combination “etiological and pathological characteristics.” It is the most common cancer in women and a major public problem of health. Ovarian cancer is the most fatal gynecological cancer and more heterogeneous than breast cancer. Uterine cancer also known as “endometrial cancer” is the most occurring sexual tract malignancy of female in the world. However, according to our knowledge, no study has been conducted to clarify the clinical significance and prognostic value of this marker AGR in “ovarian, uterine, and breast” cancer in Kirkuk city; for this reason, this study was carried out to evaluate and assess the concentration of total protein (TP), Alb, and Glo among women with breast and gynecological cancers (ovary and uterus) compared to healthy participants.
| Materials and Methods|| |
Study area and time
This study was carried out in the Azadi Teaching Hospital, Kirkuk, Iraq, from the period, December 2016 to September 2017.
Collection of blood
A total of 84 women comprising 28, 31, and 25 patients with breast, ovary, and uterus cancer, respectively, age ranges between (20 and 42) years; after being classified by senior surgery and histologically diagnosed (patient suffering from any disease that may interfere with this study were excluded), 36 healthy women with the same age ranges as patients were selected and enrolled into this study. Five milliliters of venous blood was collected from each participant aseptically into a plain container. Samples were allowed to clot, spun at 1500 × g for 10 min, and serum obtained and kept frozen until required for analysis. Ethical approval was given by the Institution Ethical Committee of Azadi Teaching Hospital. Blood samples were collected for testing of TP, Alb, and Glo before starting treatment for patient samples.
Total serum proteins, Alb and Glo, were determined spectrophotometrically using Biuret and bromocresol green methods by Doumas et al. Alb/Glo ratio was also determined by dividing Alb on Glo. All reagents were products of Randox Laboratories UK.
Descriptive statistics were used in analyzing the patient's characteristics and laboratory parameters for each group. In addition, unpaired Student t-test was used to assess group differences, where appropriate. A statistical significant difference was accepted as P < 0.05. All the statistical analyses in this study were made using GraphPad Prism 6.0 program (GraphPad Software, San Diego, CA, USA).
| Results|| |
[Table 1] showed the (mean ± standard deviation) serum “TP, Alb, Glo, and Alb/Glo ratio” to all studied groups.
|Table 1: “Total protein, albumin, and globulin” levels and albumin/globulin ratio in the sera of all studied groups|
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From [Table 1], the results indicated that the levels of TP were significantly (P ≤ 0.05) decreased for all patient samples compared to healthy participants; Alb levels were significantly (P ≤ 0.05) decreased in all patient samples except those with uterus cancer showed significant increase (P ≤ 0.05) compared to healthy participants; Glo levels were significantly (P ≤ 0.05) decreased for breast cancer samples and nonsignificantly (P ≤ 0.05) decrease for uterus cancer, while patients with ovary cancer showed significant increase (P ≤ 0.05) compared to healthy participants; finally, the ratio of Alb/Glo showed significant (P ≤ 0.05) decrease in all patients' group except patients with breast cancer showed significant increase (P ≤ 0.05) compared to healthy participants. [Table 2] and [Figure 1] represent the correlation coefficients and P values for all patient groups and to all parameters.
|Figure 1: Correlation coefficient between serum total protein with (albumin and globulin) and between albumin and globulin|
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The results indicated that there were high positive significant P ≤ 0.05 correlations between TP and Glob for (uterus, breast, and ovary) cancer patients and between TP and Alb. In addition, a negative significant correlation was observed between Alb and Glob in breast patients.
| Discussion|| |
This study compared the TP, Alb, and Glob levels, and the Alb/Glo ratio in patients with (uterus, ovary, and breast) cancers compared to healthy women in Kirkuk city. In the present study, there was significant decrease in TP level for all patient groups compared to healthy participants. Al-Muhtaseb  and Ibrahim et al. found that there was an increase in the TP level in the serum of female patients with breast cancer. Watanabe et al. demonstrated that the circulating rapid turnover protein levels were decreased in advanced stages of ovarian cancer. Al Byati et al. indicated that there was nonsignificant difference (P > 0.05) in TP levels in all patients groups (uterus, ovary, and breast cancer) as compared to healthy participants. Alb and Glo “major components of serum proteins” could be used as a useful prognostic marker and as a predictor of tumor progression and survival, respectively, in cancers, such as “ovarian cancer, gastric cancer, lung cancer, and colorectal cancer.”
The results of this study for Alb and Glo were revealed that there was significant decrease in Alb for ovary and breast cancer patients whereas there was significant increase in uterus cancer patients; the above results were disagreed with Al Byati et al.; they mentioned that there was significant decrease in Alb levels in patients with uterus cancer and nonsignificant difference in breast and ovary cancer patients as compared to normal participants and also found a nonsignificant difference in Glo level in all patients groups and as compared to normal participants. Several studies found that low serum Alb was a negative foreteller of whole survival rate in several tumors  such as colorectal,,, gastric, pancreatic,, hepatocellular, breast,, lung, and ovarian., The decrease in serum Alb level may lead to hypoproteinemia or malnutrition; also, the “survival duration and life quality” of patients with cancer may effect.
The evaluation of both “Alb and Glo” levels in cancer patients instead of one of them is more biologically reliable because the interaction between the two variables. The AGR was supposed as the more “effective, comprehensive, and potential biomarker” for the prognosis of cancer patients due to its easy access and little cost in clinical practice. Diverse studies have notified the relationship between AGR and prognosis in different types of urologic cancers.,,, Liu et al. estimated AGR in patients with gastric cancer and confirmed that AGR was an independent predictive marker of valuation in gastric patients. Liu et al. measured the AGR in patients with heart failure and found that the increase in the levels of AGR indicated a favorable overall survival. The correlation study indicated that for patients with “uterus and ovary” cancer could use the correlation between (TP with Alb and TP with Glo), while for breast cancer patients could use (TP with Glo and Alb with Glo) to follow the disease.
| Conclusion|| |
The ratio of Alb/Glo was significantly decreased in all patients group except patients with breast cancer who showed significant increase compared to healthy participants which could be used in the diagnosis of these patients.
The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki. The study protocol and the subject information and consent form were reviewed and approved by a Local Ethics Committee.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dupree S. Electrophoresis (Methods in Biochemistry). 1st
ed. New Delhi, India: World Technologies, Publishing; 2012.
Boldt J. Use of albumin: An update. Br J Anesthesia 2010;104:276-84.
Higby K, Suiter CR, Phelps JY, Siler-Khodr T, Langer O. Normal values of urinary albumin and total protein excretion during pregnancy. Am J Obstet Gynecol 1994;171:984-9.
Ghazali BA, Abdul-Hussein Al-Taie A, Hameed RJ. Study of the clinical significance of serum albumin level in preeclampsia and in the detection of its severity. Am J Biomed 2014;2:964-74.
Harm S, Schildböck C, Hartmann J. Removal of stabilizers from human serum albumin by adsorbents and dialysis used in blood purification. PLoS One 2018;13:e0191741.
Truman S, Kunjamma MA, Chacko M, Manjula D. Blood pressure, alkaline phosphstase, serum globulin, A: G ratio in pregnant women and matched controls in a population with tapioca as staple food. Int J Med Sci Public Health 2016;5:267-71.
He J, Pan H, Liang W, Xiao D, Chen X, Guo M, et al.
Prognostic effect of albumin-to-globulin ratio in patients with solid tumors: A systematic review and meta-analysis. J Cancer 2017;8:4002-10.
Azab B, Kedia S, Shah N, Vonfrolio S, Lu W, Naboush A, et al.
The value of the pretreatment albumin/globulin ratio in predicting the long-term survival in colorectal cancer. Int J Colorectal Dis 2013;28:1629-36.
Azab BN, Bhatt VR, Vonfrolio S, Bachir R, Rubinshteyn V, Alkaied H, et al.
Value of the pretreatment albumin to globulin ratio in predicting long-term mortality in breast cancer patients. Am J Surg 2013;206:764-70.
Guo HW, Yuan TZ, Chen JX, Zheng Y. Prognostic value of pretreatment albumin/globulin ratio in digestive system cancers: A meta-analysis. PLoS One 2018;13:e0189839.
Lv GY, An L, Sun XD, Hu YL, Sun DW. Pretreatment albumin to globulin ratio can serve as a prognostic marker in human cancers: A meta-analysis. Clin Chim Acta 2018;476:81-91.
Chen WZ, Yu ST, Xie R, Lv YX, Xu DB, Yu JC, et al.
Preoperative albumin/globulin ratio has predictive value for patients with laryngeal squamous cell carcinoma. Oncotarget 2017;8:48240-7.
Deng Y, Pang Q, Miao RC, Chen W, Zhou YY, Bi JB, et al.
Prognostic significance of pretreatment albumin/globulin ratio in patients with hepatocellular carcinoma. Onco Targets Ther 2016;9:5317-28.
Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast cancer: Epidemiology and etiology. Cell Biochem Biophys 2015;72:333-8.
Prat J. FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet 2014;124:1-5.
Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, et al.
Uterine neoplasms, version 1.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2018;16:170-99.
Doumas BT, Bayse DD, Carter RJ, Peters T Jr., Schaffer R. A candidate reference method for determination of total protein in serum. I. Development and validation. Clin Chem 1981;27:1642-50.
Al-Muhtaseb SI. Serum and saliva protein levels in females with breast cancer. Oncol Lett 2014;8:2752-6.
Ibrahim AI, Ahmed SS, Al-Alwan NA. The quantitative levels of serum BRCA1, TP, albumin, and serum PROTEINrotein electrophoresis pattern as a novel biomarkers of breast cancer correlating in the familial breast cancer patients in Iraq. World J Pharm Pharmaceut Sci 2017;6:43-57.
Watanabe T, Shibata M, Nishiyama H, Soeda S, Furukawa S, Gonda K. Serum levels of rapid turnover proteins are decreased and related to systemic inflammation in patients with ovarian cancer. Oncol Lett 2014;7:373-7.
Al Byati RK, Zainal IG, AL-Garawi ZS. Study of total protein and protein profile in patients with (breast, ovary and uterus) cancer. Diyala J 2009;39:1-6.
Ge LN, Wang F. Prognostic significance of preoperative serum albumin in epithelial ovarian cancer patients: A systematic review and dose-response meta-analysis of observational studies. Cancer Manag Res 2018;10:815-25.
Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature. Nutr J 2010;9:69.
Lai CC, You JF, Yeh CY, Chen JS, Tang R, Wang JY, et al.
Low preoperative serum albumin in colon cancer: A risk factor for poor outcome. Int J Colorectal Dis 2011;26:473-81.
Boonpipattanapong T, Chewatanakornkul S. Preoperative carcinoembryonic antigen and albumin in predicting survival in patients with colon and rectal carcinomas. J Clin Gastroenterol 2006;40:592-5.
Sun LC, Chu KS, Cheng SC, Lu CY, Kuo CH, Hsieh JS, et al.
Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment. BMC Cancer 2009;9:288.
Oñate-Ocaña LF, Aiello-Crocifoglio V, Gallardo-Rincón D, Herrera-Goepfert R, Brom-Valladares R, Carrillo JF, et al.
Serum albumin as a significant prognostic factor for patients with gastric carcinoma. Ann Surg Oncol 2007;14:381-9.
Siddiqui A, Heinzerling J, Livingston EH, Huerta S. Predictors of early mortality in veteran patients with pancreatic cancer. Am J Surg 2007;194:362-6.
Ruiz-Tovar J, Martín-Pérez E, Fernández-Contreras ME, Reguero-Callejas ME, Gamallo-Amat C. Impact of preoperative levels of hemoglobin and albumin on the survival of pancreatic carcinoma. Rev Esp Enferm Dig 2010;102:631-6.
Lis CG, Grutsch JF, Vashi PG, Lammersfeld CA. Is serum albumin an independent predictor of survival in patients with breast cancer? JPEN J Parenter Enteral Nutr 2003;27:10-5.
Asher V, Lee J, Bali A. Preoperative serum albumin is an independent prognostic predictor of survival in ovarian cancer. Med Oncol 2012;29:2005-9.
Chi J, Xie Q, Jia J, Liu X, Sun J, Chen J, et al.
Prognostic value of albumin/Globulin ratio in survival and lymph node metastasis in patients with cancer: A systematic review and meta-analysis. J Cancer 2018;9:2341-8.
Koparal MY, Polat F, Çetin S, Bulut EC, Sözen TS. Prognostic role of preoperative albumin to globulin ratio in predicting survival of clear cell renal cell carcinoma. Int Braz J Urol 2018;44:933-46.
Zhang B, Yu W, Zhou LQ, He ZS, Shen C, He Q, et al.
Prognostic significance of preoperative albumin-globulin ratio in patients with upper tract urothelial carcinoma. PLoS One 2015;10:e0144961.
Liu Z, Huang H, Li S, Yu W, Li W, Jin J, et al.
The prognostic value of preoperative serum albumin-globulin ratio for high-grade bladder urothelial carcinoma treated with radical cystectomy: A propensity score-matched analysis. J Cancer Res Ther 2017;13:837-43.
Liu J, Chen S, Geng Q, Liu X, Kong P, Zhan Y, et al.
Prognostic value of pretreatment albumin-globulin ratio in predicting long-term mortality in gastric cancer patients who underwent D2 resection. Onco Targets Ther 2017;10:2155-62.
Li K, Fu W, Bo Y, Zhu Y. Effect of albumin-globulin score and albumin to globulin ratio on survival in patients with heart failure: A retrospective cohort study in China. BMJ Open 2018;8:e022960.
[Table 1], [Table 2]