NAP1L1 is a prognostic biomarker and contribute to doxorubicin chemotherapy resistance in human hepatocellular carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is one of the most fatal cancers, and its molecular basis needs to be delineated to identify biomarkers for its potential treatment. The purpose of this study was to identify a novel gene, nucleosome assembly proteins 1-like 1 protein (NAP1L1), associated with aggressive phenotypes of HCC. Methods Immunohistochemical staining was used to detect NAP1L1 protein expression in HCC tissues. The prognostic value of NAP1L1 expression was determined using Kaplan-Meier analysis and the Cox proportional hazards model. CCK-8 and apoptosis assays were used to detect the chemosensitivity in vitro. Xenograft tumor models were used to evaluate tumor cell proliferation and chemosensitivity in vivo. Results NAP1L1 expression was significantly upregulated in tumor tissues as compared to adjacent non-tumor tissues. High NAP1L1 expression in HCC tissues was associated with aggressive clinicopathologic features, such as serum AFP levels, tumor size and tumor number. Patients with high NAP1L1 expression had poor overall survival in our cohort and in the extra-validation cohort analyzed by TCGA microarray dataset and was further identified as an independent prognostic factor in HCC patients treated with radical resection. Both in vitro and in vivo assays showed that NAP1L1 promoted HCC cell proliferation and contribute to chemotherapy resistance. Further analyses found that some certain stemness associated genes were decreased concurrently with NAP1L1 down-regulation in HCC cell lines. Conclusions Our findings support that NAP1L1 is a prognostic biomarker and may contribute to chemotherapy resistance in human hepatocellular carcinoma.