Identification of candidate genes associated with tubal origin of high-grade serous ovarian cancer.
Identification of candidate genes associated with tubal origin of high-grade serous ovarian cancer.
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DOI：
10.3892/ol.2018.8346
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发表时间：
2018-05
期刊：
影响因子：
2.9
通讯作者：
Shi F
中科院分区：
文献类型：
--
作者：
Xiang L;Rong G;Zhao J;Wang Z;Shi F
有证据表明，高级别浆液性卵巢癌源自输卵管，而不是卵巢表面上皮。这被称为“输卵管起源”理论。本研究的目的是基于输卵管起源理论比较高级别浆液性卵巢癌（HGSOC）、输卵管上皮（FTE）和卵巢表面上皮（OSE）的免疫表型和基因表达谱，并鉴定与卵巢癌发生相关的差异基因。手术切除后共获得新鲜组织样本61例，其中HGSOC 21例、OSE 20例、FTE 20例。进行免疫染色来检测 PAX8 的表达，PAX8 被认为是苗勒管起源的潜在免疫表型标记。 Illumina BeadChip 用于基因表达谱分析。进行逆转录定量聚合酶链反应（RT-qPCR）以确认 HGSOC 和 FTE 之间候选基因的差异表达。本研究的结果表明，PAX8在HGSOC（19/21，90.4％）和FTE（20/20，100％）中高表达，但在OSE（3/20，14.3％）中不高表达。通过聚类分析生成的树状图表明 HGSOC 和 FTE 之间的基因表达谱相似性高于 OSE。 HGSOC 和 FTE 之间总共鉴定出 2,412 个差异表达基因（绝对倍数变化 >2），其中包括癌症中 822 个上调基因和 1,590 个下调基因。将S100钙结合蛋白P、Ras相互作用蛋白1、Wnt家族成员5A、肿瘤相关钙信号转导子2、Dickkopf Wnt信号通路抑制剂3和肿瘤抑制候选3基因确定为候选标志物，并通过RT-qPCR证实了其中HGSOC和FTE中差异基因表达（P<0.05）。结果表明，与OSE相比，HGSOC和FTE的免疫表型和基因表达谱存在更大的相似性，这与HGSOC的输卵管起源理论一致。
Evidence indicates that high-grade serous ovarian carcinoma arises from the fallopian tube, rather than ovarian surface epithelium. This is termed the ‘tubal origin’ theory. The aim of the present study was to compare the immunophenotype and gene expression profiling among high-grade serous ovarian carcinoma (HGSOC), fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) based on tubal origin theory, and identify the differential genes associated with ovarian carcinogenesis. A total of 61 cases of fresh tissue samples including 21 cases of HGSOC, 20 cases of OSE, and 20 cases of FTE were obtained following surgical resection. Immunostaining was performed to detect the expression of PAX8, which has been considered as a potential immunophenotype marker of Müllerian origin. Illumina BeadChip was applied for gene expression profiling. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the differential expression of candidate genes between HGSOC and FTE. The results of the present study demonstrated that PAX8 was highly expressed in HGSOC (19/21, 90.4%) and FTE (20/20, 100%), but not in OSE (3/20, 14.3%). A dendrogram generated by cluster analysis indicated a higher similarity of gene expression profile between HGSOC and FTE than OSE. A total of 2,412 differentially expressed genes were identified (absolute fold change >2) between HGSOC and FTE, including 822 upregulated genes in cancer and 1,590 downregulated genes. S100 calcium binding protein P, Ras-interacting protein 1, Wnt family member 5A, tumor-associated calcium signal transducer 2, Dickkopf Wnt signaling pathway inhibitor 3 and tumor suppressor candidate 3 genes were identified as candidate markers, of which the differential gene expression in HGSOC and FTE was confirmed by RT-qPCR (P<0.05). The results indicate the presence of a greater similarity in the immunophenotype and gene expression profile of HGSOC and FTE, when compared with OSE, which was consistent with the tubal origin theory of HGSOC.
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