Microarray-based identification of genes associated with prognosis and drug resistance in ovarian cancer
Microarray-based identification of genes associated with prognosis and drug resistance in ovarian cancer
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基于微阵列的卵巢癌预后和耐药相关基因的鉴定
DOI：
10.1002/jcb.27892
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发表时间：
2019-04-01
影响因子：
4
通讯作者：
Liu, Xia
中科院分区：
文献类型：
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作者：
Yin, Fuqiang;Yi, Shang;Liu, Xia
由于耐药，卵巢癌（OC）患者的预后较差。因此，有必要确定影响卵巢癌耐药和预后的因素。在本研究中，与197个敏感组织相比，我们在90个铂耐药OC组织中鉴定出131个基因显著失调，其中30个与癌症基因组图谱队列中489例OC患者的无病生存（DFS; n = 16）、总生存（OS; n = 6）或两者（n = 8）显著相关。在这30个基因中，在90个耐药组织中，17个基因显著上调，13个基因显著下调，除了一个例外，耐药组织中所有上调/下调的基因都是缩短DFS或/和OS的预测因子。LAX1、MECOM和PDIA4是DFS的独立危险因素，KLF1、SLC7A11和PDIA4是OS的独立危险因素；结合这些基因比单独使用任何基因都能更准确地预测DFS和OS。我们进一步验证了51例OC患者（24例耐药患者和27例敏感患者）PDIA4蛋白的下调，证实PDIA4蛋白下调可预测DFS和OS。PDIA4在1656例OC患者的更大样本中也一致预测OS。这30个基因，特别是PDIA4，可能是治疗OC的治疗靶点或生物标志物。
The outcome for patients with ovarian cancer (OC) is poor because of drug resistance. Therefore, identification of factors that affect drug resistance and prognosis in OC is needed. In the present study, we identified 131 genes significantly dysregulated in 90 platinum-resistant OC tissues compared with 197 sensitive tissues, of which 30 were significantly associated with disease-free survival (DFS; n = 16), overall survival (OS; n = 6), or both (n = 8) in 489 OC patients of the The Cancer Genome Atlas cohort. Of these 30 genes, 17 were significantly upregulated and 13 were downregulated in the 90 resistant tissues, and with one exception, all of the up-/downregulated genes in resistant tissues were predictors of shorter DFS or/and OS. LAX1, MECOM, and PDIA4 were independent risk factors for DFS, and KLF1, SLC7A11, and PDIA4 for OS; combining these genes provided more accurate predictions for DFS and OS than any of the genes used individually. We further verified downregulation of PDIA4 protein in 51 specimens of patients with OC (24 drug resistant's and 27 sensitive's), which confirmed that downregulated PDIA4 predicted DFS and OS. PDIA4 also consistently predicted OS in a larger sample of 1656 patients with OC. These 30 genes, particularly the PDIA4, could be therapeutic targets or biomarkers for managing OC.