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High expression of sperm-associated antigen 5 correlates with poor survival in ovarian cancer.

ABSTRACT: OBJECTIVES:Sperm-associated antigen 5 (SPAG5), a spindle-binding protein, regulates the process of mitosis. The present study focused on the relationship between SPAG5 expression and the clinicopathological characteristics and prognosis of ovarian cancer. METHODS:First, we used the Gene Expression Omnibus (GEO) database to analyze SPAG5 expression in ovarian cancer and its clinical relevance. Subsequently, qPCR test was used to detect SPAG5 mRNA expression in 20 cases of ovarian cancer. The expression of SPAG5 protein in a tissue microarray containing 102 cases of ovarian cancer was detected by immunohistochemistry. Cox regression and Kaplan-Meier survival analyses were performed to identify the prognostic factors for the 102 ovarian cancer patients. RESULTS:In the GEO datasets, SPAG5 mRNA expression was significantly higher in ovarian cancer tissues than that in normal ovarian tissues (P < 0.001). qPCR and immunohistochemistry showed that SPAG5 expression in ovarian cancer tissues was significantly higher than that in paracancerous tissues (P = 0.002, P < 0.001). The high expression of SPAG5 in ovarian cancer was correlated with histological type (P = 0.009), lymph node metastasis (P = 0.001), distant metastasis (P = 0.001), TNM stage (P = 0.001), and prognosis (P = 0.001). The Kaplan-Meier curve indicated that rates of disease-free survival (DFS) and overall survival (OS) were even lower in patients with high SPAG5 expression. Multivariate analysis showed that SPAG5 expression (P = 0.001) and TNM staging (P = 0.002) were independent prognostic factors for the DFS of ovarian cancer. CONCLUSIONS:These results suggest that high SPAG5 expression was correlated with multiple clinicopathological features of ovarian cancer and can be used as an evaluation indicator for a poor ovarian cancer prognosis.

SUBMITTER: Zhang M

PROVIDER: S-EPMC7007403 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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High expression of sperm-associated antigen 5 correlates with poor survival in ovarian cancer.

Zhang Mei M Sha Ling L Hou Ning N Shi Chuanbing C Tan Lin L

Bioscience reports 20200201 2

<h4>Objectives</h4>Sperm-associated antigen 5 (SPAG5), a spindle-binding protein, regulates the process of mitosis. The present study focused on the relationship between SPAG5 expression and the clinicopathological characteristics and prognosis of ovarian cancer.<h4>Methods</h4>First, we used the Gene Expression Omnibus (GEO) database to analyze SPAG5 expression in ovarian cancer and its clinical relevance. Subsequently, qPCR test was used to detect SPAG5 mRNA expression in 20 cases of ovarian c ...[more]

PMID: 31985007

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Project description:The cause of death among the majority of epithelial ovarian cancer (EOC) patients involves passive dissemination of cancer cells within the peritoneal cavity and subsequent implantation of cancer spheroids into adjacent organs. Thus, it is important to identify the factors that mediate EOC metastasis and implantation, including clearance of the mesothelium. Sushi domain containing 2 (SUSD2) encodes a type I transmembrane protein containing several functional domains inherent to adhesion molecules. Immunohistochemical analysis determined the presence of SUSD2 in several subtypes of EOC, with the strongest staining observed in high-grade serous ovarian carcinomas (HGSOCs). A high-density, clinically annotated HGSOC tissue microarray was stained with an anti-SUSD2 antibody. Patients with tumors that had a low percentage of SUSD2 staining cells had a shorter median survival (31.7 months) compared with patients who had tumors with extensive SUSD2 staining (49.1 months; P-value=0.0083). To investigate the role of SUSD2 in HGSOCs, stable OVCAR3, OVSAHO and KURAMOCHI cell lines were established with knockdown (KD) or non-targeting (NT) of SUSD2. Boyden chamber and wound-healing assays demonstrated that OVCAR3, OVSAHO and KURAMOCHI SUSD2-KD cells migrated at significantly higher rates compared with their SUSD2 NT counterpart cell lines. Quantitative reverse transcription-PCR and western immunoblot analysis indicated an inverse relationship between SUSD2 and well-characterized mesenchymal proteins, including Twist-1, Zeb-1, N-cadherin, STEAP1, AHNAK, Snail-1, COL5A2 and Snail-3 in OVCAR3, OVSAHO and KURAMOCHI cell line models. In addition, OVCAR3 and KURAMOCHI SUSD2-KD spheroids displayed increased mesothelial clearance ability compared with cells that express endogenous levels of SUSD2. These data suggest that SUSD2 has a role in the inhibition of mesothelial clearance, which is required for metastasis. Altogether, our findings indicate that SUSD2 impedes migration, epithelial-to-mesenchymal transitional and mesothelial clearance of HGSOC cells, consistent with prolonged survival of patients with SUSD2-expressing tumors.

Project description:P53-induced gene 11 (PIG11) is an early transcription-related target of p53 that is involved in cell apoptosis and tumor development. However, its biological function in gastric cancer (GC) tissues and relationship with the prognosis of patients with GC have remained elusive. In the present retrospective study, 60 fresh and 790 paraffin-embedded samples of GC were obtained from the Affiliated Hospital of Nantong University (Nantong, China) with complete clinical data from all patients. Reverse transcription-quantitative PCR and tissue microarray-immunohistochemical analysis were used to determine the expression of PIG11 in the respective GC tissues. A receiver operating characteristic (ROC) curve was plotted to determine the diagnostic utility of PIG11 expression in GC. Furthermore, three online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine and Kaplan-Meier plotter, were used for bioinformatics analysis of PIG11. PIG11 expression in GC tissues was high, which was positively correlated with invasive depth (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.019), TNM staging (P<0.001) and carcinoembryonic antigen in serum (P<0.001), and negatively associated with the overall survival of patients with GC. The ROC curve analysis suggested that based on PIG11 expression, it was possible to distinguish GC tissues from adjacent normal tissues (P<0.0001) with a sensitivity and specificity of 81.67 and 76.67%, respectively. In addition, Cox logistic regression analysis demonstrated that high PIG11 expression is a novel biomarker for unfavorable prognosis of patients with GC. Furthermore, the results obtained from the GEPIA database indicated that PIG11 expression is correlated with TNF, carcinoembryonic antigen related cell adhesion molecule 5, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha, VEGFA and kinase insert domain receptor. Therefore, PIG11 expression may be associated with the malignancy of GC and may serve as a potential diagnostic and prognostic biomarker for GC.

Dataset Information

High expression of sperm-associated antigen 5 correlates with poor survival in ovarian cancer.

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High expression of sperm-associated antigen 5 correlates with poor survival in ovarian cancer.

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