Differential expression of DUSP2 in left- and right-sided colon cancer is associated with poor prognosis in colorectal cancer

被引:15
作者
Dong, Wenjie [1 ]
Li, Na [1 ]
Pei, Xiufeng [2 ]
Wu, Xinai [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Internal Med Oncol, 1 East Jianshe Rd, Zhengzhou 450052, Henan, Peoples R China
[2] Tumor Hosp Baotou, Dept Internal Med Oncol, Baotou 014030, Inner Mongolia, Peoples R China
基金
中国国家自然科学基金;
关键词
dual-specificity phosphatase-2; colorectal cancer; prognosis; cetuximab; DUAL-SPECIFICITY PHOSPHATASE-2; GROWTH-FACTOR; RESISTANCE; APOPTOSIS; CETUXIMAB; LOCATION; BENEFIT; CELLS; TUMOR;
D O I
10.3892/ol.2018.7881
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Dual-specificity phosphatase-2 (DUSP2), a negative regulator of extracellular-regulated kinase activity, has been identified as an important kinase with emerging roles in cancer. However, the clinical significance of DUSP2 in colorectal cancer (CRC) remains to be fully elucidated. In the present study, the expression of DUSP2 was investigated using immunohistochemistry in 96 patients with CRC. Cell viability was estimated using a cell counting kit-8 assay, and cell apoptosis by flow cytometry. The relationship between DUSP2 expression and patient characteristics, including overall survival, were studied retrospectively in these patients. It was found that DUSP2 was differentially expressed between left-sided colon carcinoma (LSCC) and right-sided colon carcinoma (RSCC). It was also found that decreased expression of DUSP2 was correlated with significantly shorter overall survival (P=0.001) and short distant-metastasis-free survival (P=0.002). In univariate comparisons, the decreased expression of DUSP2 was found to be an independent risk factor for poor survival rate (HR 3.55, CI 1.092-9.896; P=0.002). It was also found that the enforced overexpression of DUSP2 sensitized CRC cells to cetuximab. In conclusion, the findings demonstrated that DUSP2 was differentially expressed between RSCC and LSCC, and that the overexpression of DUSP2 increased the inhibitory effect of cetuximab in CRC, suggesting that DUSP2 may be a novel biomarker and therapeutic target in CRC therapy.
引用
收藏
页码:4207 / 4214
页数:8
相关论文
共 28 条
  • [1] The dual-specificity MAP kinase phosphatases: critical roles in development and cancer
    Bermudez, O.
    Pages, G.
    Gimond, C.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2010, 299 (02): : C189 - C202
  • [2] Overcoming cetuximab resistance in HNSCC: The role of AURKB and DUSP proteins
    Boeckx, Carolien
    de Beeck, Ken Op
    Wouters, An
    Deschoolmeester, Vanessa
    Limame, Ridha
    Zwaenepoel, Karen
    Specenier, Pol
    Pauwels, Patrick
    Vermorken, Jan B.
    Peeters, Marc
    Van Camp, Guy
    Baay, Marc
    Lardon, Filip
    [J]. CANCER LETTERS, 2014, 354 (02) : 365 - 377
  • [3] Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17
    Brule, S. Y.
    Jonker, D. J.
    Karapetis, C. S.
    O'Callaghan, C. J.
    Moore, M. J.
    Wong, R.
    Tebbutt, N. C.
    Underhill, Cr.
    Yip, D.
    Zalcberg, J. R.
    Tu, D.
    Goodwin, R. A.
    [J]. EUROPEAN JOURNAL OF CANCER, 2015, 51 (11) : 1405 - 1414
  • [4] EGFR-activating mutations, DNA copy number abundance of ErbB family, and prognosis in lung adenocarcinoma
    Chen, Hsuan-Yu
    Liu, Chia-Hsin
    Chang, Ya-Hsuan
    Yu, Sung-Liang
    Ho, Bing-Ching
    Hsu, Chung-Ping
    Yang, Tsung-Ying
    Chen, Kun-Chieh
    Hsu, Kuo-Hsuan
    Tseng, Jeng-Sen
    Hsia, Jiun-Yi
    Chuang, Cheng-Yen
    Chang, Chi-Sheng
    Li, Yu-Cheng
    Li, Ker-Chau
    Chang, Gee-Chen
    Yang, Pan-Chyr
    [J]. ONCOTARGET, 2016, 7 (08) : 9017 - 9025
  • [5] Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer
    Dienstmann, Rodrigo
    Vermeulen, Louis
    Guinney, Justin
    Kopetz, Scott
    Tejpar, Sabine
    Tabernero, Josep
    [J]. NATURE REVIEWS CANCER, 2017, 17 (02) : 79 - 92
  • [6] The PAC-1 dual specificity phosphatase predicts poor outcome in serous ovarian carcinoma
    Givant-Horwitz, V
    Davidson, B
    Goderstad, JM
    Nesland, JM
    Tropé, CG
    Reich, R
    [J]. GYNECOLOGIC ONCOLOGY, 2004, 93 (02) : 517 - 523
  • [7] The dual specificity phosphatase 2 gene is hypermethylated in human cancer and regulated by epigenetic mechanisms
    Haag, Tanja
    Richter, Antje M.
    Schneider, Martin B.
    Jimenez, Adriana P.
    Dammann, Reinhard H.
    [J]. BMC CANCER, 2016, 16
  • [8] Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthritis
    Hamamura, Kazunori
    Nishimura, Akinobu
    Chen, Andy
    Takigawa, Shinya
    Sudo, Akihiro
    Yokota, Hiroki
    [J]. CELLULAR SIGNALLING, 2015, 27 (04) : 828 - 835
  • [9] Hypoxia-Induced Downregulation of DUSP-2 Phosphatase Drives Colon Cancer Stemness
    Hou, Pei-Chi
    Li, Yo-Hua
    Lin, Shih-Chieh
    Lin, Shau-Chieh
    Lee, Jenq-Chang
    Lin, Bo-Wen
    Liou, Jing-Ping
    Chang, Jang-Yang
    Kuo, Ching-Chuan
    Liu, Yi-Min
    Sun, H. Sunny
    Tsai, Shaw-Jenq
    [J]. CANCER RESEARCH, 2017, 77 (16) : 4305 - 4316
  • [10] Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells
    Joo, Donghyun
    Woo, Jong Soo
    Cho, Kwang-Hyun
    Han, Seung Hyun
    Min, Tae Sun
    Yang, Deok-Chun
    Yun, Cheol-Heui
    [J]. BMB REPORTS, 2016, 49 (04) : 220 - 225