Perez-Ortiz Andric C, Ramírez Israel, Cruz-López Juan C, Villarreal-Garza Cynthia, Luna-Angulo Alexandra, Lira-Romero Esmeralda, Jiménez-Chaidez Salvador, Díaz-Chávez José, Matus-Santos Juan A, Sánchez-Chapul Laura, Mendoza-Lorenzo Patricia, Estrada-Mena Francisco J
Universidad Panamericana, Escuela de Medicina, Mexico City, Mexico.
Yale University School of Public Health, Laboratory of Epidemiology and Public Health, New Haven, CT, USA.
Oncotarget. 2017 Nov 15;8(63):106454-106467. doi: 10.18632/oncotarget.22461. eCollection 2017 Dec 5.
Locally advanced breast cancer (LABC) cases have a varying five-year survival rate, mainly influenced by the tumor response to chemotherapy. Paclitaxel activity (response rate) varies across populations from 21.5% to 84%. There are some reports on genetic traits and paclitaxel; however, there is still considerable residual unexplained variability. In this study, we aimed to test the association between eleven novel markers and tumor response to paclitaxel and to explore if any of them influenced tumor protein expression. We studied a cohort of 140 women with LABC. At baseline, we collected a blood sample (for genotyping), fine needle aspirates (for Western blot), and tumor measurements by imaging. After follow-up, we ascertained the response to paclitaxel monotherapy by comparing the percent change in the pre-, post- tumor measurements after treatment. To allocate exposure, we genotyped eleven SNPs with TaqMan probes on RT-PCR and regressed them to tumor response using linear modeling. In addition, we compared protein expression, between breast tumors and healthy controls, of those genes whose genetic markers were significantly associated with tumor response. After adjusting for multiple clinical covariates, SNPs on the , , and genes were significant independent predictors of poor tumor response (tumor growth) despite paclitaxel treatment. Moreover, proteins encoded by those genes are significantly downregulated in breast tumor samples.
局部晚期乳腺癌（LABC）病例的五年生存率各不相同，主要受肿瘤对化疗反应的影响。紫杉醇活性（缓解率）在不同人群中从21.5%到84%不等。关于遗传特征和紫杉醇已有一些报道；然而，仍存在相当大的无法解释的残余变异性。在本研究中，我们旨在测试11个新标记与肿瘤对紫杉醇反应之间的关联，并探讨其中是否有任何一个影响肿瘤蛋白表达。我们研究了140例LABC女性队列。在基线时，我们采集了血样（用于基因分型）、细针穿刺抽吸物（用于蛋白质印迹法）以及通过影像学测量肿瘤。随访后，我们通过比较治疗前后肿瘤测量值的变化百分比来确定对紫杉醇单药治疗的反应。为了分配暴露情况，我们使用TaqMan探针在RT-PCR上对11个单核苷酸多态性（SNP）进行基因分型，并使用线性模型将它们与肿瘤反应进行回归分析。此外，我们比较了遗传标记与肿瘤反应显著相关的那些基因在乳腺肿瘤和健康对照之间的蛋白表达。在调整了多个临床协变量后，尽管进行了紫杉醇治疗，但位于 、 和 基因上的SNP是肿瘤反应不良（肿瘤生长）的显著独立预测因子。此外，这些基因编码的蛋白在乳腺肿瘤样本中显著下调。
