Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU - Norwegian University of Science and Technology, Trondheim, Norway.
Sci Rep. 2017 Oct 27;7(1):14276. doi: 10.1038/s41598-017-14622-3.
Increased knowledge of the molecular differences between indolent and aggressive prostate cancer is needed for improved risk stratification and treatment selection. Secreted frizzled-related protein 4 (SFRP4) is a modulator of the cancer-associated Wnt pathway, and previously suggested as a potential marker for prostate cancer aggressiveness. In this study, we investigated and validated the association between SFRP4 gene expression and aggressiveness in nine independent cohorts (n = 2157). By differential expression and combined meta-analysis of all cohorts, we detected significantly higher SFRP4 expression in cancer compared with normal samples, and in high (3-5) compared with low (1-2) Grade Group samples. SFRP4 expression was a significant predictor of biochemical recurrence in six of seven cohorts and in the overall analysis, and was a significant predictor of metastatic event in one cohort. In our study cohort, where metabolic information was available, SFRP4 expression correlated significantly with the concentrations of citrate and spermine, two previously suggested biomarkers for aggressive prostate cancer. SFRP4 immunohistochemistry in an independent cohort (n = 33) was not associated with aggressiveness. To conclude, high SFRP4 gene expression is associated with high Grade Group and recurrent prostate cancer after surgery. Future studies investigating the mechanistic and clinical usefulness of SFRP4 in prostate cancer are warranted.
需要更多地了解惰性和侵袭性前列腺癌之间的分子差异，以改善风险分层和治疗选择。分泌卷曲相关蛋白 4（SFRP4）是癌症相关 Wnt 通路的调节剂，先前被认为是前列腺癌侵袭性的潜在标志物。在这项研究中，我们在九个独立队列（n=2157）中研究并验证了 SFRP4 基因表达与侵袭性之间的关联。通过对所有队列的差异表达和合并荟萃分析，我们发现癌症组织中的 SFRP4 表达明显高于正常组织，而在高（3-5）分级组中明显高于低（1-2）分级组。SFRP4 表达是六个队列中七个队列和总体分析中生化复发的显著预测因子，在一个队列中是转移性事件的显著预测因子。在我们的研究队列中，有代谢信息可用，SFRP4 表达与柠檬酸和精胺的浓度显著相关，这两种物质之前被认为是侵袭性前列腺癌的生物标志物。在一个独立队列（n=33）中进行的 SFRP4 免疫组织化学分析与侵袭性无关。总之，高 SFRP4 基因表达与手术后高分级组和复发性前列腺癌有关。未来研究 SFRP4 在前列腺癌中的机制和临床应用价值是有必要的。
