Tawada Kakeru, Hayashi Hirokatsu, Endo Masahide, Horaguchi Takeshi, Yokoi Ryoma, Matsumoto Keita, Kuno Masashi, Fukada Masahiro, Asai Ryuichi, Sato Yuta, Yasufuku Itaru, Tajima Jesse Yu, Tanaka Yoshihiro, Takahashi Takao, Matsuhashi Nobuhisa, Tomita Hiroyuki
Department of Gastroenterological Surgery and Pediatric Surgery, Gifu University Graduate School of Medicine, Gifu, Gifu 501-1194, Japan.
Department of Surgery, Takayama Red Cross Hospital, Takayama, Gifu 506-0025, Japan.
Oncol Lett. 2025 Jun 19;30(2):402. doi: 10.3892/ol.2025.15148. eCollection 2025 Aug.
Syndecan-1 (SDC1), a transmembrane heparan sulfate proteoglycan that serves an important role in promoting tumorigenesis and metastasis, has been suggested as a potential biomarker for malignancy and as a therapeutic target. However, its role remains controversial because of its varying functions depending on carcinoma type and location. Elevated serum SDC1 levels after surgery have previously been associated with favorable disease-free survival (DFS). The present study aimed to clarify the role of SDC1 in resectable colorectal cancer (CRC) by evaluating its expression in tumor tissue, correlation with serum SDC1 levels and association with prognosis. In total, 46 patients who underwent radical surgery between July and December 2019 at Gifu University Hospital (Gifu, Japan) were included. The association between SDC1 expression in tumor tissues, assessed using immunohistochemical staining, and DFS was analyzed. Tumor tissue was compartmentalized into the membrane, cytoplasm and stroma. Staining intensity and percentage of positive cells were scored and categorized into two groups based on quartiles (Qs). The Q3-Q4 SDC1 staining scores for the membrane, cytoplasm and stroma were 30 (65.2%), 26 (56.6%) and 23 (50.0%) patients, respectively. Low SDC1 expression in all compartments was associated with advanced tumor stage (P=0.017, P=0.008 and P=0.035). In addition, low membranous SDC1 expression was associated with shorter DFS (P=0.013) and was an independent risk factor for recurrence (hazard ratio: 7.00, 95% confidence interval: 1.24-39.62, P=0.028). No significant correlation was observed between membranous SDC1 expression and serum SDC1 levels. The current study demonstrated that low membranous SDC1 expression may be an independent risk factor for recurrence and could serve as a prognostic biomarker for CRC. Furthermore, serum SDC1 levels may not depend solely on expression in tumor cells and are possibly influenced by multiple factors, including the tumor microenvironment and release from other tissues.
Syndecan-1（SDC1）是一种跨膜硫酸乙酰肝素蛋白聚糖，在促进肿瘤发生和转移中起重要作用，已被认为是恶性肿瘤的潜在生物标志物和治疗靶点。然而，由于其功能因癌症类型和位置而异，其作用仍存在争议。先前研究表明，术后血清SDC1水平升高与无病生存期（DFS）良好相关。本研究旨在通过评估SDC1在肿瘤组织中的表达、与血清SDC1水平的相关性以及与预后的关系，阐明SDC1在可切除结直肠癌（CRC）中的作用。总共纳入了2019年7月至12月在岐阜大学医院（日本岐阜）接受根治性手术的46例患者。分析了使用免疫组织化学染色评估的肿瘤组织中SDC1表达与DFS之间的关联。肿瘤组织被划分为膜、细胞质和基质。对染色强度和阳性细胞百分比进行评分，并根据四分位数（Qs）分为两组。膜、细胞质和基质的Q3-Q4 SDC1染色评分分别为30例（65.2%）、26例（56.6%）和23例（50.0%）患者。所有区域的低SDC1表达与肿瘤晚期相关（P=0.017、P=0.008和P=0.035）。此外，低膜SDC1表达与较短的DFS相关（P=0.013），并且是复发的独立危险因素（风险比：7.00，95%置信区间：1.24-39.62，P=0.028）。未观察到膜SDC1表达与血清SDC1水平之间存在显著相关性。当前研究表明，低膜SDC1表达可能是复发的独立危险因素，并且可作为CRC的预后生物标志物。此外，血清SDC1水平可能不仅仅取决于肿瘤细胞中的表达，还可能受到多种因素的影响，包括肿瘤微环境和其他组织的释放。
