Department of Gynecology and Obstetrics, Münster University Hospital, Albert-Schweitzer-Campus 1, 11, 48149, Münster, Germany.
Department of Bioinformatics, Semmelweis University, Budapest, Hungary.
J Cancer Res Clin Oncol. 2021 Jul;147(7):1937-1955. doi: 10.1007/s00432-021-03597-4. Epub 2021 Mar 19.
Dysregulated expression of proteoglycans influences the outcome and progression of numerous cancers. Several studies have investigated the role of individual glypicans in cancer, however, the impact of the whole glypican family of heparan sulfate proteoglycans on prognosis of a large patient cohort of breast cancer patients has not yet been investigated. In the present study, our aim was to investigate the prognostic power of the glypicans in breast cancer patients.
We used a public database including both gene expression data and survival information for 3951 breast cancer patients to determine the prognostic value of glypicans on relapse-free survival using Cox regression analysis. Moreover, we performed quantitative Real-Time PCR to determine glypican gene expression levels in seven representative breast cancer cell lines.
We found that high GPC3 levels were associated with a better prognosis in overall breast cancer patients. When stratified by hormone receptor status, we found that in worse prognosis subtypes low GPC1 levels correlate with a longer relapse-free survival, and in more favorable subtypes low GPC6 was associated with longer survival.
Our study concludes that glypicans could act as subtype-specific biomarkers for the prognosis of breast cancer patients and sparks hope for future research on glypicans possibly eventually providing targets for the treatment of the disease.
蛋白聚糖的表达失调会影响多种癌症的结局和进展。已有多项研究探讨了个别糖蛋白聚糖在癌症中的作用，但肝素硫酸蛋白聚糖整个糖蛋白聚糖家族对大量乳腺癌患者预后的影响尚未得到研究。在本研究中，我们旨在研究糖蛋白聚糖在乳腺癌患者中的预后价值。
我们使用包含 3951 例乳腺癌患者的基因表达数据和生存信息的公共数据库，通过 Cox 回归分析确定糖蛋白聚糖对无复发生存的预后价值。此外，我们还在 7 个有代表性的乳腺癌细胞系中进行了定量实时 PCR 以确定糖蛋白聚糖基因表达水平。
我们发现 GPC3 水平高与总体乳腺癌患者的预后较好相关。按激素受体状态分层时，我们发现预后较差的亚型中 GPC1 水平低与无复发生存时间延长相关，而在预后较好的亚型中 GPC6 水平低与生存时间延长相关。
我们的研究得出结论，糖蛋白聚糖可能是乳腺癌患者预后的特定亚型生物标志物，并为糖蛋白聚糖的未来研究带来希望，最终可能为该疾病的治疗提供靶点。
