Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Department of Urology, Qinghai University Affiliated Hospital, Qinghai University Medical College, Xining, Qinghai 810001, China.
Chin Med J (Engl). 2024 Aug 5;137(15):1844-1856. doi: 10.1097/CM9.0000000000002865. Epub 2023 Nov 24.
Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC ) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development.
We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC -relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1 ), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib.
GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1 , stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment.
GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC , regulated by E2F1 , acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.
尽管一些成熟的癌基因参与了癌症的发生和发展，如前列腺癌（PCa），但癌症基因的长尾仍有待确定。 Goosecoid（GSC）已被牵连到癌症的发展中。然而，GSC 在泛癌中的全面生物学作用，特别是在 PCa 中的作用，仍未被探索。本研究旨在研究 GSC 在 PCa 发展中的作用。
我们使用来自癌症基因组图谱（TCGA）、基因型组织表达（GTEx）、基因表达综合数据库（GEO）、德国癌症研究中心（DKFZ）和我们内部队列的数据，对 GSC 进行了系统的生物信息学探索。首先，我们评估了 GSC 的表达及其与患者预后的关联，并确定了癌症中与 GSC 相关的遗传改变。此外，我们专注于 GSC 在 PCa 中的临床特征和预后分析。为了了解 E2F 转录因子 1（E2F1）对 GSC 的转录调控，我们进行了染色质免疫沉淀定量聚合酶链反应（qPCR）。进行功能实验以验证 GSC 对肿瘤细胞表型和 trametinib 敏感性的影响。
GSC 在各种肿瘤中表达上调，与患者预后显著相关。GSC 的改变有助于各种肿瘤的进展，特别是在 PCa 中。GSC 表达较高的 PCa 患者无进展生存期和生化复发结局较差。此外，PCa 患者中 GSC 的上调大多伴有较高的 Gleason 评分、晚期肿瘤分期、淋巴结转移和前列腺特异性抗原（PSA）水平升高。机制上，转录因子 E2F1 通过结合其启动子区域刺激 GSC。详细的实验进一步表明，GSC 作为一种癌基因发挥作用，并影响 PCa 细胞对 trametinib 治疗的反应。
GSC 在 PCa 中高度过表达，与患者预后密切相关。我们发现，由 E2F1 调控的 GSC 作为一种癌基因，阻碍了 trametinib 在 PCa 中的治疗效果。
