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核心蛋白聚糖水平升高而非核心蛋白聚糖能预测早期前列腺癌的疾病进展。

Elevated levels of versican but not decorin predict disease progression in early-stage prostate cancer.

作者信息

Ricciardelli C, Mayne K, Sykes P J, Raymond W A, McCaul K, Marshall V R, Horsfall D J

机构信息

Department of Surgery, Flinders University School of Medicine, Flinders Medical Centre, Bedford Park, South Australia, Australia.

出版信息

Clin Cancer Res. 1998 Apr;4(4):963-71.

PMID:9563891
Abstract

Patients with clinically localized prostate cancer who might be cured by aggressive management are not easily identified using current clinical information. Additional, more accurate, biomarkers of tumor behavior need to be identified to improve clinical outcome. Our previous studies indicated that the concentration of the glycosaminoglycan chondroitin sulfate in prostatic stroma might be a useful biomarker of disease progression in early-stage prostate cancer. In this study, two chondroitin sulfate proteoglycans, versican and decorin, were investigated. Versican and decorin were immunolocalized to the periacinar and peritumoral fibromuscular stroma in sections of nonmalignant and malignant human prostate tissues. Video image measurements indicated that the concentrations of both proteoglycans were increased in the prostatic tissue of men with early-stage prostate cancer compared with tissue from men without cancer (P = 0.0006). Cox's univariate analysis indicated that increases in versican concentration but not in that of decorin were associated with increased risk of prostate-specific antigen (PSA) progression. Versican concentration was compared with other clinical or biological features of prognosis in two-variable regression analyses. Versican and serum PSA concentrations were independent predictors of PSA progression. Versican was a stronger prognostic factor than tumor grade, and it could predict outcome for patients with moderately differentiated tumors. Patients with low versican concentration had significantly better progression-free survival than patients with high levels of versican (Kaplan-Meier plot, 89% versus 27% PSA progression-free at 5 years, respectively; P = 0.0001). We conclude that the measurement of prostatic concentrations of versican, a molecule with reported anticellular adhesive properties, may be a useful marker of disease progression in patients with early-stage prostate cancer and that further study of versican in other patient cohorts is warranted.

摘要

目前的临床信息难以识别那些可能通过积极治疗治愈的临床局限性前列腺癌患者。需要识别出更多、更准确的肿瘤行为生物标志物,以改善临床结局。我们之前的研究表明,前列腺基质中糖胺聚糖硫酸软骨素的浓度可能是早期前列腺癌疾病进展的有用生物标志物。在本研究中,对两种硫酸软骨素蛋白聚糖,即多功能蛋白聚糖和核心蛋白聚糖进行了研究。在非恶性和恶性人类前列腺组织切片中,多功能蛋白聚糖和核心蛋白聚糖免疫定位在腺泡周围和肿瘤周围的纤维肌肉基质中。视频图像测量表明,与无癌男性的组织相比,早期前列腺癌男性的前列腺组织中这两种蛋白聚糖的浓度均升高(P = 0.0006)。Cox单因素分析表明,多功能蛋白聚糖浓度升高而非核心蛋白聚糖浓度升高与前列腺特异性抗原(PSA)进展风险增加相关。在双变量回归分析中,将多功能蛋白聚糖浓度与其他临床或生物学预后特征进行了比较。多功能蛋白聚糖和血清PSA浓度是PSA进展的独立预测因素。多功能蛋白聚糖是比肿瘤分级更强的预后因素,它可以预测中度分化肿瘤患者的结局。多功能蛋白聚糖浓度低的患者无进展生存期明显优于多功能蛋白聚糖水平高的患者(Kaplan-Meier曲线,5年时PSA无进展分别为89%和27%;P = 0.0001)。我们得出结论,测量具有报道的抗细胞黏附特性的多功能蛋白聚糖的前列腺浓度,可能是早期前列腺癌患者疾病进展的有用标志物,并且有必要在其他患者队列中对多功能蛋白聚糖进行进一步研究。

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