Research Papers:

Downregulation of phosphorylated MKK4 is associated with a poor prognosis in colorectal cancer patients

Pu-Ning Wang, Jun Huang, Ying-Hua Duan, Jia-Min Zhou, Pin-Zhu Huang, Xin-Juan Fan, Yan Huang, Lei Wang, Huan-Liang Liu, Jian-Ping Wang and Mei-Jin Huang _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:34352-34361. https://doi.org/10.18632/oncotarget.16128

Metrics: PDF 1549 views  |   HTML 2200 views  |   ?  


Pu-Ning Wang1,*, Jun Huang1,*, Ying-Hua Duan2,*, Jia-Min Zhou1, Pin-Zhu Huang1, Xin-Juan Fan3, Yan Huang3, Lei Wang1, Huan-Liang Liu4, Jian-Ping Wang1, Mei-Jin Huang1

1Department of Colorectal Surgery, The 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

2Department of Traditional Chinese Medicine, The 1st Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

3Department of Pathology, The 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

4Gastrointestinal Diseases Research Institute of Guangdong Province, The 6th Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

*These authors contributed equally to this work

Correspondence to:

Mei-Jin Huang, email: [email protected]

Keywords: phosphorylated mitogen-activated protein kinase kinase 4, colorectal cancer, metastasis

Received: September 20, 2016     Accepted: February 01, 2017     Published: March 11, 2017


Mitogen-activated protein kinase kinase 4 (MKK4) is a key mediator of Jun N-terminal kinase signaling and influences malignant metastasis. Here, we used immunohistochemistry to assess phosphorylated MMK4 (pMKK4) levels and examine their association with the clinicopathological features of a pilot set of patient samples consisting of normal colonic mucosa (NCM), colorectal adenoma (CA), and colorectal cancer (CRC) tissues. pMKK4 levels were also assessed in a validation set of CRC cases with accompanying follow-up data to confirm their clinicopathological and prognostic significance. pMKK4 levels, which were high in 79.17% of NCM samples, were downregulated in 33.33% of CA and 63.54% of CRC samples. pMKK4 downregulation was associated with metastasis, especially to the liver. In the validation set, pMKK4 downregulation was associated with increases in invasive depth, lymph node metastasis, distant metastasis, and TNM stage. Univariate analysis indicated that pMKK4 score, tumor differentiation, and TNM stage were correlated with disease-free survival and overall survival. Multivariate analysis indicated that decreased pMKK4 expression was an independent risk factor for disease-free survival in CRC patients. These results suggest that CRC patients with low pMKK4 immunochemistry scores should be monitored carefully for early detection of possible recurrences, especially liver metastasis.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 16128