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

Abstract

// Liang Hu 1, 6, * , Ruo-Yu Wang 2, * , Jian Cai 3, * , Dan Feng 4, * , Guang-Zhen Yang 5 , Qing-Guo Xu 2 , Yan-Xia Zhai 1 , Yu Zhang 1 , Wei-Ping Zhou 2 , Qing-Ping Cai 6 1 Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China 2 The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 3 Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 4 Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China 5 Department of Clinical Laboratory, 150th Hospital of PLA, Luoyang, China 6 Department 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.