Zhao Yue, Sun Huimin, Zheng Jianzhong, Shao Chen, Zhang Dongwei
Department of Urology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Clinical Central Research Core, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Cell Biosci. 2021 Jan 6;11(1):5. doi: 10.1186/s13578-020-00517-w.
Goserelin is an effective alternative to surgery or estrogen therapy in prostate cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. However, not all users of goserelin can benefit from it, or some patients are not sensitive to goserelin. The advent of network pharmacology has highlighted the need for accurate treatment and predictive biomarkers. In this study, we successfully to identify 76 potential targets related to the compound of goserelin through network pharmacology approach. We also identified 18 DEGs in breast cancer tissues and 5 DEGs in cells, and 6 DEGs in prostate cancer tissues and 9 DEGs in cells. CRABP2 is the common DEG both in breast and prostate cancer. The risk prediction models constructed with potential prognostic targets of goserelin can successfully predict the prognosis in breast and prostate cancer, especially for very young breast cancer patients. Moreover, seven subgroups in breast cancer and six subgroups in prostate cancer were respectively identified based on consensus clustering using potential prognostic targets of goserelin that significantly influenced survival. The expression of representative genes including CORO1A and ANXA5 in breast and DPP4 in prostate showed strong correlations with clinic-pathological factors. Taken together, the novel signature can facilitate identification of new biomarkers which sensitive to goserelin, increase the using accuracy of goserelin and clarify the classification of disease molecular subtypes in breast and prostate cancer.
戈舍瑞林是前列腺癌姑息治疗中手术或雌激素治疗的有效替代方案,对于绝经前乳腺癌可能是卵巢切除术的有效替代方案。然而,并非所有使用戈舍瑞林的患者都能从中获益,或者有些患者对戈舍瑞林不敏感。网络药理学的出现凸显了精准治疗和预测性生物标志物的必要性。在本研究中,我们通过网络药理学方法成功鉴定出76个与戈舍瑞林化合物相关的潜在靶点。我们还在乳腺癌组织中鉴定出18个差异表达基因(DEG),在细胞中鉴定出5个DEG;在前列腺癌组织中鉴定出6个DEG,在细胞中鉴定出9个DEG。CRABP2是乳腺癌和前列腺癌中共同的DEG。利用戈舍瑞林潜在预后靶点构建的风险预测模型能够成功预测乳腺癌和前列腺癌的预后,尤其是对于非常年轻的乳腺癌患者。此外,基于戈舍瑞林潜在预后靶点的一致性聚类,分别在乳腺癌中鉴定出七个亚组,在前列腺癌中鉴定出六个亚组,这些亚组显著影响生存率。乳腺癌中包括CORO1A和ANXA5以及前列腺癌中DPP4等代表性基因的表达与临床病理因素显示出强相关性。综上所述,这种新的特征有助于识别对戈舍瑞林敏感的新生物标志物,提高戈舍瑞林的使用准确性,并明确乳腺癌和前列腺癌疾病分子亚型的分类。