A Study on the Role of LPA and ATX in Breast Cancer in Iraq
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Abstract
Breast cancer is the most common malignancy among women and a leading cause of cancer-related mortality. Early detection is crucial for improving treatment outcomes. This study investigates the roles of lysophosphatidic acid (LPA) and autotaxin (ATX) in the early diagnosis of breast cancer among Iraqi women. A case-control study was conducted involving 75 women diagnosed with breast cancer and 75 healthy controls. Blood samples were collected, and biochemical parameters, including LPA and ATX levels, were measured using the ELISA technique. Statistical analyses were performed with SPSS version 24, and receiver operating characteristic (ROC) analysis was used to evaluate diagnostic capabilities. The majority of breast cancer patients were aged 50-59 years (33.3%). Histologically, invasive ductal carcinoma was the most prevalent subtype (82.6%). Biochemical analysis revealed significant differences in alanine aminotransferase, total serum bilirubin, and alkaline phosphatase levels between patients and controls. LPA levels were significantly elevated in the patient group (868.48±142.11 pg/ml) compared to controls (212.01±54.94 pg/ml), while ATX levels were also higher (2252.20±399.46 pg/ml vs. 951.40±209.21 pg/ml). ROC analysis indicated that both LPA and ATX exhibited high diagnostic sensitivity (98%) and specificity (100%). In Iraqi women, elevated serum levels of LPA and ATX may serve as potential diagnostic biomarkers for breast cancer, highlighting their role in disease progression. Further studies are warranted to explore their clinical applications in breast cancer diagnosis and management.
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2. Sasani S, Rashidi Monfared S, Mirzaei AR. Identification of some Echinophora platyloba miRNAs using computational methods and the effect of these miRNAs in the expression of TLN2 and ZNF521 genes in different human body organs. Cell Mol Biomed Rep 2024;4:43-53.
3. Roy S. Membrane-associated RING ubiquitin ligase RNF-121 and advancement of cancer. Cell Mol Biomed Rep 2025;5:80-90.
4. Fatima N, Liu L, Hong S, Ahmed H. Prediction of breast cancer, comparative review of machine learning techniques, and their analysis. IEEE Access 2020;8:150360-76.
5. Saravani K, Saravani S, Dadras F. Investigating attitudinal barriers to breast cancer mammography screening among women in Zabol city. Cell Mol Biomed Rep 2021;1:158-67.
6. Tourang M, Fang L, Zhong Y, Suthar RC. Association between Human Endogenous Retrovirus K gene expression and breast cancer. Cell Mol Biomed Rep 2021;1:7-13.
7. Loibl S, André F, Bachelot T, Barrios C, Bergh J, Burstein H, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up☆. Ann Oncol 2024;35:159-82.
8. Chen J, Li H, Xu W, Guo X. Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer. BMC Gastroenterol 2021;21:58.
9. Karalis T, Poulogiannis G. The Emerging Role of LPA as an Oncometabolite. Cells 2024;13:629.
10. Drosouni A, Panagopoulou M, Aidinis V, Chatzaki E. Autotaxin in breast cancer: role, epigenetic regulation and clinical implications. Cancers 2022;14:5437.
11. Zhang X, Li M, Yin N, Zhang J. The expression regulation and biological function of autotaxin. Cells 2021;10:939.
12. Herr DR, Chew WS, Satish R, Ong WY. Pleotropic roles of autotaxin in the nervous system present opportunities for the development of novel therapeutics for neurological diseases. Mol Neurobiol 2020;57:372-92.
13. Cha YJ, Koo JS. Expression of Autotaxin–Lysophosphatidate Signaling-Related Proteins in Breast Cancer with Adipose Stroma. Int J Mol Sci 2019;20:2102.
14. Novin A, Wali K, Pant A, Liu S, Du W, Liu Y, et al. Oscillatory Hypoxia Can Induce Senescence of Adipose-Derived Mesenchymal Stromal Cells Potentiating Invasive Transformation of Breast Epithelial Cells. Cancers 2024;16:969.
15. Salgado-Polo F, Borza R, Matsoukas MT, Marsais F, Jagerschmidt C, Waeckel L, et al. Autotaxin facilitates selective LPA receptor signaling. Cell Chem Biol 2023;30:69-84. e14.
16. Magkrioti C, Kaffe E, Aidinis V. The role of autotaxin and LPA signaling in embryonic development, pathophysiology and cancer. Int J Mol Sci 2023;24:8325.
17. Quan M, Cui JJ, Feng X, Huang Q. The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer. Tumor Biol 2017;39:1010428317694544.
18. Hameed BH, Al-Rayahi IA, Muhsin SS. Evaluation of Preoperative CA15-3 Level and its Relationship with Clinico-Pathological Characteristics in Primary Breast Cancer Patients. J Tech 2022;4:21-6.
19. Alsabry A, Algabri M, Ahsan AM. Breast Cancer-Risk Factors and Prediction Using Machine-Learning Algorithms and Data Source: A Review of Literature. Sana'a Univ J Appl Sci Technol 2023;1:1-9.
20. Rosa DD, Bines J, Werutsky G, Barrios CH, Cronemberger E, Queiroz GS, et al. The impact of sociodemographic factors and health insurance coverage in the diagnosis and clinicopathological characteristics of breast cancer in Brazil: AMAZONA III study (GBECAM 0115). Breast Cancer Res Treat 2020;183:749-57.
21. Aydiner A, Igci A, Soran A. Breast Disease: Management and Therapies, Volume 2. Springer, 2019.
22. Carleton N, Zou J, Lee S, Mary DJSJ, Li R, Atkinson J, et al. Abstract PO1-14-09: Age-related remodeling of the systemic and breast microenvironment promotes a tumor-permissive locale for ER+ breast cancer in older women. Cancer Res 2024;84:PO1-14-09-PO1-14-09.
23. Houghton LC, Knight JA, Wei Y, Romeo RD, Goldberg M, Andrulis IL, et al. Association of prepubertal and adolescent androgen concentrations with timing of breast development and family history of breast cancer. JAMA Netw Open 2019;2:e190083.
24. Salman RA, AlBairuty GAA, Abdul-Rasheed OF, Salman RA. Decreased catalase activity and glutathione concentration levels in women patients with breast cancer. Ann Trop Med Public Health 2020;23:231-371.
25. Brito-Marcelino A, Duarte-Tavares RJ, Marcelino KB, Silva-Neto JA. Câncer de mama e fatores de risco ocupacionais: revisão integrativa da literatura. Rev Bras Med Trab 2020;18:488-96.
26. Konieczny M, Cipora E, Sygit K, Fal A. Quality of life of women with breast cancer and socio-demographic factors. Asian Pac J Cancer Prev 2020;21:185-93.
27. Yaghjyan L, Austin-Datta RJ, Oh H, Heng YJ, Vellal AD, Sirinukunwattana K, et al. Associations of reproductive breast cancer risk factors with breast tissue composition. Breast Cancer Res 2021;23:1-11.
28. Alwan NA, Tawfeeq FN, Mallah NA. Demographic and clinical profiles of female patients diagnosed with breast cancer in Iraq. J Contemp Med Sci 2019;5:14-9.
29. Olaogun JG, Omotayo JA, Ige JT, Omonisi AE, Akute OO, Aduayi OS. Socio-demographic, pattern of presentation and management outcome of breast cancer in a semi-urban tertiary health institution. Pan Afr Med J 2020;36:363.
30. Volos LI, Dudash AP. Invasive ductal breast carcinoma: morphological features of molecular subtypes. Riga, Latvia: Publishing House “Baltija Publishing” 2021;50-66.
31. Batool AI, Umar I, Idrees F, Rehman FU, Akram A, Habib SS, et al. Evaluation of Oxidative Stress and Clinical Parameters among Female Breast Cancer Patients of Sargodha, Pakistan. Ann Surg Edu 2023;4:1046.
32. Danesh H, Ziamajidi N, Mesbah-Namin SA, Nafisi N, Abbasalipourkabir R. Association between oxidative stress parameters and hematological indices in breast cancer patients. Int J Breast Cancer 2022;2022:1459410.
33. Vítek L. Vztah bilirubinu k nemocem vyvolaným zvýšeným oxidačním stresem. Vnitřní lékařství 2013;59:618-21.
34. Rashid FA, Mahdi S, Abd-Alkader Mahdy S, Salim AT. Effect of obesity on plasma alkaline phosphatase activity in breast cancer. Rep Biochem Mol Biol 2021;10:307-13.
35. Ali AT, Paiker JE, Crowther NJ. The relationship between anthropometry and serum concentrations of alkaline phosphatase isoenzymes, liver enzymes, albumin, and bilirubin. Am J Clin Pathol 2006;126:437-42.
36. Shao Y, Yu Y, He Y, Chen Q, Liu H. Serum ATX as a novel biomarker for breast cancer. Medicine (Baltimore) 2019;98:e14973.
37. Khaled RA, Al-Samarrai RR, Abdel Hamid AZ. Evaluate the Levels of Lysophosphatidic Acid and Lipid Profile in Patients with Breast Cancer. Egypt Acad J Biol Sci C Physiol Mol Biol 2023;15:295-9.
2. Sasani S, Rashidi Monfared S, Mirzaei AR. Identification of some Echinophora platyloba miRNAs using computational methods and the effect of these miRNAs in the expression of TLN2 and ZNF521 genes in different human body organs. Cell Mol Biomed Rep 2024;4:43-53.
3. Roy S. Membrane-associated RING ubiquitin ligase RNF-121 and advancement of cancer. Cell Mol Biomed Rep 2025;5:80-90.
4. Fatima N, Liu L, Hong S, Ahmed H. Prediction of breast cancer, comparative review of machine learning techniques, and their analysis. IEEE Access 2020;8:150360-76.
5. Saravani K, Saravani S, Dadras F. Investigating attitudinal barriers to breast cancer mammography screening among women in Zabol city. Cell Mol Biomed Rep 2021;1:158-67.
6. Tourang M, Fang L, Zhong Y, Suthar RC. Association between Human Endogenous Retrovirus K gene expression and breast cancer. Cell Mol Biomed Rep 2021;1:7-13.
7. Loibl S, André F, Bachelot T, Barrios C, Bergh J, Burstein H, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up☆. Ann Oncol 2024;35:159-82.
8. Chen J, Li H, Xu W, Guo X. Evaluation of serum ATX and LPA as potential diagnostic biomarkers in patients with pancreatic cancer. BMC Gastroenterol 2021;21:58.
9. Karalis T, Poulogiannis G. The Emerging Role of LPA as an Oncometabolite. Cells 2024;13:629.
10. Drosouni A, Panagopoulou M, Aidinis V, Chatzaki E. Autotaxin in breast cancer: role, epigenetic regulation and clinical implications. Cancers 2022;14:5437.
11. Zhang X, Li M, Yin N, Zhang J. The expression regulation and biological function of autotaxin. Cells 2021;10:939.
12. Herr DR, Chew WS, Satish R, Ong WY. Pleotropic roles of autotaxin in the nervous system present opportunities for the development of novel therapeutics for neurological diseases. Mol Neurobiol 2020;57:372-92.
13. Cha YJ, Koo JS. Expression of Autotaxin–Lysophosphatidate Signaling-Related Proteins in Breast Cancer with Adipose Stroma. Int J Mol Sci 2019;20:2102.
14. Novin A, Wali K, Pant A, Liu S, Du W, Liu Y, et al. Oscillatory Hypoxia Can Induce Senescence of Adipose-Derived Mesenchymal Stromal Cells Potentiating Invasive Transformation of Breast Epithelial Cells. Cancers 2024;16:969.
15. Salgado-Polo F, Borza R, Matsoukas MT, Marsais F, Jagerschmidt C, Waeckel L, et al. Autotaxin facilitates selective LPA receptor signaling. Cell Chem Biol 2023;30:69-84. e14.
16. Magkrioti C, Kaffe E, Aidinis V. The role of autotaxin and LPA signaling in embryonic development, pathophysiology and cancer. Int J Mol Sci 2023;24:8325.
17. Quan M, Cui JJ, Feng X, Huang Q. The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer. Tumor Biol 2017;39:1010428317694544.
18. Hameed BH, Al-Rayahi IA, Muhsin SS. Evaluation of Preoperative CA15-3 Level and its Relationship with Clinico-Pathological Characteristics in Primary Breast Cancer Patients. J Tech 2022;4:21-6.
19. Alsabry A, Algabri M, Ahsan AM. Breast Cancer-Risk Factors and Prediction Using Machine-Learning Algorithms and Data Source: A Review of Literature. Sana'a Univ J Appl Sci Technol 2023;1:1-9.
20. Rosa DD, Bines J, Werutsky G, Barrios CH, Cronemberger E, Queiroz GS, et al. The impact of sociodemographic factors and health insurance coverage in the diagnosis and clinicopathological characteristics of breast cancer in Brazil: AMAZONA III study (GBECAM 0115). Breast Cancer Res Treat 2020;183:749-57.
21. Aydiner A, Igci A, Soran A. Breast Disease: Management and Therapies, Volume 2. Springer, 2019.
22. Carleton N, Zou J, Lee S, Mary DJSJ, Li R, Atkinson J, et al. Abstract PO1-14-09: Age-related remodeling of the systemic and breast microenvironment promotes a tumor-permissive locale for ER+ breast cancer in older women. Cancer Res 2024;84:PO1-14-09-PO1-14-09.
23. Houghton LC, Knight JA, Wei Y, Romeo RD, Goldberg M, Andrulis IL, et al. Association of prepubertal and adolescent androgen concentrations with timing of breast development and family history of breast cancer. JAMA Netw Open 2019;2:e190083.
24. Salman RA, AlBairuty GAA, Abdul-Rasheed OF, Salman RA. Decreased catalase activity and glutathione concentration levels in women patients with breast cancer. Ann Trop Med Public Health 2020;23:231-371.
25. Brito-Marcelino A, Duarte-Tavares RJ, Marcelino KB, Silva-Neto JA. Câncer de mama e fatores de risco ocupacionais: revisão integrativa da literatura. Rev Bras Med Trab 2020;18:488-96.
26. Konieczny M, Cipora E, Sygit K, Fal A. Quality of life of women with breast cancer and socio-demographic factors. Asian Pac J Cancer Prev 2020;21:185-93.
27. Yaghjyan L, Austin-Datta RJ, Oh H, Heng YJ, Vellal AD, Sirinukunwattana K, et al. Associations of reproductive breast cancer risk factors with breast tissue composition. Breast Cancer Res 2021;23:1-11.
28. Alwan NA, Tawfeeq FN, Mallah NA. Demographic and clinical profiles of female patients diagnosed with breast cancer in Iraq. J Contemp Med Sci 2019;5:14-9.
29. Olaogun JG, Omotayo JA, Ige JT, Omonisi AE, Akute OO, Aduayi OS. Socio-demographic, pattern of presentation and management outcome of breast cancer in a semi-urban tertiary health institution. Pan Afr Med J 2020;36:363.
30. Volos LI, Dudash AP. Invasive ductal breast carcinoma: morphological features of molecular subtypes. Riga, Latvia: Publishing House “Baltija Publishing” 2021;50-66.
31. Batool AI, Umar I, Idrees F, Rehman FU, Akram A, Habib SS, et al. Evaluation of Oxidative Stress and Clinical Parameters among Female Breast Cancer Patients of Sargodha, Pakistan. Ann Surg Edu 2023;4:1046.
32. Danesh H, Ziamajidi N, Mesbah-Namin SA, Nafisi N, Abbasalipourkabir R. Association between oxidative stress parameters and hematological indices in breast cancer patients. Int J Breast Cancer 2022;2022:1459410.
33. Vítek L. Vztah bilirubinu k nemocem vyvolaným zvýšeným oxidačním stresem. Vnitřní lékařství 2013;59:618-21.
34. Rashid FA, Mahdi S, Abd-Alkader Mahdy S, Salim AT. Effect of obesity on plasma alkaline phosphatase activity in breast cancer. Rep Biochem Mol Biol 2021;10:307-13.
35. Ali AT, Paiker JE, Crowther NJ. The relationship between anthropometry and serum concentrations of alkaline phosphatase isoenzymes, liver enzymes, albumin, and bilirubin. Am J Clin Pathol 2006;126:437-42.
36. Shao Y, Yu Y, He Y, Chen Q, Liu H. Serum ATX as a novel biomarker for breast cancer. Medicine (Baltimore) 2019;98:e14973.
37. Khaled RA, Al-Samarrai RR, Abdel Hamid AZ. Evaluate the Levels of Lysophosphatidic Acid and Lipid Profile in Patients with Breast Cancer. Egypt Acad J Biol Sci C Physiol Mol Biol 2023;15:295-9.
| Files | ||
| Issue | Vol 62 No 5 (2024) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/acta.v62i5.17772 | |
| Keywords | ||
| Autotaxin (ATX) Biomarkers Breast Cancer Iraqi Women Lysophosphatidic Acid (LPA) | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Taha AA, Jassim HS, Hamad WF. A Study on the Role of LPA and ATX in Breast Cancer in Iraq. Acta Med Iran. 2025;62(5):247-253.
