Ovarian cancer is the leading cause of death from gynecologic malignancies. Cancer stem cells (CSC) seem to play a crucial role in tumor metastasis, recurrence, and chemoresistance. Therefore, CSCs offer significant potential for developing therapeutic targets and to understand tumor recurrence and chemoresistance mechanisms. In the present study, our aim was the identification of the gene group in ovarian CSCs (O-CSCs) and the potential of the resultant gene group in ovarian cancer prognosis. Two different microarray data sets were analyzed by comparing gene expression levels between O-CSCs and cancer samples. The O-CSC co-expression network was reconstructed and its modules were identified. According to the analysis results, 74 mutual DEGs were identified. The O-CSC-specific co-expression network included 32 nodes and 95 edges (network density: 19%), while the co-expression network in cancer samples was reconstructed with 74 nodes and 1066 edges (network density: 39%). Understanding of the molecular mechanism and signatures of O-CSCs should provide valuable insight into chemotherapy resistance and recurrence of ovarian tumors. A highly connected 12 gene module in O-CSC samples of BAMB1, NFKB12, EZR, TNFAIP3, C1orf86, PMAIP1, GEM, KHDRBS3, FILIP1, FGFR2, TGFBR3 and PEG10, (network density: 67%) was identified. Prognostic performance of these genes was evaluated independently using six ovarian cancer datasets (n = 1933 patient samples) via survival analysis. These co-expressed genes were determined as prognostic targets in ovarian cancer. Through literature search validation, five genes (C1orf86, PMAIP1, FILIP1, NFKB12 and PEG10) suggested as novel molecular targets in ovarian cancer. The presented prognostic biomarkers here provide a resource for the understanding of tumor recurrence and chemoresistance and may facilitate critical research directions and development of new prognostic and therapeutic strategies for ovarian cancer.

Abbreviations

CSCs: cancer stem cells; O-CSCs: ovarian CSCs; FACS: fluorescence-activated cell sorting; SP: side population; MP: main population; TFs: transcription factors.

中文翻译：

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卵巢癌干细胞中共表达的功能模块相关基因代表了卵巢癌中新的预后生物标志物。

卵巢癌是妇科恶性肿瘤死亡的主要原因。癌症干细胞（CSC）似乎在肿瘤转移，复发和化学耐药中起关键作用。因此，CSCs为开发治疗靶标以及了解肿瘤复发和化学耐药机制提供了巨大潜力。在本研究中，我们的目的是鉴定卵巢CSCs（O-CSCs）中的基因组以及所得基因组在卵巢癌预后中的潜力。通过比较O-CSC与癌症样品之间的基因表达水平，分析了两个不同的微阵列数据集。重建了O-CSC共表达网络，并确定了其模块。根据分析结果，确定了74个相互的DEG。特定于O-CSC的共表达网络包括32个节点和95个边缘（网络密度：19％），而在癌症样本中的共表达网络重建有74个节点和1066个边缘（网络密度：39％）。对O-CSCs的分子机制和特征的了解应该提供对化疗耐药性和卵巢肿瘤复发的有价值的见解。在BAMB1，NFKB12，EZR，TNFAIP3，C1orf86，PMAIP1，GEM，KHDRBS3，FILIP1，FGFR2，TGFBR3和PEG10的O-CSC样品中鉴定出高度连接的12基因模块（网络密度：67％）。通过生存分析，使用六个卵巢癌数据集（n = 1933个患者样品）独立评估了这些基因的预后性能。这些共同表达的基因被确定为卵巢癌的预后靶标。通过文献检索验证，五个基因（C1orf86，PMAIP1，FILIP1，NFKB12和PEG10）被认为是卵巢癌的新型分子靶标。

缩略语

CSC：癌症干细胞；O-CSC：卵巢CSC；FACS：荧光激活细胞分选；SP：边族；MP：主要人口；TF：转录因子。