Guan Chengqi, Liu Zhaoxiu, Lu Cuihua, Xiao Mingbing, Shi Hui, Ni Runzhou, Bian Zhaolian
Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
J Cell Biochem. 2019 Jul;120(7):11726-11737. doi: 10.1002/jcb.28452. Epub 2019 Feb 21.
The microtubule binding protein, nucleolar spindle-associated protein 1 (NUSAP1), has a crucial function in mitosis and its expression is closely associated with carcinogenesis. Herein, we aimed to determine the function of NUSAP1 in the development of human esophageal squamous cell carcinoma (ESCC), and the association of NUSAP1 expression with ESCC. Immunohistochemical staining of ESCC tissue sections indicated that NUSAP1 was expressed to a higher degree in tumor tissues than in adjacent nontumor tissues. NUSAP1 levels were relevant closely to histological differentiation (P = 0.049). Overall survival was longer in patients with lower NUSAP1 levels ( P < 0.001). NUSAP1 expression ( P = 0.002), histological differentiation ( P < 0.001), tumor depth ( P = 0.045), lymph node metastases ( P < 0.001), and tumor-node-metastasis staging ( P = 0.008) were greatly associated with overall survival using univariate analysis. Multivariate analysis suggested that histological differentiation ( P = 0.014) and NUSAP1 expression ( P = 0.026) could be independent prognostic markers for ESCC. Additionally, the biological behavior of ESCC cells was investigated in vitro and in vivo. Suppression of NUSAP1 inhibited cellular proliferation and invasion, and induced cell cycle arrest and apoptosis in vitro. More importantly, knockdown of NUSAP1 led to inhibition of tumor formation in nude mice. These findings indicated that NUSAP1 is a potential prognostic biomarker in ESCC, and is an ESCC oncogene. Thus, NUSAP1 could represent a therapeutic target for ESCC.
微管结合蛋白核仁纺锤体相关蛋白1（NUSAP1）在有丝分裂中起关键作用，其表达与肿瘤发生密切相关。在此，我们旨在确定NUSAP1在人类食管鳞状细胞癌（ESCC）发生发展中的作用，以及NUSAP1表达与ESCC的关联。ESCC组织切片的免疫组化染色表明，NUSAP1在肿瘤组织中的表达程度高于相邻的非肿瘤组织。NUSAP1水平与组织学分化密切相关（P = 0.049）。NUSAP1水平较低的患者总生存期更长（P < 0.001）。单因素分析显示，NUSAP1表达（P = 0.002）、组织学分化（P < 0.001）、肿瘤深度（P = 0.045）、淋巴结转移（P < 0.001）和肿瘤-淋巴结-转移分期（P = 0.008）与总生存期密切相关。多因素分析表明，组织学分化（P = 0.014）和NUSAP1表达（P = 0.026）可能是ESCC的独立预后标志物。此外，还在体外和体内研究了ESCC细胞的生物学行为。抑制NUSAP1可抑制细胞增殖和侵袭，并在体外诱导细胞周期停滞和凋亡。更重要的是，敲低NUSAP1导致裸鼠肿瘤形成受到抑制。这些发现表明，NUSAP1是ESCC潜在的预后生物标志物，是一种ESCC癌基因。因此，NUSAP1可能是ESCC的治疗靶点。
