scholarly journals Serum Levels of S100A11 and MMP-9 in Patients with Epithelial Ovarian Cancer and Their Clinical Significance

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Wenjing Li ◽  
Zhumei Cui ◽  
Yan Kong ◽  
Xiangyu Liu ◽  
Xiangyu Wang

Objective. To investigate the serum levels of calgizzarin (S100A11) and matrix metalloproteinase-9 (MMP9) in patients with epithelial ovarian cancer (EOC) and determine their clinical significance. Methods. Serum levels of S100A11 and MMP9 were detected in patients with EOC, patients with benign ovarian tumor, and healthy women. The correlation between the two markers and clinicopathological characteristics of ovarian cancer was analysed. Results. The serum levels of S100A11 and MMP-9 in patients with EOC were higher than those in patients with benign ovarian tumor and in healthy women, and the expression levels of S100A11 and MMP-9 were positively correlated. S100A11 and MMP-9 were correlated with tumor staging, postoperative residual foci, ascites volume, serum CA125 level, chemotherapy response, and lymph node metastasis, while S100A11 and MMP-9 were not associated with the bilevel classification, histological type, age, and degree of differentiation. Conclusion. S100A11 and MMP-9 were both highly expressed in the serum of patients with EOC and were associated with cancer development, invasion, and metastasis. Therefore, they can be used as an important reference maker in the diagnosis and treatment of ovarian cancer.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meysam Yousefi ◽  
Sara Rajaie ◽  
Vahideh Keyvani ◽  
Somayeh Bolandi ◽  
Malihe Hasanzadeh ◽  
...  

AbstractCirculating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).



2020 ◽  
Vol Volume 12 ◽  
pp. 637-649 ◽  
Author(s):  
Chen-Yu Huang ◽  
Wen-Hsun Chang ◽  
Hsin-Yi Huang ◽  
Chao-Yu Guo ◽  
Yiing-Jenq Chou ◽  
...  


2019 ◽  
Author(s):  
Xingchen Zhou ◽  
Xiaoli Wu ◽  
Xiaoduan Li ◽  
Yi Zhang ◽  
Xipeng Wang

Abstract Purpose: To study the role of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway in patients with epithelial ovarian cancer (EOC). Methods: A total of 10 EOC specimens and 10 benign ovarian tumor were obtained from surgery and the pathological type. We used the methods of immunofluorescence confocal microscopy, western blot, MTT assay, apoptosis detection and co-culture to verify the aim of the research. Results: In the present study, it was validated that the number of PD-L1+ tumor-associated macrophages (TAMs) per field was significantly increased in EOC tissues compared with benign ovarian tumor tissues. Furthermore, it was demonstrated that PD-L1 was expressed on the membrane of TAM-derived exosomes, which may inhibit the proliferation and induce the apoptosis of T cells by activating the caspase 3 signaling pathway. The analysis of the supernatant of T cells co-cultured with TAM drived exosome revealed that the levels of pro-inflammatory cytokines and tumor necrosis factor α decreased compared with those T cells co-cultured with monocyte drived exosome. However, the expression of the immuno-suppressive cytokine, interleukin 10 and markers of T cell exhaustion (the inhibitory molecule lymphocyte activated gene-3, T-cell immunoglobulin and mucin domain-containing protein-3 and PD-1) increased. Conclusions: The present study demonstrated that the M2-derived exosomes regulate immune suppression in the EOC microenvironment. The findings of the present study provide a theoretical basis for future target therapy on exosomes from immune cells to treat EOC.



2017 ◽  
Vol 27 (7) ◽  
pp. 1343-1349 ◽  
Author(s):  
Zhen Yan ◽  
Xiaoyu Tian ◽  
Ruifang Wang ◽  
Xiaolin Cheng ◽  
Jianqiang Mi ◽  
...  

ObjectiveThis study aimed to evaluate the prognosis significance of zinc-finger E-box binding homeobox 2 (ZEB2) and transforming growth factor β1 (TGF-β1) as well as other clinical characteristics in epithelial ovarian cancer (EOC).MethodsThis retrospective study examined the expressions of ZEB2 and TGF-β1 in 64 EOC specimens, 36 benign ovarian tumor specimens, and 28 normal ovarian specimens by immunohistochemistry. The correlation of the expressions of ZEB2 and TGF-β1 was analyzed by the Spearman rank correlation analysis. The Kaplan-Meier method was used to construct crude survival curves, and the prognostic roles of ZEB2 and TGF-β1 as well as clinical characteristics were evaluated by Cox proportional hazards regression analysis.ResultsThe positive expression rates of ZEB2 and TGF-β1 were increased in EOC specimens compared with benign ovarian tumor and normal ovary specimens (P < 0.05), and ZEB2 expression was positively correlated with TGF-β1 expression (r = 0.538, P = 0.000). In addition, the overall survival rate of EOC patients was associated with the expressions of ZEB2 and TGF-β1, age, differentiated grade, International Federation of Gynecology and Obstetrics (FIGO) stage, preoperative serum CA125 level, postoperative start time of chemotherapy, and treatment course (all P < 0.05). Multivariate Cox regression demonstrated that FIGO stage (P = 0.033), TGF-β1 expression (P = 0.043), postoperative start time of chemotherapy (P = 0.009), and treatment course (P = 0.000) were prognostic factors for EOC.ConclusionsZEB2 and TGF-β1 may promote EOC progression, and FIGO stage, TGF-β1 expression, postoperative start time of chemotherapy, and treatment course may be associated with the prognosis of EOC.



2016 ◽  
Vol 27 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Tao Zhu ◽  
Wen Gao ◽  
Xi Chen ◽  
Ying Zhang ◽  
Meijuan Wu ◽  
...  

ObjectiveEarly diagnosis of epithelial ovarian cancer is critical for patient survival. The objective of this pilot study is to identify a circulating micro (mi)RNA as a potential biomarker for epithelial ovarian cancer.MethodsA total of 135 epithelial ovarian cancer patients and 54 benign ovarian tumor patients were recruited for this study. Using customized TaqMan low density miRNA arrays, we first screened expression levels of 48 miRNAs in sera from 18 epithelial ovarian cancer patients and 16 benign ovarian tumor patients. The most significantly and differentially expressed miRNA was then further examined in all serum samples using real-time polymerase chain reaction. Its expression was further analyzed in relationship with clinicopathological factors and patient survival.ResultsArray screening data showed that expression levels of serum miRNA-20a, miRNA-125b, miRNA-126, miRNA-355, and let-7c were significantly different between malignant and benign ovarian tumor patients. Subsequent real-time polymerase chain reaction results showed that serum miRNA-125b levels were significantly higher in epithelial ovarian cancer patients compared to benign controls. Moreover, serum miRNA-125b levels were significantly higher in ovarian cancer patients in early stages I and II, and in patients having no residual tumor following surgery, but were not associated with differentiation and histological types of ovarian cancer. Notably, the higher level of miR-125b was significantly positively correlated with progression-free survival (P= 0.035) and marginally, with overall survival (P =0.069).ConclusionsmiRNA-125b plays an important role in the pathogenesis and progression of epithelial ovarian cancer. Circulating miRNA-125b has the potential to become a novel biomarker for early diagnosis and prognosis prediction of epithelial ovarian cancer.



2018 ◽  
Vol 2 (3) ◽  
Author(s):  
MoonSun Jung ◽  
Amanda J Russell ◽  
Catherine Kennedy ◽  
Andrew J Gifford ◽  
Kylie-Ann Mallitt ◽  
...  

Abstract Background The Myc oncogene family has been implicated in many human malignancies and is often associated with particularly aggressive disease, suggesting Myc as an attractive prognostic marker and therapeutic target. However, for epithelial ovarian cancer (EOC), there is little consensus on the incidence and clinical relevance of Myc aberrations. Here we comprehensively investigated alterations in gene copy number, expression, and activity for Myc and evaluated their clinical significance in EOC. Methods To address inconsistencies in the literature regarding the definition of copy number variations, we developed a novel approach using quantitative polymerase chain reaction (qPCR) coupled with a statistical algorithm to estimate objective thresholds for detecting Myc gain/amplification in large cohorts of serous (n = 150) and endometrioid (n = 80) EOC. MYC, MYCN, and MYCL1 mRNA expression and Myc activity score for each case were examined by qPCR. Kaplan–Meier and Cox-regression analyses were conducted to assess clinical significance of Myc aberrations. Results Using a large panel of cancer cell lines (n = 34), we validated the statistical algorithm for determining clear thresholds for Myc gain/amplification. MYC was the most predominantly amplified of the Myc oncogene family members, and high MYC mRNA expression levels were associated with amplification in EOC. However, there was no association between prognosis and increased copy number or gene expression of MYC/MYCN/MYCL1 or with a pan-Myc transcriptional activity score, in EOC, although MYC amplification was associated with late stage and high grade in endometrioid EOC. Conclusion A systematic and comprehensive analysis of Myc genes, transcripts, and activity levels using qPCR revealed that although such aberrations commonly occur in EOC, overall they have limited impact on outcome, suggesting that the biological relevance of Myc oncogene family members is limited to certain subsets of this disease.





2020 ◽  
Author(s):  
Liancheng Zhu ◽  
Mingzi Tan ◽  
Haoya Xu ◽  
Bei Lin

Abstract Background.Human Epididymis Protein 4 (HE4) is a novel serum biomarker for diagnosis of epithelial ovarian cancer (EOC) with high specificity and sensitivity compared with CA125, and the increasing researches have been carried out on its roles in promoting carcinogenesis and chemoresistance in EOC in recent years, however, its underlying molecular mechanisms remain poorly understood. The aim of this study was to elucidate the molecular mechanisms of HE4 stimulation and to identify the key genes and pathways mediating carcinogenesis in EOC using microarray and bioinformatics analysis.Methods. We established a stable HE4-silence ES-2 ovarian cancer cell line labeled as “S”, and its active HE4 protein stimulated cells labeled as “S4”. Human whole genome microarray analysis was used to identify deferentially expressed genes (DEGs) from triplicate samples of S4 and S cells. “clusterProfiler” package in R, DAVID, Metascape, and Gene Set Enrichment Analysis (GSEA) were used to perform gene ontology (GO) and pathway enrichment analysis, and cBioPortal for WFDC2 coexpression analysis. GEO dataset (GSE51088) and quantitative real-time polymerase chain reaction (qRT-PCR) was applied for validation. The protein–protein interaction (PPI) network and modular analyses were performed using Metascape and Cytoscape. Results.In total, 713 DEGs were found (164 up regulated and 549 down regulated) and further analyzed by GO, pathway enrichment and PPI analyses. We found that MAPK pathway accounted for a significant portion of the enriched terms. WFDC2 coexpression analysis revealed ten WFDC2 coexpressed genes (TMEM220A, SEC23A, FRMD6, PMP22, APBB2, DNAJB4, ERLIN1, ZEB1, RAB6B, and PLEKHF1) that were also dramatically changed in S4 cells and validated by dataset GSE51088. Kaplan–Meier survival statistics revealed clinical significance for all of the 10 target genes. Finally, PPI was constructed, sixteen hub genes and eight molecular complex detections (MCODEs) were identified, the seeds of five most significant MCODEs were subjected to GO and KEGG enrichment analysis and their clinical significance was evaluated.Conclusions.By applying microarray and bioinformatics analyses, we identified DEGs and determined a comprehensive gene network of active HE4 stimulation in EOC cells. We offered several possible mechanisms and identified therapeutic and prognostic targets of HE4 in EOC.



2021 ◽  
pp. 67-78
Author(s):  
Varvara Nikolaevna Zhurman ◽  
Natalia Gennadevna Plekhova ◽  
Ekaterina Valeryevna Eliseeva

The article is a review of the literature, which analyzes the data on the role of cells of the immune system, cytokines and other biologically active substances secreted by them in the interstitial space of an ovarian tumor. The emphasis is made on the mechanism of realization by immune cells of the stimulating and suppressing action on the development of the tumor. Considerable attention is paid to the prognostic role of immune cells in the development of epithelial ovarian cancer.



Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1309 ◽  
Author(s):  
Se Ik Kim ◽  
Nayeon Kang ◽  
Sangseob Leem ◽  
Jinho Yang ◽  
HyunA Jo ◽  
...  

We aimed to develop a diagnostic model identifying ovarian cancer (OC) from benign ovarian tumors using metagenomic data from serum microbe-derived extracellular vesicles (EVs). We obtained serum samples from 166 patients with pathologically confirmed OC and 76 patients with benign ovarian tumors. For model construction and validation, samples were randomly divided into training and test sets in the ratio 2:1. Isolation of microbial EVs from serum samples of the patients and 16S rDNA amplicon sequencing were carried out. Metagenomic and clinicopathologic data-based OC diagnostic models were constructed in the training set and then validated in the test set. There were significant differences in the metagenomic profiles between the OC and benign ovarian tumor groups; specifically, genus Acinetobacter was significantly more abundant in the OC group. More importantly, Acinetobacter was the only common genus identified by seven different statistical analysis methods. Among the various metagenomic and clinicopathologic data-based OC diagnostic models, the model consisting of age, serum CA-125 levels, and relative abundance of Acinetobacter showed the best diagnostic performance with the area under the receiver operating characteristic curve of 0.898 and 0.846 in the training and test sets, respectively. Thus, our findings establish a metagenomic analysis of serum microbe-derived EVs as a potential tool for the diagnosis of OC.



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