Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions

Bernreuther, Christian; Daghigh, Ferdous; Möller, Katharina; Hube‐Magg, Claudia; Lennartz, Maximilian; Lutz, Florian; Rico, Sebastian Dwertmann; Fraune, Christoph; Dum, David; Luebke, Andreas M.; Eichenauer, Till; Möller‐Koop, Christina; Schlomm, Thorsten; Wittmer, Corinna; Huland, Hartwig; Heinzer, Hans; Graefen, Markus; Haese, Alexander; Burandt, Eike; Clauditz, Till S.; Höflmayer, Doris; Izbicki, Jakob R.; Simon, Ronald; Sauter, Guido; Minner, Sarah; Steurer, Stefan; Meiners, Jan

doi:10.1007/s12253-020-00861-9

Cited by 9 publications

(8 citation statements)

References 67 publications

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“…11 While there is evidence for an increase in sFRP4 expression in various cancers, some studies have shown a decrease. [39][40][41] In our study, sFRP4 levels did not differ in CRC patients compared to healthy individuals, this may be due to the limited number of patients. It is important to note the discrepancies in findings and further research is required to fully understand the role of sFRP4 in cancer.…”

Section: Discussioncontrasting

confidence: 54%

EXPLORING THE ROLE OF sFRP-4, TFF-3, NF-кB AND ROMO1 LEVELS IN COLORECTAL CANCER: IMPLICATIONS FOR PATHOPHYSIOLOGY AND DISEASE PROGRESSION

DURMUŞ,

PAPİLA KUNDAKTEPE,

GELİŞGEN

et al. 2024

Acta Medica Nicomedia

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Objective: Colorectal cancer (CRC) is a significant global health concern with high morbidity and mortality rates. Early detection and accurate diagnostic tools are critical for improving patient outcomes. Our aim in this study was to investigate the diagnostic significance of specific biomarkers - secreted frizzled associated protein-4 (sFRP-4), trefoil factor-3 (TFF-3), nuclear factor-kappa-B (NF-κB), and reactive oxygen species modulator-1 (Romo1) - in patients with CRC. Methods: This study analyzed plasma levels of sFRP-4, TFF-3, NF-κB and Romo1 in a cohort of patients with CRC (n=50) and age- and gender-matched control group (n=40), utilizing ELISA. The diagnostic performance of these biomarkers was assessed through Receiver Operating Characteristic (ROC) analysis. Results: Our research revealed a significant increase in the levels of NF-κB, TFF-3 and Romo1 in patients with a diagnosis of CRC. Furthermore, these parameters were found to maintain elevated levels in patients with tumours larger than 4 cm as opposed to those with smaller tumours. Patients with metastases also had elevated levels of the three parameters compared with patients without metastases. The ROC analysis revealed that NF-κB showed the most promise as a parameter for distinguishing patients from control subjects, whereas TFF-3 displayed the most potential in identifying tumour size and the presence of metastasis. Conclusions: This research contributes valuable insights into the development of non-invasive diagnostic approaches for CRC. The potential of NF-κB, TFF-3 and Romo1 as biomarkers offers a novel avenue for early detection and improved management of CRC, ultimately contributing to better patient outcomes. Further validation and prospective studies are warranted to establish the clinical utility of these biomarkers in CRC diagnosis and screening programs.

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Section: Discussioncontrasting

confidence: 54%

EXPLORING THE ROLE OF sFRP-4, TFF-3, NF-кB AND ROMO1 LEVELS IN COLORECTAL CANCER: IMPLICATIONS FOR PATHOPHYSIOLOGY AND DISEASE PROGRESSION

DURMUŞ,

PAPİLA KUNDAKTEPE,

GELİŞGEN

et al. 2024

Acta Medica Nicomedia

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“…The SFRP4 protein is a suggested tumor suppressor thought to inhibit Wnt-signaling by hindering the extracellular Wnt-ligand to attach to the receptor 5 . However, we and others have identi ed increased SFRP4 gene expression with increasing prostate cancer aggressiveness [6][7][8][9] , which also have been found for several other cancers 10 . In the context of personalized medicine, SFRP4 gene expression has the potential to improve diagnosis and prognosis accuracy.…”

Section: Introductionsupporting

confidence: 61%

Spatial transcriptomics reveals strong association between SFRP4 and extracellular matrix remodeling in prostate cancer

Andersen,

Krossa,

Midtbust

et al. 2023

Preprint

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Increased gene expression levels of secreted frizzled-related protein 4 (SFRP4) is a biomarker in aggressive prostate cancer. Prostate tumor heterogeneity is a major obstacle when studying the biological mechanisms of molecular markers. To understand how SFRP4 relates to prostate cancer we performed comprehensive spatial and multiomics analysis of the same prostate cancer tissue samples. The experimental workflow included spatial transcriptomics, bulk transcriptomics, proteomics, DNA methylomics and tissue staining. SFRP4 mRNA was predominantly located in cancer stroma, produced by fibroblasts and smooth muscle cells, and co-expressed with extracellular matrix components. We also confirmed that higher SFRP4gene expression is associated with cancer aggressiveness. Gene expression of SFRP4was affected by gene promotor methylation. Surprisingly, the high mRNA levels did not reflect SFRP4 protein levels, which was much lower. This study contributes previously unknown insights of SFRP4 mRNA in the prostate tumor environment that potentially can improve diagnosis and treatment. Teaser: Combining a comprehensive set of different methods on the same samples reveals new understanding of SFRP4 in prostate cancer

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“…SFRP4 overexpression in both androgen-dependent and androgen-independent cell lines resulted in a morphologic change to a more epithelioid cell type with increased localization of b-catenin and cadherins (Ecadherin in LNCaP, N-cadherin in PC3) to the cell membrane (38). Previous studies showed that SFRP4 overexpression was linked to advanced tumor stage, high classical/quantitative Gleason grade (p < 0.0001 each), lymph node metastasis (p = 0.0002), and a positive surgical margin (p = 0.0017), and SFRP4 expression was an independent predictor of recurrence after prostatectomy (HR = 1.35; p = 0.009) (22,37). In addition, SPP1 is a cardinal mediator of tumor-associated inflammation and facilitates metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we firstly developed and confirmed that EMTGPI could predict BCR probability and drug resistance effectively for PCa patients undergoing radical prostatectomy or radiotherapy. SFRP4 controls WNT signaling and is thought to play a role for tumor aggressiveness ( 37 ). SFRP4 overexpression in both androgen-dependent and androgen-independent cell lines resulted in a morphologic change to a more epithelioid cell type with increased localization of β-catenin and cadherins (E-cadherin in LNCaP, N-cadherin in PC3) to the cell membrane ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer

et al. 2022

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BackgroundWe aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa).MethodsWe used Lasso and Cox regression analysis to establish the EMTGPI. All analyses were conducted with R version 3.6.3 and its suitable packages.ResultsWe established the EMTGPI based on SFRP4 and SPP1. Patients in high-risk group had 2.23 times of BCR risk than those in low-risk group (p = 0.003), as well as 2.36 times of metastasis risk (p = 0.053). In external validation, we detected similar diagnostic efficacy and prognostic value in terms of BCR free survival. For drug resistance, we observe moderately diagnostic accuracy of EMTGPI score (AUC: 0.804). We found that PDCD1LG2 (p = 0.04) and CD96 (p = 0.01) expressed higher in BCR patients compared with their counterpart. For TME analysis, we detected that CD8+ T cells and M1 macrophages expressed higher in BCR group. Moreover, stromal score (p = 0.003), immune score (p = 0.01), and estimate score (p = 0.003) were higher in BCR patients. We found that EMTGPI was significantly related to HAVCR2 (r: 0.34), CD96 (r: 0.26), CD47 (r: 0.22), KIR3DL1 (r: −0.21), KLRD1 (r: −0.21), and CD2 (r: 0.21). In addition, we observed that EMTGPI was significantly associated with M1 macrophages (r: 0.6), M2 macrophages (r: −0.33), monocytes (r: −0.18), neutrophils (r: −0.43), CD8+ T cells (r: 0.13), and dendritic cells (r: 0.37). PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887.ConclusionsWe concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa.

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Secreted Frizzled-Related Protein 4 (SFRP4) Is an Independent Prognostic Marker in Prostate Cancers Lacking TMPRSS2: ERG Fusions

Cited by 9 publications

References 67 publications

EXPLORING THE ROLE OF sFRP-4, TFF-3, NF-кB AND ROMO1 LEVELS IN COLORECTAL CANCER: IMPLICATIONS FOR PATHOPHYSIOLOGY AND DISEASE PROGRESSION

EXPLORING THE ROLE OF sFRP-4, TFF-3, NF-кB AND ROMO1 LEVELS IN COLORECTAL CANCER: IMPLICATIONS FOR PATHOPHYSIOLOGY AND DISEASE PROGRESSION

Spatial transcriptomics reveals strong association between SFRP4 and extracellular matrix remodeling in prostate cancer

A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer

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