Jönsson Jenny-Maria, Johansson Ida, Dominguez-Valentin Mev, Kimbung Siker, Jönsson Mats, Bonde Jesper Hansen, Kannisto Päivi, Måsbäck Anna, Malander Susanne, Nilbert Mef, Hedenfalk Ingrid
Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden.
Division of Oncology-Pathology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
PLoS One. 2014 Sep 16;9(9):e107643. doi: 10.1371/journal.pone.0107643. eCollection 2014.
Transcriptional profiling of epithelial ovarian cancer has revealed molecular subtypes correlating to biological and clinical features. We aimed to determine gene expression differences between malignant, benign and borderline serous ovarian tumors, and investigate similarities with the well-established intrinsic molecular subtypes of breast cancer.
Global gene expression profiling using Illumina's HT12 Bead Arrays was applied to 59 fresh-frozen serous ovarian malignant, benign and borderline tumors. Nearest centroid classification was performed applying previously published gene profiles for the ovarian and breast cancer subtypes. Correlations to gene expression modules representing key biological breast cancer features were also sought. Validation was performed using an independent, publicly available dataset.
5,944 genes were significantly differentially expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal-like breast cancer subtype were found. The benign and borderline serous tumors together were significantly correlated to the normal-like breast cancer subtype and the ovarian cancer signature derived from borderline tumors. The borderline tumors in the study dataset, in addition, also correlated significantly to the luminal A breast cancer subtype. These findings remained when analyzed in an independent dataset, supporting links between the molecular subtypes of ovarian cancer and breast cancer beyond those recently acknowledged.
These data link the transcriptional profiles of serous ovarian cancer to the intrinsic molecular subtypes of breast cancer, in line with the shared clinical and molecular features between high-grade serous ovarian cancer and basal-like breast cancer, and suggest that biomarkers and targeted therapies may overlap between these tumor subsets. The link between benign and borderline ovarian cancer and luminal breast cancer may indicate endocrine responsiveness in a subset of ovarian cancers.
上皮性卵巢癌的转录谱分析已揭示出与生物学和临床特征相关的分子亚型。我们旨在确定恶性、良性和交界性浆液性卵巢肿瘤之间的基因表达差异，并研究其与已明确的乳腺癌内在分子亚型的相似性。
使用Illumina的HT12 Bead Arrays对59例新鲜冷冻的浆液性卵巢恶性、良性和交界性肿瘤进行全基因表达谱分析。应用先前发表的卵巢癌和乳腺癌亚型的基因谱进行最近邻质心分类。还寻找了与代表乳腺癌关键生物学特征的基因表达模块的相关性。使用一个独立的公开可用数据集进行验证。
在良性和恶性浆液性卵巢肿瘤之间，有5944个基因存在显著差异表达，细胞周期过程在恶性亚组中富集。交界性肿瘤在两个簇之间分裂。发现恶性浆液性肿瘤与高侵袭性卵巢癌特征以及基底样乳腺癌亚型之间存在显著相关性。良性和交界性浆液性肿瘤共同与正常样乳腺癌亚型以及源自交界性肿瘤的卵巢癌特征显著相关。此外，研究数据集中的交界性肿瘤也与腔面A型乳腺癌亚型显著相关。在独立数据集中进行分析时，这些发现仍然成立，支持了卵巢癌和乳腺癌分子亚型之间超出最近认识的联系。
这些数据将浆液性卵巢癌的转录谱与乳腺癌的内在分子亚型联系起来，这与高级别浆液性卵巢癌和基底样乳腺癌之间共享的临床和分子特征一致，并表明这些肿瘤亚组之间的生物标志物和靶向治疗可能重叠。良性和交界性卵巢癌与腔面型乳腺癌之间的联系可能表明一部分卵巢癌具有内分泌反应性。
