Karyopherin alpha 2 is a novel prognostic marker and a potential therapeutic target for colon cancer.
Karyopherin alpha 2 is a novel prognostic marker and a potential therapeutic target for colon cancer.
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Karyopherin α 2 是一种新型预后标志物，也是结肠癌的潜在治疗靶点
DOI：
10.1186/s13046-015-0261-3
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Peng Z
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhang M;Yu F;Lu S;Sun H;Tang H;Peng Z
研究背景KPNA 2（Karyopherin alpha 2）是核转运蛋白家族的成员之一，在肿瘤的发生发展中起重要作用。然而，它在结肠癌中的作用却很难描述。我们试图阐明其异常表达的临床意义在人类结肠肿瘤samples.MethodsWe评估KPNA 2 mRNA和蛋白表达的实时聚合酶链反应和蛋白质印迹法在40原发性结肠癌组织和配对的相邻正常结肠粘膜标本。采用免疫组化方法分析了195例结肠癌患者的肿瘤组织、正常组织和淋巴结转移组织中KPNA 2蛋白的表达。采用CCK-8法检测KPNA 2基因敲减对人结肠癌细胞成癌潜能、克隆形成、细胞迁移和裸鼠成瘤能力的影响。KPNA 2阳性肿瘤患者与美国癌症联合委员会（AJCC）分期（p= 0.01）、T分类（p= 0.018）、区域淋巴结转移（p= 0.025）、远处转移（p= 0.014）和分化程度（p= 0.001）显著相关。KPNA 2被证明是结肠癌患者无病生存期（HR 1.681; 95% CI：1.170-2.416;p= 0.005）和总生存期（HR 2.770; 95% CI：1.314-5.837;p= 0.007）的独立预后指标。结论KPNA 2在大肠癌的发生发展中起重要作用，可能是大肠癌的一个新的预后指标和潜在的治疗靶点。
BackgroundKaryopherin alpha 2 (KPNA2), a member of the karyopherin family, plays a vital role in carcinogenesis. Yet its role in colon cancer is poorly characterized. We sought to clarify the clinical significance of its dysregulated expression in human colon tumor specimens.MethodsWe evaluated KPNA2 mRNA and protein expression by real-time polymerase chain reaction and Western blotting in 40 primary colon cancer tissues and paired adjacent normal colon mucosa specimens. KPNA2 protein expression in colon tissue microarray of tumor and normal tissue specimens and lymph node metastasis specimens obtained from 195 colon cancer patients were analyzed immunohistochemically. The effect of KPNA2 knockdown on carcinogenesis potential of human colon cancer cells was determined using Cell Counting Kit-8 (CCK8), colony formation, cell migration, and tumorigenesis in nude mice.ResultsKPNA2 was expressed at higher levels in colon tumors and lymph node metastasis specimens than in normal tissues. Patients with KPNA2-positive tumors were significantly correlated with the American Joint Committee on Cancer (AJCC) stage (p= 0.01), T-classification (p= 0.018), regional lymph node metastasis (p= 0.025), distant metastasis (p= 0.014), and differentiated degree (p= 0.001). KPNA2 was shown to be an independent prognostic indicator of disease-free survival (HR 1.681; 95 % CI: 1.170–2.416;p= 0.005) and overall survival (HR 2.770; 95 % CI: 1.314–5.837;p= 0.007) for patients with colon cancer. Knockdown of KPNA2 expression inhibited colon cancer cell proliferation, colony formation, and migration.ConclusionKPNA2 might play an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for colorectal cancer.