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INTRODUCTION:Noninvasive stool DNA-based methylation testing has emerged as an effective strategy for the early colorectal cancer (CRC) detection. Syndecan-2 (SDC2) methylation frequently occurs in all stages of CRC; therefore, the aim of this study was to evaluate the clinical performance of a stool DNA-based SDC2 methylation test for detecting CRC in asymptomatic or high-risk CRC populations.METHODS:This multicenter prospective study was conducted to determine the clinical performance of the SDC2 methylation test on stool DNA using real-time polymerase chain reaction. Stool samples were collected from asymptomatic individuals before colonoscopy, and the test results were independently analyzed through comparison with colonoscopic findings and pathological outcomes as reference standards.RESULTS:Of the 1,124 evaluable participants, 20 had CRC, 73 had advanced adenomatous polyps (≥1.0 cm), 469 had nonadvanced adenomatous polyps (<1.0 cm), 178 had non-neoplastic polyps, and 384 had negative colonoscopy results. The stool SDC2 methylation test had a sensitivity and specificity of 95.0% and 81.5%, respectively, for detecting CRC, while the sensitivity for detecting advanced adenomatous polyps and CRC was 58.1%. The rate of adenoma detection increased with polyp size (P < 0.01), and sensitivity was not associated with CRC stage (P = 0.864).DISCUSSION:The stool DNA-based SDC2 methylation test attained a high sensitivity for CRC detection in an asymptomatic high-risk population. Further large-scale clinical studies are required to validate the clinical utility of this test as a population-based CRC screening tool.

Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 ( SDC2 ) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. C T values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration : This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1 .

Background Colorectal cancer (CRC) screening can effectively reduce disease-related mortality by detecting CRC at earlier stages. We have previously demonstrated that the presence of SDC2 methylation in stool DNA is significantly associated with the occurrence of CRC regardless of clinical stage. The aim of this study was to evaluate the clinical performance of stool DNA-based SDC2 methylation test for CRC. Methods Aberrant SDC2 methylation in stool-derived DNA was measured by linear target enrichment (LTE)-quantitative methylation-specific real-time PCR (qMSP). Duplicate reactions of me SDC2 LTE-qMSP test were performed for stool samples obtained from CRC patients representing all stages (0–IV) and asymptomatic individuals who were subsequently underwent colonoscopy examination. To determine the diagnostic value of test in CRC and control groups, sensitivity and specificity were evaluated by receiver operating characteristic curve analysis. Results Of 585 subjects who could be evaluated, 245 had CRC, 44 had various sizes of adenomatous polyps, and 245 had negative colonoscopy results. Stool DNA-based me SDC2 LTE-qMSP showed an overall sensitivity of 90.2% with AUC of 0.902 in detecting CRC (0–IV) not associated with tumor stage, location, sex, or age ( P  > 0.05), with a specificity of 90.2%. Sensitivity for detecting early stages (0-II) was 89.1% (114/128). This test also detected 66.7% (2/3) and 24.4% (10/41) of advanced and non-advanced adenomas, respectively. Conclusions Results of this study validated the capability of stool DNA based- SDC2 methylation test by LTE-qMSP for early detection of CRC patient with high specificity. Trial registration ClinicalTrials.gov, NCT03146520 , Registered 10 May 2017, Retrospectively registered; however, control arm was prospectively registered.

Lymph node metastasis (LNM) is a pivotal determinant of breast cancer (BC) patient prognosis and treatment efficacy. Cell surface heparan sulfate proteoglycans (HSPGs), namely, syndecan-1 (SDC1), SDC2, and SDC4, are involved in cancer progression, metastasis, and regulate extracellular vesicles (EVs) biogenesis, including the microvesicles (MVs). This study analyzed MV-enriched EVs isolated from blood plasma of BC patients with negative ( n  = 19) and positive ( n  = 20) LNM (nLNM and pLNM, respectively) using differential centrifugation. Western blot analysis revealed significantly elevated SDC2 levels in MV-enriched EVs from pLNM cases compared to nLNM. Additionally, fibronectin (FN), a SDC2-interacting protein identified through STRING analysis, was also upregulated in pLNM MV-enriched EVs. In contrast, qRT-PCR showed reduced SDC2 ( P  < 0.01) and FN ( P  < 0.05) mRNA levels in tumor tissues of pLNM patients compared to nLNM. ROC analysis highlighted the diagnostic value of SDC2 (AUC: 0.8376) and FN (AUC: 0.8803) mRNA in differentiating LNM status. Bioinformatics analyses further confirmed the association of SDC2 and FN expression with BC staging and prognosis. These findings underscore the potential of circulating MV-enriched EV-associated SDC2 and FN, along with their tumor tissue mRNA expression, as potential predictive biomarkers for LNM and chemotherapy response in chemotherapy-naïve obese BC patients.

Purpose To investigate the association between Syndecan-2 gene methylation and protein expression dynamics in colorectal cancer and evaluate its clinicopathological significance. Methods We analyzed 197 tissues (96 colorectal cancer, 64 adenoma, and 37 normal tissues). Syndecan-2 methylation was quantified using quantitative methylation-specific polymerase chain reaction, and protein expression was evaluated via immunohistochemistry. Results Syndecan-2 methylation frequency was significantly higher in colorectal cancer (81.25%) and adenoma (64.06%) than in normal (5.41%) tissues. It showed high diagnostic accuracy for colorectal cancer (area under the curve = 0.88). Although methylation status was unrelated to most clinical parameters, higher methylation levels were correlated with poor tumor differentiation (p = 0.022). Syndecan-2 protein was aberrantly expressed in tumor stroma but lacked clinical correlations. A significant positive correlation between methylation and protein expression was observed across the sample (p < 0.05); however, this association was not maintained within the colorectal cancer subgroup specifically, showing no intrasample concordance (Kappa statistic = −0.046). Conclusion Syndecan-2 methylation serves as a highly sensitive epigenetic biomarker for the early detection of colorectal cancer. The findings reveal a complex and heterogeneous relationship between Syndecan-2 methylation and its protein expression during colorectal cancer progression, suggesting stage-specific regulatory mechanisms. Further multiomics studies are warranted to elucidate the underlying functional dynamics.

Plasma DNA methylation SEPTIN9 , Syndecan 2 ( SDC2 ), and Branched Chain Amino Acid Transaminase 1 ( BCAT1 ) tests have served as valuable diagnostic, prognostic, and predictive markers for colorectal cancer (CRC). In this study, we analyzed data including 104 eligible CRC patients, 138 colorectal benign diseases, and 106 healthy subjects in our hospital from January 2019 to May 2023. This study was approved by the Medical Ethics Committee of Henan Cancer Hospital (Approval No.2018156). A real-time polymerase chain reaction-based gene panel was used to detect the methylation of SEPTIN9 , SDC2 , and BCAT1 . The composite score (P) was calculated according to the cycle threshold (Ct) values of the three methylated genes using the logistic regression equation. The consistency of assay and pathological diagnosis were evaluated with kappa analyzed by IBM SPSS Statistics. The median survival time was obtained by Kaplan-Meier survival analysis. Statistical figures were all carried out using Origin software. The three genes were found to be significantly methylated in ctDNA of CRC patients compared to patients with colorectal benign diseases and healthy controls. The sensitivity was 86.1%, the specificity was 97.6%, and the area under the curve of 0.929. Positive predictive value (PPV) was 57.2%, and Negative predictive value (NPV) was 99.5%. No statistically significant differences in diagnostic efficiency were observed in relation to different types of stages. Moreover, there was a significant difference in the expression of composite scores between survival periods greater than 1 year and less than 1 year ( p  < 0.01). The composite score (P) derived from the ctDNA methylation levels of SEPTIN9 , SDC2 , and BCAT1 can be used for CRC diagnosis with high sensitivity and specificity. A combination of ctDNA methylation was proved to be an effective diagnostic, prognostic, and predictive biomarker in colorectal cancer.

Interstitial cystitis/bladder pain syndrome (IC/BPS) plagues patients and clinicians with its unclear etiology and pathogenesis, and ineffective treatments. Destruction of epithelial tissue and proliferation of interstitial tissue are typical pathological features of IC/BPS, in which epithelial-mesenchymal transition (EMT) may play an important role. Both the increased urination frequency observed in mice with acute cystitis induced by cyclophosphamide (CYP) and the disruption of the anti-leakage barrier in urothelial cells induced by LPS are associated with the occurrence of EMT. The expression of heparanase 1 (HPSE) and syndecan-2 (SDC-2) is up-regulated in the bladder mucosa of patients with IC, and both of them can promote the development of EMT. Improvement of lower urinary tract symptoms and restoration of the uroepithelial cell anti-leakage barrier in mice with CYP-induced cystitis after treatment with the HPSE inhibitor OGT2115 and inhibited the development of EMT. We then verified that HPSE binds to SDC-2 and that SDC-2 is a key intermediate protein in the pro-EMT role of HPSE, and that EMT was inhibited by knockdown of SDC-2. SDC-2 exerts its biological function by inhibiting the ubiquitinated degradation of TGF-βR1. Here we identified a novel mechanism by which the HPSE/ SDC-2 axis promotes EMT development and thus causes epithelial dysfunction and altered voiding behavior, providing a new direction for the treatment of IC/BPS.

Background The high incidence of recurrence and metastatic disease remain the major issues for papillary thyroid cancer (PTC) patients. Previous studies have demonstrated that Syndecan-2 (SDC2) plays a key role in multiple cancers progression. However, the potential role of SDC2 in PTC progression and recurrence remains unclear. Methods First, we performed bioinformatics analysis and western-blotting analysis to explore the potential prognostic value of SDC2 in PTC. Then we applied transient siRNA knockdown and plasmid overexpression to alter SDC2 expression level in PTC cell line B-CPAP and KTC-1. After that, we carried out scratch wound healing assay, transwell assay and cell counting kits-8 (CCK8) assay to explore the cell migration, invasiveness and viability. We also explored expressions of mesenchymal and epithelial markers, multiple thyroids differentiating markers and hedgehog signaling members to address the potential underlying mechanisms. Results Firstly, we found a significant negative correlation of SDC2 expression with advanced disease characters in PTC. Then bioinformatic analysis indicated the SDC2 expression was closely related to multiple key pathways and thyroid differentiation markers. Targeting SDC2 expression significantly influenced the growth and invasion of PTC cells according to series of assays. Western-blotting results of α-SMA and ZO-1 also indicated the altered EMT process. Furthermore, attenuated SDC2 expression also leads to the PTC de-differentiation, which could be due to hedgehog signaling alteration. Conclusions Our findings suggest that SDC2 would be a promising therapy target for advanced radioiodine refractory thyroid cancer, but the role in PTC progression is complicated and requires further exploration.

Colorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, including both unfractioned and supernatant urine fractions, of 92 CRC patients and 63 healthy volunteers were analyzed for DNA methylation levels of 6 CRC-associated markers ( SEPT9 , TMEFF2 , SDC2 , NDRG4 , VIM and ALX4 ). Optimal marker panels were determined by two statistical approaches. Methylation levels of SEPT9 were significantly increased in urine supernatant of CRC patients compared to controls ( p  < 0.0001). Methylation analysis in unfractioned urine appeared inaccurate. Following multivariate logistic regression and classification and regression tree analysis, a marker panel consisting of SEPT9 and SDC2 was able to detect up to 70% of CRC cases in urine supernatant at 86% specificity. First evidence is provided for CRC detection in urine by SEPT9 methylation analysis, which combined with SDC2 allows for an optimal differentiation between CRC patients and controls. Urine therefore provides a promising liquid biopsy for non-invasive CRC detection.

Colorectal cancer (CRC) is one of the most common cancers in the western world. Screening is an efficient method of reducing cancer-related mortality. Molecular biomarkers for cancer in general and CRC in particular have been proposed, and hypermethylated DNA from stool or blood samples are already implemented as biomarkers for CRC screening. We aimed to evaluate the performance of proven hypermethylated DNA promoter regions as plasma based biomarkers for CRC detection. We conducted a cross-sectional case-control study of 193 CRC patients and 102 colonoscopy-verified healthy controls. Using methylation specific polymerase chain reaction, we evaluated 30 DNA promoter regions previously found to be CRC specific. We used multivariable logistic regression with stepwise backwards selection, and subsequent leave-pair-out cross validation, to calculate the optimism corrected area under the receiver operating characteristics curve (AUC) for all stage as well as early stage CRC. None of the individual DNA promoter regions provided an overall sensitivity above 30% at a reasonable specificity. However, seven hypermethylated promoter regions (ALX4, BMP3, NPTX2, RARB, SDC2, SEPT9, and VIM) along with the covariates sex and age yielded an optimism corrected AUC of 0.86 for all stage CRC and 0.85 for early stage CRC. Overall sensitivity for CRC detection was 90.7% at 72.5% specificity using a cut point value of 0.5. Individual hypermethylated DNA promoter regions have limited value as CRC screening markers. However, a panel of seven hypermethylated promoter regions show great promise as a model for CRC detection.