title: Overexpression of CHKA contributes to tumor progression and metastasis and predicts poor prognosis in colorectal carcinoma.
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.
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China.|Department of Gastrointestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ruo-Yu
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Clinical Laboratory, 150th Hospital of PLA, Luoyang, China.
authors.forename: Guang-Zhen
authors.initials: GZ
authors.lastname: Yang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Xu
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China.
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Zhai
authors.affiliation: Anal-Colorectal Surgery Institute, 150th Hospital of PLA, Luoyang, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
authors.affiliation: Department of Gastrointestine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002797:Choline Kinase / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D034622:RNA Interference; D055815:Young Adult
chemical_list: C517212:CHKA protein, human; D002797:Choline Kinase
keywords: CHKA; biomarker; colorectal carcinoma; prognosis; progression