Bååth Maria, Westbom-Fremer Sofia, Martin de la Fuente Laura, Ebbesson Anna, Davis Juliette, Malander Susanne, Måsbäck Anna, Kannisto Päivi, Hedenfalk Ingrid
Division of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden.
Department of Surgical Pathology, Division of Laboratory Medicine, Skåne University Hospital, Lund, Sweden.
Mol Cell Oncol. 2020 Sep 5;7(6):1805094. doi: 10.1080/23723556.2020.1805094.
The transcription factor SOX2 is a well-established and important stem cell marker. Its role in cancer biology remains unclear, but it has been proposed to also be a marker of cancer stem cells. We investigated the role of SOX2 protein expression in women with high-grade serous ovarian cancer (HGSOC) to determine its potential prognostic and treatment predictive value. We constructed a tissue microarray of 130 advanced stage HGSOC tumors with an average of 6 cores each, stained for SOX2 protein expression and evaluated survival outcomes. We also treated two HGSOC cell lines with carboplatin and paclitaxel and measured SOX2 expression by RT-PCR and immunoblotting at different doses and time-points. Among patients with non-radical debulking surgery overall and progression-free survival were shorter for patients with SOX2 positive tumors (mean 26 . 39 months, log-rank test: = .0076, and mean 14 . 19 months, = .055, respectively). Knockdown of in cell lines did not affect growth inhibition following chemotherapy treatment. Our results show that SOX2 has a strong prognostic potential among HGSOC patients with residual tumor tissue after debulking surgery and suggest that SOX2 expressing cells remaining after non-radical debulking surgery may constitute a subpopulation of cancer stem cells with greater tumor-initiating potential.
转录因子SOX2是一种公认的重要干细胞标志物。其在癌症生物学中的作用尚不清楚,但有人提出它也是癌症干细胞的标志物。我们研究了SOX2蛋白表达在高级别浆液性卵巢癌(HGSOC)女性患者中的作用,以确定其潜在的预后和治疗预测价值。我们构建了一个包含130个晚期HGSOC肿瘤的组织微阵列,每个肿瘤平均有6个核心,对SOX2蛋白表达进行染色,并评估生存结果。我们还用卡铂和紫杉醇处理了两种HGSOC细胞系,并在不同剂量和时间点通过RT-PCR和免疫印迹法测量SOX2的表达。在接受非根治性减瘤手术的患者中,SOX2阳性肿瘤患者的总生存期和无进展生存期较短(分别为平均26.39个月,对数秩检验:P = 0.0076;平均14.19个月,P = 0.055)。在细胞系中敲低SOX2并不影响化疗后的生长抑制。我们的结果表明,SOX2在减瘤手术后有残留肿瘤组织的HGSOC患者中具有很强的预后潜力,并表明非根治性减瘤手术后残留的表达SOX2的细胞可能构成具有更大肿瘤起始潜力的癌症干细胞亚群。