Search

Background and Objectives: breast cancer remains the most common health burden affecting females worldwide. Despite developments in breast cancer diagnostic approaches and treatment strategies, the clinical management of metastatic breast cancer remains challenging. Thus, there is a need to identify new biomarkers and novel drug targets for breast cancer diagnosis and therapy. Recently, aberrant glypican-3 (GPC3) expression in cancers has gained considerable interest in cancer research. The studies, however, have yielded contradictory results about GPC3 expression in breast cancer. Therefore, the current study aims to analyse GPC3 expression across a large panel of different breast cancer subtypes. Materials and Methods: GPC3 expression was immunohistochemically evaluated in 230 breast cancer patients along with eight normal tissues and its associations to clinical and demographic characteristics, as well as immunohistochemical biomarkers for breast cancer. Moreover, a public database consisting of breast cancer patients' survival data and GPC3 gene expression information was used to assess the prognostic value of GPC3 in the survival of breast cancer patients. Results: GPC3 expression was only characterised in 7.5% of different histological breast cancer subtypes. None of the normal breast tissues displayed GPC3 expression. Interestingly, all cases of Paget's disease, as well as 42.9% of intraductal and 16.7% of mucinous carcinomas were found to have GPC3 expression, where it was able to significantly discriminate Paget's disease and intraductal carcinoma from other breast cancer subtypes. Importantly, GPC3 expression was found more often in tumours that tested positive for the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), indicating more favourable histological subtypes of breast cancer. Consequently, longer relapse-free survival (RFS) was significantly correlated with higher GPC3 mRNA expression. Conclusions: Our study proposes that GPC3 is a promising breast cancer subtype-specific biomarker. Moreover, GPC3 may have the potential to be a molecular target for the development of new therapeutics for specific subtypes of breast cancer. [ABSTRACT FROM AUTHOR]

Background and Objective: Ovarian cancer is a leading cause of death in females. Since its treatment is challenging and causes severe side effects, novel therapies are urgently needed. One of the potential enzymes implicated in the progression of cancers is Cytochrome 4Z1 (CYP4Z1). Its expression in ovarian cancer remains unknown. Therefore, the current study aims to assess CYP4Z1 expression in different subtypes of ovarian cancers. Materials and Methods: Immunohistochemistry was used to characterize CYP4Z1 expression in 192 cases of ovarian cancers along with eight normal ovarian tissues. The enzyme's association with various clinicopathological characteristics and survival was determined. Results: CYP4Z1 was strongly expressed in 79% of ovarian cancers, compared to negative expression in normal ovarian samples. Importantly, significantly high CYP4Z1 expres-sion was determined in patients with advanced-stage cancer and a high depth of invasion (p < 0.05). Surprisingly, CYP4Z1 expression was significantly associated with a low patient survival rate. Univariate analysis revealed that patient survival was strongly associated with CYP4Z1 expression, tumor stage, depth of invasion, and lymph node metastasis (p < 0.05). Multivariate analysis showed that only CYP4Z1 expression was significantly associated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is correlated with shorter patient survival and has been identified as an independent indicator of a poor prognosis for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Colon cancer is a leading cause of mortality worldwide. It has a relatively poor prognosis; therefore, new therapies are needed. One of the tumour-related enzymes that has gained considerable interest is CYP4Z1. This enzyme has been expressed in many tumours and has been hypothesized as a potential biomarker or target for novel anticancer therapies. Patients and Methods: CYP4Z1 overexpression was immunohistochemically examined in a large panel of colon tissue types including normal, benign, primary and metastatic ones, and the enzyme's relation to histopathological features and patient survival was evaluated. Results: A high CYP4Z1 expression was observed in benign, primary and metastatic colon tissues compared to a weak or lack of expression in normal tissues. Importantly, there was a significant differential in CYP4Z1 expression where it was stronger in metastatic, primary and benign, respectively (p < 0.05). A significantly high rate of CYP4Z1 expression was found in high histological grades and late stages of the disease, where its expression was more evident in patients with metastasis in the lymph nodes (p < 0.05). Interestingly, CYP4Z1 expression was identified an independent prognostic predictor of poor overall survival of colon cancer patients (p = 0.003). Conclusion: CYP4Z1 was distinctly overexpressed in benign, primary and metastatic colon tissues compared to corresponding normal tissues. This differential in CYP4Z1 expression across different types of colon tissues strongly supports CYP4Z1 as potential biomarker and target for novel anticancer therapy development. [ABSTRACT FROM AUTHOR]

Purpose: Triple-negative breast cancer (TNBC) is characterized by high mortality rate, and its clinical management is difficult and complex. Therefore, there is a need for extensive efforts aimed at accelerating the discovery of novel therapies for TNBC. CYP4Z1 has been implicated in the development of breast cancer. The current study aimed at characterizing the expression of CYP4Z1 on TNBC. Materials and Methods: Using immunohistochemistry, CYP4Z1 expression was evaluated on 122 TNBC samples, four samples of breast cancers expressing ER, PR, and HER-2, and four samples of normal breast tissues. The association between the enzyme and various histopathological features and survival of patients were determined. Results: CYP4Z1 was strongly expressed in 83.3% of various histopathological subtypes of TNBC, when compared to negative expression in normal breast tissues. Interestingly, there were marked variations in CYP4Z1 expression with respect to histopathology subtype, histological grade, histological stage and tumor diameter. There was a high incidence of CYP4Z1 expression in patients with advanced grades, late stages and larger tumor sizes. Importantly, CYP4Z1 expression was correlated with the survival of TNBC patients, but it was an independent determinant of the poor prognosis of TNBC (p< 0.05). Conclusion: CYP4ZI may be a potential biomarker or target for evolving new CYP4Z1-targeted treatments. [ABSTRACT FROM AUTHOR]

Background: The development of colon cancer has been described as a multistep process of carcinogenesis. Understanding molecular and cellular changes underlying this process is required to determine potential biomarkers and therapeutic targets in colon cancers. Several molecular entities, including glypicans, are implicated in cancer development. Among these is glypican-6, which is overexpressed in a limited number of cancers. This study aims to characterise the glypican-6 expression in different types of colon cancer. Methods: Immunohistochemistry was used to characterise glypican-6 expression in a panel of archived formalin-fixed, paraffin-embedded colon tissue types. These types included 39 normal colon tissues, 10 colon tubular adenomas, 60 colon adenocarcinomas without metastasis and 60 colon adenocarcinomas with metastasis. Glypican-6 expression relation to demographic and clinicopathologic features was also examined. Results: Glypican-6 was strongly expressed in benign, primary and metastatic colon tumours. Normal tissue samples exhibited low to undetectable levels of glypican-6. A significantly high glypican-6 expression was displayed in colon cancers with lymph node metastasis, high depth of invasion, distant metastasis, high histological grades and late stages of the disease (P < 0.05). Importantly, a significant differential in glypican-6 expression was found between normal tissues and different types of colon cancer tissues. Moreover, the highest glypican-6 expression was more frequently found in metastatic tumours, followed by primary tumours and the least in benign tumours (P < 0.05). Conclusions: Selective expression of glypican-6 may establish a basis for potential use as a tissue biomarker or as a novel therapeutic target in treatment of colon cancer. [ABSTRACT FROM AUTHOR]