Overexpression of trophoblast cell surface antigen 2 as an independent marker for a poor prognosis and as a potential therapeutic target in epithelial ovarian carcinoma

Xu, Ning; Zhang, Zhihong; Zhu, Jin; Xu, Lei; Li, Yuhua; Duan, Lei; Yuan, Man; Li, Hongxia

doi:10.1111/iep.12174

Cited by 25 publications

(15 citation statements)

References 35 publications

(56 reference statements)

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“…Some of the proteins in the 11-protein panel, aside from MUCIN-16 and WFDC2 (HE4), have previously been associated to ovarian cancer. TACSTD2 (tumor-associated calcium signal transducer 2) expression has been associated with decreased survival of ovarian cancer and proposed as a prognostic factor 24 , and a biomarker for targeted therapy 25 . SPINT1 (matriptase, HAI-2) is a type II transmembrane serine protease expressed on epithelial ovarian tumor cells.…”

Section: Discussionmentioning

confidence: 99%

High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer

et al. 2019

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Ovarian cancer is usually detected at a late stage and the overall 5-year survival is only 30–40%. Additional means for early detection and improved diagnosis are acutely needed. To search for novel biomarkers, we compared circulating plasma levels of 593 proteins in three cohorts of patients with ovarian cancer and benign tumors, using the proximity extension assay (PEA). A combinatorial strategy was developed for identification of different multivariate biomarker signatures. A final model consisting of 11 biomarkers plus age was developed into a multiplex PEA test reporting in absolute concentrations. The final model was evaluated in a fourth independent cohort and has an AUC = 0.94, PPV = 0.92, sensitivity = 0.85 and specificity = 0.93 for detection of ovarian cancer stages I–IV. The novel plasma protein signature could be used to improve the diagnosis of women with adnexal ovarian mass or in screening to identify women that should be referred to specialized examination.

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Section: Discussionmentioning

confidence: 99%

High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer

et al. 2019

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“…The knockdown of Trop2 can suppress the proliferation and metastasis of lung adenocarcinoma H460 cells . Thus, Trop2 gene was a valuable therapeutic target for various cancers . In this study, it is first discovered that the Trop2 protein was highly expressed in EC KLE and Ishikawa cell lines compared with that in endometrial epithelial cells.…”

Section: Discussionmentioning

confidence: 93%

Knockdown of Trop2 inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/β‐catenin pathway

Sun

Xing

Zhang

et al. 2020

Cell Biochemistry & Function

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Endometrial cancer (EC) is the most common gynaecologic malignancy in western countries and has been reported to account for about 7% of female malignant tumours and 20% to 30% of female genital system malignant tumours. Accumulating evidence showed the expression of human trophoblast cell surface antigen 2 (Trop2) was abnormal in many cancers; however, the expression and role of Trop2 in EC are not clear. The Trop-2 protein expression was detected by western blot in EC cells.Cell proliferation, apoptosis, and migration were measured by CCK-8, flow cytometry, and Transwell assay, respectively. The epithelial mesenchymal transition (EMT) and AKT/β-catenin signalling pathway-related proteins in EC cell lines were detected by western blot assay following Trop2 gene silencing. The present study revealed that the Trop2 protein was highly expressed in EC cell lines compared with human endometrial epithelial cells. The Trop2 mRNA and protein were obviously decreased following transfection with Trop2-siRNA sequence in KLE and Ishikawa cells. Meanwhile, Trop2 gene silencing in KLE and Ishikawa cells strongly inhibited cell proliferation and migration and increased cell apoptosis. Investigation into the molecular mechanism indicated that the Trop2 gene silencing suppressed EMT and AKT/β-catenin signalling pathway activation.Significance of the study: These findings suggested that Trop2 silencing inhibited EC cell proliferation and migration and promoted cell apoptosis. The mechanism might be related to the inhibition of the AKT/β-catenin signalling pathway in EC cells. Therefore, Trop2 may be a potential therapeutic target for the treatment of EC. K E Y W O R D S AKT/β-catenin pathway, apoptosis, endometrial cancer, epithelial-to-mesenchymal transition, proliferation, Trop2 1 | INTRODUCTION Endometrial cancer (EC) is the second most common gynaecologic malignancy in China and has increasingly high incidence in younger women. 1,2 Despite enormous efforts in diagnosis and clinical treatment, the 5-year survival rate of EC is still less than 69%. 3 Risk factors for the development of EC are complex, including family history, hormonal imbalance, obesity, and hyperinsulinemia. A previous study has shown that the poor prognosis of EC patients who were diagnosed with International Federation of Gynecology and

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“…A total of 4,852 patients were enrolled (sample size: maximum: 702, minimum: 47, and mean: 167), and 16 carcinoma types were analyzed, including lung cancer (6, different subtypes), colorectal cancer (4), bladder cancer (2), breast cancer (2), gallbladder cancer (2), gastric cancer (2), ovarian carcinoma (2), cervical cancer (1), endometrioid endometrial carcinoma (1), extranodal natural killer (NK)/T cell lymphoma/nasal type (1), hilar cholangiocarcinoma (1), laryngeal squamous cell carcinoma (1), nasopharyngeal carcinoma (1), pancreatic cancer (1), pituitary adenomas (1), and squamous cell carcinoma of oral cavity (1). A total of 47 HRs/RRs were extracted from 29 studies, including 26 for OS, 6 for DFS, 15 , 34 , 35 , 41 , 44 , 56 5 for PFS, 13 , 34 , 35 , 39 , 57 4 for DR, 38 , 49 , 57 , 58 3 for CSS, 55 and 1 for DFS/PFS. 59 Study quality was evaluated by using the Newcastle–Ottawa Scale (NOS), and the quality scores ranged from 6 to 9, suggesting high methodological quality.…”

Section: Resultsmentioning

confidence: 99%

Prognostic role and clinical significance of trophoblast cell surface antigen 2 in various carcinomas

Zhao

Liu

et al. 2017

CMAR

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IntroductionTrophoblast cell surface antigen 2 (TROP2) has been linked to disease prognosis in various human cancers and plays a critical role in tumor development, progression, and metastasis. A number of relevant studies have been published on this topic. A meta-analysis of the latest literature to evaluate the value of TROP2 as a predictive prognosticator of cancer was performed.MethodsSeveral online databases were searched, and relevant articles were retrieved. Overall and subcategory meta-analyses were performed, and results were collated.ResultsTwenty-seven articles, including 29 studies, were included, involving 4,852 cancer patients, and results showed that the above-baseline expression of TROP2 was significantly associated with poorer overall survival (OS) (pooled hazard ratio [HR]: 1.84, 95% confidence interval [CI]: 1.45–2.35), disease-free survival (DFS) (pooled HR: 2.77, 95% CI: 1.73–4.42), and progression-free survival (PFS) (pooled HR: 1.71, 95% CI: 1.25–2.35). The following clinical characteristics were also significantly linked with TROP2 overexpression: moderate/poor differentiation (pooled HR: 3.03, 95% CI: 1.99–4.63), distant metastasis (pooled HR: 2.46, 95% CI: 1.05–5.75), lymph node metastasis (pooled HR: 2.47, 95%: CI 1.72–3.56), and advanced TNM stage (pooled HR: 2.02, 95% CI: 1.38–2.95).ConclusionTROP2 overexpression was predictive of poor prognosis in human cancers and may be an independent prognostic predictive biomarker. Further studies should be performed to confirm the significance of TROP2 in clinical practice.

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Overexpression of trophoblast cell surface antigen 2 as an independent marker for a poor prognosis and as a potential therapeutic target in epithelial ovarian carcinoma

Cited by 25 publications

References 35 publications

High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer

High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer

Knockdown of Trop2 inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/β‐catenin pathway

Prognostic role and clinical significance of trophoblast cell surface antigen 2 in various carcinomas

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