Tumor Suppressive Role of the PRELP Gene in Ovarian Clear Cell Carcinoma

Dozen, Ai; Shozu, Kanto; Shinkai, Norio; Ikawa, Noriko; Aoyama, Rina; Machino, Hidenori; Asada, Ken; Yoshida, Hiroshi; Kato, Tomoyasu; Hamamoto, Ryuji; Kaneko, Syuzo; Komatsu, Masaaki

doi:10.3390/jpm12121999

Cited by 10 publications

(6 citation statements)

References 44 publications

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“…Proteins that have low or no expression in saliva or salivary glands were also excluded from the validation list. The final shortlisted hits, namely, peroxiredoxin‐4 (PRX‐IV), legumain, SIL1 nucleotide exchange factor (SIL1), and cellular repressor of E1A‐stimulated genes (CREG1), were chosen based on novelty, 27–41 and the absence of association with other oral diseases 42–47 …”

Section: Resultsmentioning

confidence: 99%

“…Proteins that have low or no expression in saliva or salivary glands were also excluded from the validation list. The final shortlisted hits, namely, peroxiredoxin-4 (PRX-IV), legumain, SIL1 nucleotide exchange factor (SIL1), and cellular repressor of E1A-stimulated genes (CREG1), were chosen based on novelty, [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] and the absence of association with other oral diseases. [42][43][44][45][46][47] 2.2 | Salivary PRX-IV and legumain are significantly upregulated in HFMD case samples from Singapore Dot blot validation assay was performed using saliva samples from HFMD-diagnosed patients and healthy volunteers in Singapore to assess the sensitivity and specificity of the respective biomarker(s).…”

Section: Nineteen Salivary Proteins Were Significantly Upregulated In...mentioning

confidence: 99%

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Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease

Tan,

Teo,

Ler

et al. 2023

Journal of Medical Virology

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The fight against hand, foot, and mouth disease (HFMD) remains an arduous challenge without existing point‐of‐care (POC) diagnostic platforms for accurate diagnosis and prompt case quarantine. Hence, the purpose of this salivary biomarker discovery study is to set the fundamentals for the realization of POC diagnostics for HFMD. Whole salivary proteome profiling was performed on the saliva obtained from children with HFMD and healthy children, using a reductive dimethylation chemical labeling method coupled with high‐resolution mass spectrometry‐based quantitative proteomics technology. We identified 19 upregulated (fold change = 1.5–5.8) and 51 downregulated proteins (fold change = 0.1–0.6) in the saliva samples of HFMD patients in comparison to that of healthy volunteers. Four upregulated protein candidates were selected for dot blot‐based validation assay, based on novelty as biomarkers and exclusions in oral diseases and cancers. Salivary legumain was validated in the Singapore (n = 43 healthy, 28 HFMD cases) and Taiwan (n = 60 healthy, 47 HFMD cases) cohorts with an area under the receiver operating characteristic curve of 0.7583 and 0.8028, respectively. This study demonstrates the feasibility of a broad‐spectrum HFMD POC diagnostic test based on legumain, a virus‐specific host systemic signature, in saliva.

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Section: Resultsmentioning

confidence: 99%

Section: Nineteen Salivary Proteins Were Significantly Upregulated In...mentioning

confidence: 99%

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease

Tan,

Teo,

Ler

et al. 2023

Journal of Medical Virology

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“…In addition, we demonstrated that Prelp was expressed in mouse retina and loss of Prelp contributed to retinoblastoma cell progression by reducing cell-cell adhesion and facilitated EMT (Hopkins et al, 2022). We further investigated the roles in other tumors and identified that PRELP showed a tumor suppressive role by regulated PI3K-AKT signalling pathway in highgrade ovarian cancer (Dozen et al, 2022).…”

Section: Methodsmentioning

confidence: 92%

Epithelial Barrier Dysfunction in Disease

Pardo-Pastor,

López Posadas,

Ortiz Zapater

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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“…There exists increasing evidence about the clinical relevance of PRELP as a tumor suppressor in solid tumors and its use as a prognostic marker [ 30 , 38 , 84 ]. In this study, the PRELP expression status was significantly associated with the patients’ prognosis.…”

Section: Discussionmentioning

confidence: 99%

Correlation of the tumor escape phenotype with loss of PRELP expression in melanoma

Schäfer,

Subbarayan,

Massa

et al. 2023

J Transl Med

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Background Despite immunotherapies having revolutionized the treatment of advanced cutaneous melanoma, effective and durable responses were only reported in a few patients. A better understanding of the interaction of melanoma cells with the microenvironment, including extracellular matrix (ECM) components, might provide novel therapeutic options. Although the ECM has been linked to several hallmarks of cancer, little information is available regarding the expression and function of the ECM protein purine-arginine-rich and leucine-rich protein (PRELP) in cancer, including melanoma. Methods The structural integrity, expression and function of PRELP, its correlation with the expression of immune modulatory molecules, immune cell infiltration and clinical parameters were determined using standard methods and/or bioinformatics. Results Bioinformatics analysis revealed a heterogeneous, but statistically significant reduced PRELP expression in available datasets of skin cutaneous melanoma when compared to adjacent normal tissues, which was associated with reduced patients’ survival, low expression levels of components of the MHC class I antigen processing machinery (APM) and interferon (IFN)-γ signal transduction pathway, but increased expression of the transforming growth factor (TGF)-β isoform 1 (TFGB1) and TGF-β receptor 1 (TGFBR1). In addition, a high frequency of intra-tumoral T cells directly correlated with the expression of MHC class I and PRELP as well as the T cell attractant CCL5 in melanoma lesions. Marginal to low PRELP expression levels were found in the 47/49 human melanoma cell lines analysis. Transfection of PRELP into melanoma cell lines restored MHC class I surface expression due to transcriptional upregulation of major MHC class I APM and IFN-γ pathway components. In addition, PRELP overexpression is accompanied by high CCL5 secretion levels in cell supernatant, an impaired TGF-β signaling as well as a reduced cell proliferation, migration and invasion of melanoma cells. Conclusions Our findings suggest that PRELP induces the expression of MHC class I and CCL5 in melanoma, which might be involved in an enhanced T cell recruitment and immunogenicity associated with an improved patients’ outcome. Therefore, PRELP might serve as a marker for predicting disease progression and its recovery could revert the tumorigenic phenotype, which represents a novel therapeutic option for melanoma.

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Tumor Suppressive Role of the PRELP Gene in Ovarian Clear Cell Carcinoma

Cited by 10 publications

References 44 publications

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease

Epithelial Barrier Dysfunction in Disease

Correlation of the tumor escape phenotype with loss of PRELP expression in melanoma

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