目的:探討SPARCL1表達(dá)對(duì)卵巢癌順鉑耐藥的影響,闡明SPARCL1表達(dá)與耐藥及預(yù)后的相關(guān)性。方法:RT-qPCR和Western blot法檢測(cè)卵巢癌細(xì)胞中SPARCL1表達(dá),免疫組化法（IHC）檢測(cè)卵巢癌組織中SPARCL1表達(dá),Kaplan-Meier生存曲線分析基因表達(dá)與無(wú)疾病生存期（DFS）和總生存期（OS）的關(guān)系。慢病毒轉(zhuǎn)染過(guò)表達(dá)或干擾基因在順鉑耐藥細(xì)胞SKOV3/DDP中的表達(dá),CCK-8法檢測(cè)細(xì)胞增殖并計(jì)算IC₅₀。轉(zhuǎn)錄組測(cè)序研究SPARCL1表達(dá)對(duì)卵巢癌細(xì)胞分子水平的影響。結(jié)果:與卵巢癌敏感組織相比,SPARCL1蛋白在耐藥組織中顯著低表達(dá)（P=0.001）,且該蛋白低表達(dá)能預(yù)測(cè)卵巢癌不良DFS（P=0.001）和OS（P=0.021）。SPARCL1在順鉑耐藥細(xì)胞SKOV3/DDP中顯著下調(diào)表達(dá),其過(guò)表達(dá)能減緩耐藥細(xì)胞增殖速度并提高對(duì)順鉑的敏感性,而干擾其表達(dá)則能加快細(xì)胞增殖并降低細(xì)胞對(duì)順鉑的敏感性。轉(zhuǎn)錄組測(cè)序結(jié)果發(fā)現(xiàn),SPARCL1過(guò)表達(dá)可能影響p53及細(xì)胞黏附分子等經(jīng)典卵巢癌耐藥調(diào)控通路。結(jié)論:SPARCL1低表達(dá)促進(jìn)耐藥且與不良OS和D... 

【文章來(lái)源】：現(xiàn)代婦產(chǎn)科進(jìn)展. 2020,29(04)北大核心CSCD

【文章頁(yè)數(shù)】：7 頁(yè)

【部分圖文】：

與空載細(xì)胞SKOV3/DDP-EV相比,SPARCL1過(guò)表達(dá)

圖6 與空載細(xì)胞SKOV3/DDP-EV相比,SPARCL1過(guò)表達(dá)表2 與空載細(xì)胞SKOV3/DDP-EV相比,SPARCL1過(guò)表達(dá) 細(xì)胞SKOV3/DDP-OE中上調(diào)和下調(diào)表達(dá)最顯著的基因列表 差異基因 上調(diào)/下調(diào) Fold Change(log2) P Padj FAM19A5 ↑ 4.60 1.90E-09 2.32E-06 SLC14A1 ↑ 3.26 3.87E-05 7.20E-03 VCAM1 ↑ 3.11 2.75E-05 5.61E-03 SCN3A ↑ 3.02 1.44E-05 3.39E-03 NTM ↑ 2.91 4.40E-05 7.76E-03 NPAS3 ↑ 2.68 1.48E-05 3.39E-03 EPHB1 ↑ 2.65 8.46E-06 2.34E-03 ELAVL3 ↑ 2.59 9.50E-06 2.53E-03 CADPS ↑ 2.51 1.47E-05 3.39E-03 VANGL2 ↑ 2.51 1.97E-05 4.22E-03 TNFRSF12A ↓ 2.52 3.79E-05 7.09E-03 閾值范圍:差異倍數(shù)≥2.5;P value和Padj value均≤0.01

表1 51例卵巢癌組織中SPARCL1表達(dá)與 臨床因素相關(guān)性分析 臨床因素 n SPARCL1表達(dá) P* 高表達(dá) 低表達(dá) 耐藥性 0.001 耐藥組 24(47.1) 7(29.2) 17(70.8) 敏感組 27(52.9) 21(77.8) 6(22.2) 年齡 0.267 <49歲 27(52.9) 17(63.0) 10(37.0) ≥49歲 24(47.1) 11(45.8) 13(54.2) 分期 0.305 I～I(xiàn)I 11(21.6) 8(72.7) 3(27.3) III～I(xiàn)V 40(78.4) 20(50.0) 20(50.0) 淋巴結(jié)轉(zhuǎn)移 0.232 無(wú) 16(31.4) 11(68.8) 5(31.3) 有 35(68.6) 17(48.6) 18(51.4) 腹腔轉(zhuǎn)移 0.305 無(wú) 11(21.6) 8(72.7) 3(27.3) 有 40(78.4) 20(50.0) 20(50.0) 血清CA125(U/ml) 0.782 <400 23(45.1) 12(52.2) 11(47.8) ≥400 28(54.9) 16(57.1) 12(42.9) *Pearson"s χ2檢驗(yàn)(雙側(cè))2.2 SPARCL1過(guò)表達(dá)能顯著提高卵巢癌耐藥細(xì)胞對(duì)順鉑的敏感性

【參考文獻(xiàn)】：
期刊論文
[1]SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer[J]. Shu-Jing Yu, Department of Radiation Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Science, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, Zhejiang Province, China Jie-Kai Yu, Wei-Ting Ge, Shu Zheng, Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Science, Zhejiang Province, China), the Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, Zhejiang Province, China Han-Guang Hu, Ying Yuan, Department of Medical Oncology, the Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, Zhejiang Province, China.  World Journal of Gastroenterology. 2011(15)



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