Karyopherin α-2 is a reliable marker for identification of patients with high-risk stage II colorectal cancer

被引:16
作者
Jeong, Dongjun [1 ,2 ]
Kim, Hyeongjoo [2 ]
Ban, Seona [2 ]
Oh, Seunghyun [2 ]
Ji, Sanghee [2 ]
Kim, Doyeon [2 ]
Ahn, Tae Sung [3 ]
Kim, Han Jo [4 ]
Bae, Sang Byung [4 ]
Kwon, Hyog Young [1 ]
Im, Jungkyun [5 ]
Lee, Moon Soo [3 ]
Cho, Hyun Deuk [1 ]
Kim, Chang-Jin [1 ]
Baek, Moo-Jun [3 ]
机构
[1] Soonchunhyang Univ, Dept Pathol, Coll Med, 31 Soonchunhyang 6 Gil, Cheonan 31151, Chungcheongnam, South Korea
[2] Soonchunhyang Univ, Soonchunhyang Med Sci Res Inst, Coll Med, 31 Soonchunhyang 6 Gil, Cheonan 31151, Chungcheongnam, South Korea
[3] Soonchunhyang Univ, Dept Surg, Coll Med, 31 Soonchunhyang 6 Gil, Cheonan 330723, Chungcheongnam, South Korea
[4] Soonchunhyang Univ, Dept Oncol, Coll Med, Cheonan 31151, Chungcheongnam, South Korea
[5] Soonchunhyang Univ, Dept Nanochem Engn, 22 Soonchunhyangro, Asan 31536, Chungcheongnam, South Korea
基金
新加坡国家研究基金会;
关键词
Colorectal cancer; KPNA2; Prognostic marker; CRC stage II; NUCLEAR-TRANSPORT; COLON-CANCER; SURVIVAL; CARCINOMA; OVEREXPRESSION; TRANSFORMATION; PROLIFERATION; FLUOROURACIL; METASTASIS; EXPRESSION;
D O I
10.1007/s00432-017-2512-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Adjuvant chemotherapy (AC) is frequently considered in patients with high-risk stage II colorectal cancer (CRC). Among patients with stage II CRC who do not receive AC because they are not considered to be at high risk, 20-25% will develop recurrence and die from the disease. Elevated levels of KPNA2 have been observed in various cancers, and overexpression of KPNA2 is related to CRC progression. We examined the expression of KPNA2 using 293 CRC tissues, including 118 with stage II CRC, and investigated the applicability of KPNA2 as a biomarker to predict high-risk stage II CRC. Moreover, we further investigated the role of KPNA2 as an oncogene in CRC carcinogenesis using in vitro functional studies. High KPNA2 expression was associated with vascular (p = 0.027) and lymphatic invasion (p = 0.009) in patients with stage II CRC. On multivariate analysis, high KPNA2 expression (HR 3.174, 95% CI 2.060-4.889; p < 0.001) was independently associated with survival in patients with CRC. The overall survival rate in patients with high KPNA2 expression was higher than that in patients with low KPNA2 expression in CRC (p < 0.001), even in patients with stage II CRC (p = 0.001). Additionally, KPNA2 was associated with tumorigenesis and cancer progression in CRC cells; high KPNA2 expression was associated with increased cell proliferation (p < 0.05), migration (p = 0.03), invasion (p = 0.001), and semisolid agar colony formation (p < 0.001). KPNA2 expression is useful for identification of patients with high-risk stage II CRC who could benefit from AC and that KPNA2 may also be a promising therapeutic target.
引用
收藏
页码:2493 / 2503
页数:11
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