Identification of CpG Sites of SERPINA5 Promoter with Opposite Methylation Patterns in Benign and Malignant Prostate Cells

Hagelgans, Albert; Jandeck, Carsten; Friedemann, Markus; Donchin, Anastasia; Richter, Susan; Menschikowski, Mario

doi:10.21873/anticanres.12118

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…SERPINA5 is an important component of the SERPIN family known as a putative tumour suppressor gene [77]. It inhibits the activation of PSA and kallikrein, and it boosts sperm motility and fertilization in many studies [78]. The decreased expression of SERPINA5 seen in our discovery cohort and elevated PSA levels in newly diagnosed PCa patients compared with healthy individuals fits well with current research.…”

Section: Discussionsupporting

confidence: 87%

A Novel Blood Proteomic Signature for Prostate Cancer

Muazzam

Spick

Cexus

et al. 2023

Cancers

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Prostate cancer is the most common malignant tumour in men. Improved testing for diagnosis, risk prediction, and response to treatment would improve care. Here, we identified a proteomic signature of prostate cancer in peripheral blood using data-independent acquisition mass spectrometry combined with machine learning. A highly predictive signature was derived, which was associated with relevant pathways, including the coagulation, complement, and clotting cascades, as well as plasma lipoprotein particle remodeling. We further validated the identified biomarkers against a second cohort, identifying a panel of five key markers (GP5, SERPINA5, ECM1, IGHG1, and THBS1) which retained most of the diagnostic power of the overall dataset, achieving an AUC of 0.91. Taken together, this study provides a proteomic signature complementary to PSA for the diagnosis of patients with localised prostate cancer, with the further potential for assessing risk of future development of prostate cancer. Data are available via ProteomeXchange with identifier PXD025484.

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Section: Discussionsupporting

confidence: 87%

A Novel Blood Proteomic Signature for Prostate Cancer

Muazzam

Spick

Cexus

et al. 2023

Cancers

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“…In this study, we found that SERPINA5 expression was significantly correlated with OS and RFS in LGG patients, and SERPINA5 high expression indicated patients with worse survival. More recently, researchers have found that the high methylation degree of CpG sites significantly correlated with lower SERPINA5 expression levels and two distinct CpG sites of the SERPINA5 promoter were hypermethylated in normal epithelial prostate cells, benign hyperplasic cells and low-invasive malignant LNCaP cells, whereas essentially unmethylated in aggressive DU-145 and PC-3 cell line (Hagelgans et al, 2017). In addition, SERPINA5 has been identified to be more highly methylated in HR-, basal-like, or p53 mutant breast cancer than HR+, luminal A, or p53 wild-type breast cancers, and gene signature composed of SERPINA5 and 3 other genes can predict the prognosis of patients with stage I LUAD (Conway et al, 2014;Luo, Wang & Zhang, 2018).…”

Section: Discussionmentioning

confidence: 99%

Identification of gene expression and DNA methylation of SERPINA5 and TIMP1 as novel prognostic markers in lower-grade gliomas

Zeng

Yi²,

Wen

et al. 2020

PeerJ

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Background Lower-grade gliomas (LGGs) is characteristic with great difference in prognosis. Due to limited prognostic biomarkers, it is urgent to identify more molecular markers to provide a more objective and accurate tumor classification system for LGGs. Methods In the current study, we performed an integrated analysis of gene expression data and genome-wide methylation data to determine novel prognostic genes and methylation sites in LGGs. Results To determine genes that differentially expressed between 44 short-term survivors (<2 years) and 48 long-term survivors (≥2 years), we searched LGGs TCGA RNA-seq dataset and identified 106 differentially expressed genes. SERPINA5 and TIMP1 were selected for further study. Kaplan–Meier plots showed that SERPINA5 and TIMP1 expression were significantly correlated with overall survival (OS) and relapse-free survival (RFS) in TCGA LGGs patients. We next validated the correlation between the candidate genes expression and clinical outcome in CGGA LGGs patients. Multivariate analysis showed that TIMP1 mRNA expression had a significant prognostic value independent of other variables (HR = 4.825, 95% CI = 1.370–17.000, P = 0.014). Then, differential methylation sites were identified from differentially candidate gene expression groups, and all four methylation sites were significantly negatively correlated with gene expression (spearman r < − 0.5, P < 0.0001). Moreover, hyper-methylation of four methylation sites indicated better OS (P < 0.05), and three of them also shown statistical significantly association with better RFS, except for SERPINA5 cg15509705 (P = 0.0762). Conclusion Taken together, these findings indicated that the gene expression and methylation of SERPINA5 and TIMP1 may serve as prognostic predictors in LGGs and may help to precise the current histology-based tumors classification system and to provide better stratification for future clinical trials.

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Therapeutic exosomes loaded with SERPINA5 attenuated endometrial cancer cell migration via the integrin β1/FAK signaling pathway

Song

Tan

et al. 2022

Cell Oncol.

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Identification of CpG Sites of SERPINA5 Promoter with Opposite Methylation Patterns in Benign and Malignant Prostate Cells

Abstract: Novel methylation patterns of two distinct CpG sites of the SERPINA5 promoter may be useful for differentiating benign from malignant prostate disease.

Cited by 4 publications

References 28 publications

A Novel Blood Proteomic Signature for Prostate Cancer

A Novel Blood Proteomic Signature for Prostate Cancer

Identification of gene expression and DNA methylation of SERPINA5 and TIMP1 as novel prognostic markers in lower-grade gliomas

Therapeutic exosomes loaded with SERPINA5 attenuated endometrial cancer cell migration via the integrin β1/FAK signaling pathway

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