Cancer Center, Faculty of Health Sciences, University of Macau, Macau, China.
Metabolomics Core, Faculty of Health Sciences, University of Macau, Macau, China.
Clin Cancer Res. 2017 Dec 1;23(23):7400-7411. doi: 10.1158/1078-0432.CCR-17-0638. Epub 2017 Sep 22.
The relative importance of fallopian tube (FT) compared with ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs. A collection of transcriptome data of 80 FTs, 89 OSEs, and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and OSE-like tumors. A molecular signature was developed for identifying tissue origin of SOC and then was used to reevaluate the prognostic genes and therapeutic biomarkers of SOC of different tissue origins. IHC staining of tissue array and functional experiments on a panel of ovarian cancer cell lines were used to further validate the key findings. The expression patterns of tissue-specific genes, prognostic genes, and molecular markers all support a dualistic tissue origin of SOC, from either FT or OSE. A molecular signature was established to identify the tissue identity of SOCs. Surprisingly, the signature showed a strong association with overall survival (OSE-like vs. FT-like, HR = 4.16; 95% CI, 2.67-6.48; < 10). The pharmacogenomic approach revealed AXL to be a therapeutic target of the aggressive OSE-derived SOC. SOC has two subtypes originated from either FT or OSE, which show different clinical and pathologic features. .
输卵管（FT）与卵巢表面上皮（OSE）在浆液性卵巢癌（SOC）发生中的相对重要性仍未确定。在这里，我们采用综合方法研究 SOC 的组织起源及其与临床结局和治疗药物反应的关系。系统分析了 80 个 FT、89 个 OSE 和 2668 个 SOC 的转录组数据集，以确定类似于 FT 和 OSE 的肿瘤的特征。开发了一种用于识别 SOC 组织起源的分子特征，然后用于重新评估不同组织起源的 SOC 的预后基因和治疗生物标志物。通过对组织阵列的免疫组化染色和一系列卵巢癌细胞系的功能实验进一步验证了关键发现。组织特异性基因、预后基因和分子标记的表达模式均支持 SOC 的二元组织起源，来源于 FT 或 OSE。建立了一个分子特征来识别 SOC 的组织身份。令人惊讶的是，该特征与总生存期（OSE 样与 FT 样，HR=4.16；95%CI，2.67-6.48； < 10）具有很强的关联性。药物基因组学方法表明 AXL 是侵袭性 OSE 衍生 SOC 的治疗靶点。SOC 有两种亚型，来源于 FT 或 OSE，表现出不同的临床和病理特征。
