Discovery of Proteins Responsible for Resistance to Three Chemotherapy Drugs in Breast Cancer Cells Using Proteomics and Bioinformatics Analysis.
Discovery of Proteins Responsible for Resistance to Three Chemotherapy Drugs in Breast Cancer Cells Using Proteomics and Bioinformatics Analysis.
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DOI：
10.3390/molecules27061762
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发表时间：
2022-03-08
期刊：
影响因子：
--
通讯作者：
Han D
中科院分区：
文献类型：
--
作者：
Cha HK;Cheon S;Kim H;Lee KM;Ryu HS;Han D
化疗耐药是对接受化疗的乳腺癌患者进行有效治疗的巨大障碍。虽然化疗耐药的机制已被广泛探讨，但在蛋白质组水平上的确切机制尚不清楚。特别是目前广泛应用的抗乳腺癌药物之间的比较研究非常有限。在这项研究中，我们采用蛋白质组学和生物信息学方法对化疗耐药乳腺癌细胞系进行研究，以了解阿霉素（DR）、紫杉醇（PR）和他莫昔芬（TAR）导致的潜在耐药机制。从三个TMT 6-plex和一个TMT 10-plex实验中，共鉴定和定量了10,385个蛋白质。生物信息学分析表明，Notch信号、免疫应答和蛋白重定位过程分别与DR、PR和TAR耐药具有独特的相关性。此外，与耐药相关的蛋白质组学特征被确定为许多fda批准的药物的潜在靶点。此外，我们确定了对总生存有显著影响的潜在预后蛋白。具有代表性的是，PLXNB2的表达与风险的显著增加相关，而ACOX3的下调与总生存率的降低相关。因此，我们的研究为乳腺癌化疗耐药的不同机制的蛋白质组学方面提供了新的见解。
Chemoresistance is a daunting obstacle to the effective treatment of breast cancer patients receiving chemotherapy. Although the mechanism of chemotherapy drug resistance has been explored broadly, the precise mechanism at the proteome level remains unclear. Especially, comparative studies between widely used anticancer drugs in breast cancer are very limited. In this study, we employed proteomics and bioinformatics approaches on chemoresistant breast cancer cell lines to understand the underlying resistance mechanisms that resulted from doxorubicin (DR), paclitaxel (PR), and tamoxifen (TAR). In total, 10,385 proteins were identified and quantified from three TMT 6-plex and one TMT 10-plex experiments. Bioinformatics analysis showed that Notch signaling, immune response, and protein re-localization processes were uniquely associated with DR, PR, and TAR resistance, respectively. In addition, proteomic signatures related to drug resistance were identified as potential targets of many FDA-approved drugs. Furthermore, we identified potential prognostic proteins with significant effects on overall survival. Representatively, PLXNB2 expression was associated with a highly significant increase in risk, and downregulation of ACOX3 was correlated with a worse overall survival rate. Consequently, our study provides new insights into the proteomic aspects of the distinct mechanisms underlying chemoresistance in breast cancer.
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影响因子：
7
作者：
Biswas D;Slade L;Duffley L;Mueller N;Dao KT;Mercer A;Pakkiriswami S;El Hiani Y;Kienesberger PC;Pulinilkunnil T
通讯作者：
Pulinilkunnil T
影响因子：
2.9
作者：
FETT, JW;STRYDOM, DJ;VALLEE, BL
通讯作者：
VALLEE, BL
DOI：
10.1073/pnas.1018858109
发表时间：
2012-10-30
影响因子：
11.1
作者：
Bailey, Shannon T.;Shin, Hyunjin;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
4.6
作者：
Ghebeh H;Al-Sayed A;Eiada R;Cabangon L;Ajarim D;Suleman K;Tulbah A;Al-Tweigeri T
通讯作者：
Al-Tweigeri T