Jeong Dongjun, Kim Hyeongjoo, Ban Seona, Oh Seunghyun, Ji Sanghee, Kim Doyeon, Ahn Tae Sung, Kim Han Jo, Bae Sang Byung, Kwon Hyog Young, Im Jungkyun, Lee Moon Soo, Cho Hyun Deuk, Kim Chang-Jin, Baek Moo-Jun
Department of Pathology, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 31151, Republic of Korea.
Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 31151, Republic of Korea.
J Cancer Res Clin Oncol. 2017 Dec;143(12):2493-2503. doi: 10.1007/s00432-017-2512-5. Epub 2017 Sep 5.
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.
高危II期结直肠癌（CRC）患者常考虑辅助化疗（AC）。在因不被认为处于高危而未接受AC的II期CRC患者中，20 - 25%会出现复发并死于该疾病。在各种癌症中均观察到KPNA2水平升高，且KPNA2的过表达与CRC进展相关。
我们使用293例CRC组织（包括118例II期CRC组织）检测了KPNA2的表达，并研究了KPNA2作为预测高危II期CRC生物标志物的适用性。此外，我们通过体外功能研究进一步探究了KPNA2作为癌基因在CRC致癌过程中的作用。
II期CRC患者中，高KPNA2表达与血管侵犯（p = 0.027）和淋巴侵犯（p = 0.009）相关。多因素分析显示，高KPNA2表达（HR 3.174，95%CI 2.060 - 4.889；p < 0.001）与CRC患者的生存独立相关。CRC患者中，高KPNA2表达患者的总生存率高于低KPNA2表达患者（p < 0.001），即使在II期CRC患者中也是如此（p = 0.001）。此外，KPNA2与CRC细胞的肿瘤发生和癌症进展相关；高KPNA2表达与细胞增殖增加（p < 0.05）、迁移（p = 0.03）、侵袭（p = 0.001）和半固体琼脂集落形成增加（p < 0.001）相关。
KPNA2表达有助于识别可能从AC中获益的高危II期CRC患者，且KPNA2也可能是一个有前景的治疗靶点。
