Oncotarget

Research Papers:

Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma

Liang Hu, Ruo-Yu Wang, Jian Cai, Dan Feng, Guang-Zhen Yang, Qing-Guo Xu, Yan-Xia Zhai, Yu Zhang, Wei-Ping Zhou and Qing-Ping Cai _

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Oncotarget. 2016; 7:66660-66678. https://doi.org/10.18632/oncotarget.11433

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Abstract

Liang Hu1,6,*, Ruo-Yu Wang2,*, Jian Cai3,*, Dan Feng4,*, Guang-Zhen Yang5, Qing-Guo Xu2, Yan-Xia Zhai1, Yu Zhang1, Wei-Ping Zhou2, Qing-Ping Cai6

1Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China

2The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China

3Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

4Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China

5Department of Clinical Laboratory, 150th Hospital of PLA, Luoyang, China

6Department of Gastrointestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China

*These authors contributed equally to this work

Correspondence to:

Liang Hu, email: lianghudoc@163.com

Qing-Ping Cai, email: caiqingpingwcwk@163.com

Keywords: CHKA, colorectal carcinoma, progression, prognosis, biomarker

Received: January 06, 2016     Accepted: August 13, 2016     Published: August 20, 2016

ABSTRACT

Aberrant expression of choline kinase alpha (CHKA) has been reported in a variety of human malignancies including colorectal carcinoma (CRC). However, the role of CHKA in the progression and prognosis of CRC remains unknown. In this study, we found that CHKA was frequently upregulated in CRC clinical samples and CRC-derived cell lines and was significantly correlated with lymph node metastasis (p = 0.028), TNM stage (p = 0.009), disease recurrence (p = 0.004) and death (p < 0.001). Survival analyses indicated that patients with higher CHKA expression had a significantly shorter disease-free survival (DFS) and disease-specific survival (DSS) than those with lower CHKA expression. Multivariate analyses confirmed that increased CHKA expression was an independent unfavorable prognostic factor for CRC patients. In addition, combination of CHKA with TNM stage was a more powerful predictor of poor prognosis than either parameter alone. Functional study demonstrated that knockdown of CHKA expression profoundly suppressed the growth and metastasis of CRC cells both in vitro and in vivo. Mechanistic investigation revealed that EGFR/PI3K/AKT pathway was essential for mediating CHKA function. In conclusion, our results provide the first evidence that CHKA contributes to tumor progression and metastasis and may serve as a novel prognostic biomarker and potential therapeutic target in CRC.


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