Class III β-tubulin Expression in Colorectal Neoplasms Is a Potential Predictive Biomarker for Paclitaxel Response
Class III β-tubulin Expression in Colorectal Neoplasms Is a Potential Predictive Biomarker for Paclitaxel Response
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DOI：
10.21873/anticanres.13160
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发表时间：
2019-02-01
影响因子：
2
通讯作者：
Akyol, Aytekin
中科院分区：
文献类型：
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作者：
Oztop, Sidika;Isik, Aynur;Akyol, Aytekin
背景/目的：结直肠癌（CRC）治疗的挑战包括预后和药物反应或化疗耐药的预测。本研究旨在研究β iii -微管蛋白（TUBB3）是否存在于各种类型的正常组织和癌症中，是结直肠肿瘤对紫杉醇反应的生物标志物。材料与方法：构建6个组织微阵列（tma），包括14个结肠粘膜、78个息肉和202个crc。免疫组织化学检测TUBB3表达，评分为阴性、局灶性和阳性。在HCT116细胞系中，用siRNA沉默TUBB3的表达。在tubb3沉默和对照的HCT116细胞株中评估紫杉醇毒性。结果：非肿瘤性结肠黏膜TUBB3表达为阴性，部分结肠腺瘤和crc表达TUBB3，表达水平从局灶性到弥漫性不等。表达TUBB3的crc往往预后较差，而TUBB3的沉默使细胞对紫杉醇敏感。结论：TUBB3在结直肠肿瘤亚组中表达。抑制TUBB3可能使肿瘤细胞对紫杉烷敏感。
Background/Aim: The challenges of cololorectal cancer (CRC) management include prediction of outcome and drug response or chemoresistance. This study aimed at examining whether beta III-tubulin (TUBB3), present in various types of normal tissues and cancer, is a biomarker for the response of colorectal neoplasms to paclitaxel. Materials and Methods: Six tissue microarrays (TMAs) including 14 colon mucosa, 78 polyps and 202 CRCs were constructed. Assessment of TUBB3 expression was performed by immunohistochemistry, and it was scored as negative, focal and positive. In the HCT116 cell line, TUBB3 expression was silenced with siRNA. Paclitaxel toxicity was evaluated in TUBB3-silenced and control HCT116 cell lines. Results: The non-neoplastic colon mucosa was negative for TUBB3, while some of colon adenomas and CRCs expressed TUBB3 in various levels from focal to diffuse. TUBB3-expressing CRCs tended to have poor prognosis and silencing of TUBB3 sensitized the cells to paclitaxel. Conclusion: TUBB3 was expressed in a subgroup of colorectal neoplasms. Suppression of TUBB3 potentialy sensitizes neoplastic cells to taxanes.