GOLPH3 predicts survival of colorectal cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.
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.
Zaozao
Z
Wang
Beihai
B
Jiang
Lei
L
Chen
Jiabo
J
Di
Ming
M
Cui
Maoxing
M
Liu
Yiyuan
Y
Ma
Hong
H
Yang
Jiadi
J
Xing
Chenghai
C
Zhang
Zhendan
Z
Yao
Nan
N
Zhang
Bin
B
Dong
Jiafu
J
Ji
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Minimally Invasive Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, 100142 Beijing, China. suxiangqian@bjmu.edu.cn.
Xiangqian
X
Su
D000368:Aged; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism
C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D011065:Poly(ADP-ribose) Polymerases; D005472:Fluorouracil