Dongjun Jeong1,2, Hyeongjoo Kim2, Seona Ban2, Seunghyun Oh2, Sanghee Ji2, Doyeon Kim2, Tae Sung Ahn3, Han Jo Kim4, Sang Byung Bae4, Hyog Young Kwon1, Jungkyun Im5, Moon Soo Lee3, Hyun Deuk Cho1, Chang-Jin Kim1, Moo-Jun Baek6. 1. Department of Pathology, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 31151, Republic of Korea. 2. Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 31151, Republic of Korea. 3. Department of Surgery, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 330-723, Republic of Korea. 4. Department of Oncology, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 31151, Republic of Korea. 5. Department of Nanochemical Engineering, Soonchunhyang University, 22 Soonchunhyangro, Shinchang-myeon, Asansi, Chungcheongnam-do, 31536, Republic of Korea. 6. Department of Surgery, College of Medicine, Soonchunhyang University, 31 Soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 330-723, Republic of Korea. ssurge@sch.ac.kr.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: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.
Authors: Pauline J van der Watt; Christopher P Maske; Denver T Hendricks; M Iqbal Parker; Lynette Denny; Dhirendra Govender; Michael J Birrer; Virna D Leaner Journal: Int J Cancer Date: 2009-04-15 Impact factor: 7.396
Authors: M A Merok; T Ahlquist; E C Røyrvik; K F Tufteland; M Hektoen; O H Sjo; T Mala; A Svindland; R A Lothe; A Nesbakken Journal: Ann Oncol Date: 2012-12-12 Impact factor: 32.976