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GOLPH3 predicts survival of colorectal cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy

Authors :
Zhendan Yao
Bin Dong
Beihai Jiang
Jiafu Ji
Ming Cui
Lei Chen
Hong Yang
Nan Zhang
Jiadi Xing
Zaozao Wang
Chenghai Zhang
Yiyuan Ma
Xiangqian Su
Maoxing Liu
Jiabo Di
Source :
Journal of Translational Medicine
Publication Year :
2014
Publisher :
Springer Science and Business Media LLC, 2014.

Abstract

Background Golgi phosphoprotein 3 (GOLPH3) has been validated as a potent oncogene involved in the progression of many types of solid tumors, and its overexpression is associated with poor clinical outcome in many cancers. However, it is still unknown the association of GOLPH3 expression with the prognosis of colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy. Methods The expression of GOLPH3 was determined by qRT-PCR and immunohistochemistry in colorectal tissues from CRC patients treated with 5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5-FU sensitivity were examined in CRC cell lines. Results GOLPH3 expression was elevated in CRC tissues compared with matched adjacent noncancerous tissues. Kaplan-Meier survival curves indicated that high GOLPH3 expression was significantly associated with prolonged disease-free survival (DFS, P = 0.002) and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was an independent prognostic factor for DFS in CRC patients treated with 5-FU-based chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA-mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced apoptosis. Conclusions Our results suggest that GOLPH3 is associated with prognosis in CRC patients treated with postoperative 5-FU-based adjuvant chemotherapy, and may serve as a potential indicator to predict 5-FU chemosensitivity.

Details

ISSN :
14795876
Volume :
12
Database :
OpenAIRE
Journal :
Journal of Translational Medicine
Accession number :
edsair.doi.dedup.....b605851ff1fd63f6900e5b23898b1e00
Full Text :
https://doi.org/10.1186/1479-5876-12-15