ABSTRACT
Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ2=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.
Subject(s)
Male , Humans , Female , Adult , Middle Aged , Cross-Sectional Studies , Early Detection of Cancer/methods , Colorectal Neoplasms/pathology , Colonoscopy/methods , Mass Screening/methods , Adenoma/diagnosis , DNA , Syndecan-2/geneticsABSTRACT
BACKGROUND/AIMS: Syndecan-2 (SDC2) methylation was previously reported as a sensitive serologic biomarker for the early detection of colorectal cancer (CRC). The purpose of this study was to investigate whether SDC2 methylation is detectable in precancerous lesions and to determine the feasibility of using SDC2 methylation for the detection of CRC and precancerous lesions in bowel lavage fluid (BLF). METHODS: A total of 190 BLF samples were collected from the rectum at the beginning of colonoscopy from patients with colorectal neoplasm and healthy normal individuals. Fourteen polypectomy specimens were obtained during colonoscopy. A bisulfite pyrosequencing assay and quantitative methylation-specific polymerase chain reaction were conducted to measure SDC2 methylation in tissues and BLF DNA. RESULTS: SDC2 methylation was positive in 100% of villous adenoma (VA) and high-grade dysplasia, and hyperplastic polyp samples; 88.9% of tubular adenoma samples; and 0% of normal mucosa samples. In the BLF DNA test forSDC2 methylation, the sensitivity for detecting CRC and VA was 80.0% and 64.7%, respectively, at a specificity of 88.9%. The BLF of patients with multiple tubular adenomas, single tubular adenoma and hyperplastic polyps showed 62.8%, 26.7% and 28.6% rates of methylation-positive SDC2, respectively. CONCLUSIONS: Our results demonstrated that SDC2 methylation was a frequent event in precancerous lesions and showed high potential in BLF for detecting patients with colorectal neoplasm.
Subject(s)
Humans , Adenoma , Adenoma, Villous , Colonoscopy , Colorectal Neoplasms , DNA , Feces , Methylation , Mucous Membrane , Polymerase Chain Reaction , Polyps , Rectum , Sensitivity and Specificity , Syndecan-2 , Therapeutic IrrigationABSTRACT
<p><b>OBJECTIVE</b>To explore the associations between the genetic variations in the SDC2 gene and overall survival and risk of radiation esophagitis in patients with esophageal squamous cell carcinoma (ESCC).</p><p><b>METHODS</b>Eleven functional haplotype-tagging single nucleotide polymorphisms (htSNPs) of SDC2 were genotyped in 296 ESCC patients who received radiotherapy alone, and had different response and esophagitis. The associations between genotypes and risk of esophagitis were measured by odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for sex, age, tumor location, staging, radiotherapy mode and total radiation dose. The hazard ratios (HRs) were estimated using Cox proportional hazards regression model.</p><p><b>RESULTS</b>The median survival time (MST) of these patients was 14 months. Of them, 260 (87.8%) had died until the last date of follow-up of 30 June, 2014. Clinical stage (stage IV vs. stage II) and total radiation dose (≥ 60 Gy vs. < 60 Gy) influence the overall survival time of the patient significantly. Cox proportional hazards regression model analysis showed that the subjects with rs61599409 T allele had an decreased hazard ratio as compared with those with C allele (adjusted HR = 0.82, 95% CI, 0.66-1.02), but the difference was not statistically significant (P = 0.071). The rest 10 htSNPs were not associated with the overall survival of ESCC patients treated with radiotherapy. Among this set of patients, 160 (54.1%) suffered from radiation esophagitis. We found that rs17788084 A > T SNP in the 3'-untranslational region of SDC2 was associated with esophagitis risk, with the OR being 0.48 (95% CI = 0.28-0.85, P = 0.011) for the TA or TT genotype compared with the AA genotype.</p><p><b>CONCLUSIONS</b>These results suggest that rs17788084 genetic variation in SDC2 is associated with risk of radiation esophagitis and might serve as a potential biomarker for personalized radiotherapy of ESCC.</p>
Subject(s)
Humans , Alleles , Carcinoma, Squamous Cell , Mortality , Pathology , Radiotherapy , Esophageal Neoplasms , Mortality , Pathology , Radiotherapy , Esophagitis , Genetics , Genetic Variation , Genotype , Haplotypes , Odds Ratio , Polymorphism, Single Nucleotide , Proportional Hazards Models , Radiation Injuries , Genetics , Radiotherapy Dosage , Risk , Survival Analysis , Syndecan-2 , Genetics , Time FactorsABSTRACT
BACKGROUND: Melanoma is a malignant neoplasm originating from melanocytes. It has been recently suggested that syndecan-2 may contribute to the aggressive phenotype and metastatic potential of melanoma in cell line studies. However, there is no quantitative analysis of syndecan-2 expression using human melanoma tissue. OBJECTIVE: This study aimed to examine the specific expression of syndecan-2 in human melanoma tissue. METHODS: A total of 35 sections of formalin-fixed, paraffin-embedded tissues were investigated for syndecan-2 expression using immunohistochemical staining. Also, a total of 6 tissues and two kinds of cell lines were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and western blot. RESULTS: Immunohistochemical staining of 23 cases of melanoma tissue was done, and in 5 cases (21.7%), strong expression of syndecan-2 was seen. Also, syndecan-2 was detected in human melanoma tissue and MNT-1 melanoma cells by RT-PCR and western blot analysis. CONCLUSION: We suggest that syndecan-2 expression is increased in melanoma compared to nevus. The results of this study may help to explain the clinical features of melanoma and syndecan-2.