Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, China.
Lab Invest. 2013 Dec;93(12):1276-87. doi: 10.1038/labinvest.2013.124. Epub 2013 Oct 21.
The KIAA0101 protein is overexpressed in various human cancers, including esophageal cancer (EC). This study assessed the association of KIAA0101 protein with prognosis and resistance to chemotherapy in EC patients and then explored the role of KIAA0101 in EC cells in vitro. A total of 228 EC patients participated in the study. Tissue samples were collected for immunohistochemical analysis of KIAA0101 expression in tumor and normal tissues for association with clinicopathological and survival data. KIAA0101 cDNA or shRNA were transfected into EC cells for assessment of tumor cell viability, sensitivity to cisplatin treatment, and gene expression. Array-based comparative genomic hybridization (aCGH) was used to detect the changed copy-number alterations in cell lines expressing different levels of KIAA0101. Expression of KIAA0101 protein was upregulated in EC tissues, which was associated with pTNM stage, resistance to chemotherapy, tumor recurrence, and poor survival of EC patients. In vitro experiments showed that expression of KIAA0101 enhanced cell proliferation and upregulated cyclins A and B expression, leading to a reduced G1 phase of the cell cycle. KIAA0101 also induced resistance of EC Eca-109 and TE-1 cell lines to cisplatin treatment through a decrease in apoptosis. The aCGH data showed that levels of KIAA0101 expression altered chromosome stability, affecting genes that are associated with cancer progression. In conclusion, upregulated KIAA0101 expression is associated with EC progression, resistance to chemotherapy, and poor survival of the patients.
KIAA0101 蛋白在多种人类癌症中过表达，包括食管癌（EC）。本研究评估了 KIAA0101 蛋白与 EC 患者预后和化疗耐药的相关性，然后探讨了 KIAA0101 在 EC 细胞中的作用。共有 228 名 EC 患者参与了这项研究。收集组织样本，通过免疫组织化学分析肿瘤和正常组织中 KIAA0101 的表达，与临床病理和生存数据相关联。将 KIAA0101 cDNA 或 shRNA 转染到 EC 细胞中，评估肿瘤细胞活力、对顺铂治疗的敏感性以及基因表达。基于阵列的比较基因组杂交（aCGH）用于检测表达不同水平 KIAA0101 的细胞系中改变的拷贝数改变。KIAA0101 蛋白的表达在 EC 组织中上调，与 pTNM 分期、化疗耐药、肿瘤复发和 EC 患者的不良生存相关。体外实验表明，KIAA0101 的表达增强了细胞增殖，并上调了细胞周期蛋白 A 和 B 的表达，导致细胞周期的 G1 期减少。KIAA0101 还通过减少细胞凋亡，诱导 EC Eca-109 和 TE-1 细胞系对顺铂治疗的耐药性。aCGH 数据显示，KIAA0101 表达水平改变了染色体稳定性，影响了与癌症进展相关的基因。总之，上调的 KIAA0101 表达与 EC 进展、化疗耐药和患者不良生存相关。
