Elsevier

Laboratory Investigation

Volume 93, Issue 12, December 2013, Pages 1276-1287
Laboratory Investigation

Article
Expression of KIAA0101 protein is associated with poor survival of esophageal cancer patients and resistance to cisplatin treatment in vitro

https://doi.org/10.1038/labinvest.2013.124Get rights and content
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Abstract

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.

chemotherapy
esophageal cancer
KIAA0101

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KIAA0101 is a protein involved in the regulation of DNA repair, cell cycle progression, and migration. Its elevated expression in esophageal cancer is associated with resistance to chemotherapy, recurrence, and poor survival. This paper shows that in esophageal cancer, KIAA0101 enhances cell proliferation, increases resistance to cisplatin treatment, and alters chromosome stability. These findings suggest KIAA0101 as a target for therapy.

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Yao Cheng and Kang Li: These authors contributed equally to this work.