الفهرس 
Breast cancerOnly 14 pages are availabe for public view
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Abstract
Breast cancer (BC) is a frequently diagnosed heterogeneous disease, which represents the primary cause of cancer-related deaths among women. Based on GLOBOCAN 2018 estimates, it affects approximately 25% of all newly diagnosed cancer female patients. Despite recent progress in BC research, this disease still represents a life‐threatening malignancy in women. This is mainly due to cancer-related mortality especially when diagnosed at a higher stage. Despite mammography is the standard method for detecting breast cancer, it may give false results. Moreover, traditional BC markers such as CA15-3 and CEA are found to have insufficient sensitivity and specificity. Therefore, the development of new diagnostic tools and markers becomes an urgent need for detecting BC especially at early stages. Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase known for its crucial role in promoting angiogenesis and facilitating invasion and metastasis in BC. Additionally, MMP-9 has been reported to be associated with poor prognosis in BC. Nevertheless, its utility is not integrated into the clinical management system of BC patients yet. Long non-coding RNAs (lncRNAs) have become one of the most important areas of cancer research. They have been found to participate in the different stages of tumorigenesis. Circulating or cellfree lncRNAs have emerged as promising biomarkers that could improve cancer diagnosis as they proved to be in a stable form in body fluids, besides being non-invasive tools. FAM83H-AS1 and lncRNAATB are two characterized lncRNAs that have been found to be dysregulated in BC. Yet, no studies have explored the diagnostic ability of circulating FAM83H-AS1 and lncRNA-ATB in BC especially at early stages. Our study was conducted to investigate the role of serum FAM83H-AS1, lncRNA-ATB, and MMP-9 as diagnostic markers for BC patients with different stages. In addition, their diagnostic potential was compared with that of the conventional tumor marker CA15-3. Therefore, we measured the levels of FAM83H-AS1, lncRNA-ATB, MMP-9, and CA15-3 in serum of BC patients (30 for each of stages III, III, and IV) and 30 healthy controls. The results revealed that BC samples exhibited significantly increased levels of all measured parameters compared to controls. Besides, levels of serum FAM83H-AS1, MMP-9, and CA15-3 were found to be significantly increased with progressing tumor stage. Analysis of receiver operating characteristic (ROC) curve showed that lncRNA-ATB and MMP-9 were more efficient markers than CA15-3 for diagnosis of BC at all stages and at each stage group (I-II, III, and IV). FAM83H-AS1 was also found to have a good diagnostic performance but not better than CA15-3. Furthermore, our study explored the relationship between all measured parameters and clinicopathological features of BC, including patients’ age, tumor size, lymph node metastasis, secondary metastasis, tumor grade, ER, PR, HER2, ki67 status as well as menopausal status. Serum MMP-9 levels significantly differed depending on patients’ age, whether they are more or less than 50 years old. While other measured parameters showed no significant difference. Patients with larger tumor size exhibited higher levels of FAM83H-AS1, lncRNA-ATB, and CA15-3 than those with smaller tumor size. Serum level of all measured parameters was also significantly increased in patients with higher stage, secondary metastasis, and nodal metastasis, relative to that of their counterparts. Only MMP-9 and CA15-3 were found to have a positive correlation with tumor grade. Regarding immunohistochemical markers of BC, levels of all measured parameters did not vary significantly between ER-positive and -negative groups. While except for MMP-9, all of them showed a significant difference between different PR expression groups, with higher levels being in PR-negative group. Additionally, CA15-3 had a positive correlation with ki67 and HER2 expression. FAM83H-AS1 was also found to be significantly increased in ki67-rich tumors as well as in premenopausal patients, compared to ki67-negative tumors and postmenopausal patients, respectively. While other measured parameters did not show such findings. Moreover, a number of significant correlations between measured parameters was demonstrated in our study, such as a positive correlation between FAM83H-AS1 and CA15-3 as well as between FAM83H-AS1 and MMP-9. Likewise, CA15-3 showed another positive correlation with each of lncRNA-ATB and MMP-9.