Gene expression profile analysis identifies metastasis and chemoresistance-associated genes in epithelial ovarian carcinoma cells.

Gene expression profile analysis identifies metastasis and chemoresistance-associated genes in epithelial ovarian carcinoma cells.
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基因表达谱分析识别上皮性卵巢癌细胞中的转移和化疗耐药相关基因

DOI:
10.1007/s12032-014-0426-5
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发表时间:
2015-01
期刊:
Medical oncology (Northwood, London, England)
影响因子:
--
通讯作者:
Lin B
Lin B
中科院分区:
其他
文献类型:
--
作者:
Zhu L;Hu Z;Liu J;Gao J;Lin B

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本研究的目的是寻找与卵巢上皮性癌(EOC)细胞高转移能力和化疗耐药相关的基因。利用与41,000多个独特的人类基因和转录本互补的探针组的寡核苷酸芯片来确定基因表达谱是否可以区分三种上皮性卵巢细胞系(RMG-I-C、COC 1和HO 8910)与具有更高转移能力和化疗抗性的亚系(RMG-I-H、COCI/DDP和HO 8910/PM)。实时定量PCR和免疫组化染色验证了芯片结果。基因表达的系统聚类分析确定了49个基因表现出≥2.0倍的变化,P值≤0.05。在所有细胞系样品中通过定量PCR验证GCET 2、NLRP 4、FOXP 1和SNX 29基因的高度差异表达。最后,通过石蜡包埋的卵巢组织(即,对于转移,15例原发性EOC和10例大网膜转移[OM];对于化疗耐药性,13例敏感性EOC和13例耐药性EOC)。高转移能力和化疗耐药相关基因的鉴定可能为卵巢上皮性癌转移和化疗耐药的诊断和治疗提供新的分型特异性策略。
The purpose of this study was to identify genes that associated with higher ability of metastasis and chemotherapic resistance in epithelial ovarian carcinoma (EOC) cells. An oligonucleotide microarray with probe sets complementary to 41,000+unique human genes and transcripts was used to determine whether gene expression profile may differentiate three epithelial ovarian cell lines (RMG-I-C, COC1 and HO8910) from their sub-lines (RMG-I-H, COCI/DDP and HO8910/PM) with higher ability of metastasis and chemotherapic resistance. Quantitative real-time PCR and immunohistochemical staining validated the microarray results. Hierarchic cluster analysis of gene expression identified 49 genes that exhibited ≥2.0-fold change andPvalue ≤0.05. Highly differential expression of GCET2, NLRP4, FOXP1 and SNX29 genes was validated by quantitative PCR in all cell line samples. Finally, FOXP1 was validated at the protein level by immunohistochemistry in paraffin embedded ovarian tissues (i.e., for metastasis, 15 primary EOC and 10 omental metastasis [OM]; for chemoresistance, 13 sensitive and 13 resistant EOC). The identification of higher ability of metastasis and chemotherapic resistance-associated genes may provide a foundation for the development of new type-specific diagnostic strategies and treatment for metastasis and chemotherapic resistance in epithelial ovarian cancer.
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