Association of osteopontin and cyclooxygenase-2 expression with breast cancer subtypes and their use as potential biomarkers

Abstract

Breast cancer is one of the most common malignant tumors among females worldwide and remains a leading cause of cancer-related mortality. Due to the heterogeneous clinical nature of breast cancer, it is necessary to identify new biomarkers that are associated with tumor growth, angiogenesis and metastasis. Osteopontin (OPN) and cyclooxygenase-2 (COX-2) are known to be overexpressed in invasive breast cancer and their overexpression is associated with aggressive histological and clinical features. The present study assessed OPN and COX-2 expression in various subtypes of breast cancer. The expression of OPN and COX-2 was analyzed using immunohistochemistry (IHC) in a cohort of 67 invasive ductal breast carcinoma patients. The statistical analysis was performed using standard statistical software SPSS version 18.0. The associations between OPN and COX-2 and the human epidermal growth factor receptor type 2 (HER2)-overexpressing and non-HER2-overexpressing subtypes were evaluated using the Mann-Whitney U test. The mean OPN level was significantly higher in the HER2-overexpressing subtype compared with the non-HER2-overexpressing subtype. Furthermore, the mean COX-2 expression levels were higher in the HER2-overexpressing subtype compared with the luminal A, luminal B or triple-negative groups. It is well known that carcinomas overexpressing HER2/neu have a worse prognosis than luminal tumors. Hence, it may be hypothesized that an elevated expression of OPN and COX-2 in a HER2-overexpressing subtype may contribute to a more aggressive behavior and be used as diagnostic and prognostic markers in breast cancer.

IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

“…Epidemiologic data have recognized that chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, tobacco smoke, air pollutant, pulmonary infections, and occupational dust are associated with non-small cell lung cancer (NSCLC), suggesting that chronic inflammation plays important roles in the pathogenesis of NSCLC (2). Cyclooxygenase-2 (COX2), a member of the COXs that are responsible for the production of inflammatory mediator prostaglandins, has been identified as a key inflammation-associated molecule in response to cigarette smoking, cytokines, and growth factors, and COX2 is known to promote the initiation and progression of NSCLC as well as other types of human epithelial tumors (3)(4)(5)(6)(7). Interestingly, inhibition of COX2 by nonsteroid anti-inflammatory drugs (NSAID) has been shown to be an effective approach in prevention and therapy of NSCLC and several other types of cancers by both epidemiologic and experimental data (8)(9)(10)(11)(12)(13).…”

Cyclooxygenase-2 expression and its association with vascular endothelial growth factor, microvessel density and clinicopathologic characteristics of colorectal carcinoma

“…VEGF capable of promoting angiogenesis exerts an important effect in the process of genesis, development, metastasis and recurrence of various tumors. In the process of tumor genesis and development, tumor regenerative capillaries capable of providing nutrients for tumor cells and favorable conditions for distal metastasis are the precondition to induce the local growth, infiltration and distal metastasis of malignant tumors, hence, how to inhibit tumor angiogenesis is a new research hotspot at present (Thorat et al, 2013). VEGF, one of the key factors to promote tumor angiogenesis and with the strongest function and highest specificity, can not only promote the proliferation of endothelial cells, but also regulate and participate in angiogenesis (Thorat et al, 2013).…”

“…In the process of tumor genesis and development, tumor regenerative capillaries capable of providing nutrients for tumor cells and favorable conditions for distal metastasis are the precondition to induce the local growth, infiltration and distal metastasis of malignant tumors, hence, how to inhibit tumor angiogenesis is a new research hotspot at present (Thorat et al, 2013). VEGF, one of the key factors to promote tumor angiogenesis and with the strongest function and highest specificity, can not only promote the proliferation of endothelial cells, but also regulate and participate in angiogenesis (Thorat et al, 2013). Due to an intimate association with genesis, development, metastasis and infiltration, it is an important indicator to judge the cancer metastasis and infiltration in clinic (Koyama et al, 2010;Wang et al, 2013).…”

COX-2 expression correlation with invasion in human breast carcinomas and in cell line MDA-MB-231 in vitro

“…Other factors which may be associated with COX-2 in breast cancer, which should be investigated in further studies. It is critical for breast cancer management to identify those biomarkers that would provide those factors potentially curable given the availability of early diagnosis and effective therapeutic protocols, at the time of diagnosis, a reliable prognostic assessment and prediction of treatment response (Thorat et al, 2013;Peng et al, 2013 ).…”

“…The pathological reading was determined for each biopsy slide with an overall pathological diagnosis determined for each subject. The tumor grade was determined according to the modified Bloom-Richardson score (Thorat et al, 2013). The grade was obtained by summing the scores for tubule formation, nuclear pleomorphism, and mitotic count, which were scaled as 1, 2, or 3.…”