title: Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer.
abstract: BACKGROUND
  Human replication factor C4 (RFC4) is involved in DNA replication as a clamp loader and is aberrantly regulated across a range of cancers. The current study aimed to investigate the function of RFC4 in colorectal cancer (CRC).
  
  
  METHODS
  The mRNA levels of RFC4 were assessed in 30 paired primary CRC tissues and matched normal colonic tissues by quantitative PCR. The protein expression levels of RFC4 were evaluated by western blotting (n = 16) and immunohistochemistry (IHC; n = 49), respectively. Clinicopathological features and survival data were correlated with the expression of RFC4 by IHC analysis in a tissue microarray comprising 331 surgically resected CRC. The impact of RFC4 on cell proliferation and the cell cycle was assessed using CRC cell lines.
  
  
  RESULTS
  RFC4 expression was significantly increased in CRC specimens as compared to adjacent normal colonic tissues (P <0.05). High levels of RFC4, determined on a tissue microarray, were significantly associated with differentiation, an advanced stage by the Tumor-Node-Metastasis (TNM) staging system, and a poor prognosis, as compared to low levels of expression (P <0.05). However, in multivariate analysis, RFC4 was not an independent predictor of poor survival for CRC. In vitro studies, the loss of RFC4 suppressed CRC cell proliferation and induced S-phase cell cycle arrest.
  
  
  CONCLUSIONS
  RFC4 is frequently overexpressed in CRC, and is associated with tumor progression and worse survival outcome. This might be attributed to the regulation of CRC cell proliferation and cell cycle arrest by RFC4.
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. xxj007@126.com.|Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. xxj007@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. fanglekun@hotmail.com.|Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. fanglekun@hotmail.com.|Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. fanglekun@hotmail.com.
authors.forename: Lekun
authors.initials: L
authors.lastname: Fang
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. luoyx25@mail.sysu.edu.cn.|Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. luoyx25@mail.sysu.edu.cn.|Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. luoyx25@mail.sysu.edu.cn.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. yzlhlj7068@163.com.|Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. yzlhlj7068@163.com.
authors.forename: Zuli
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. 13580306861@163.com.|Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. 13580306861@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshang Er Rd., Guangzhou, 510080, Guangdong, China. cuiji168@163.com.
authors.forename: Ji
authors.initials: J
authors.lastname: Cui
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. 13924073322@139.com.|Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. 13924073322@139.com.|Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. 13924073322@139.com.
authors.forename: Meijin
authors.initials: M
authors.lastname: Huang
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. yzh17@msn.com.|Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. yzh17@msn.com.
authors.forename: Zihuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. huangyan9229@yahoo.com.cn.|Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. huangyan9229@yahoo.com.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. juanjuanfan@163.com.|Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. juanjuanfan@163.com.
authors.forename: Xinjuan
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. angelwhs@sohu.com.|Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. angelwhs@sohu.com.
authors.forename: Huashe
authors.initials: H
authors.lastname: Wang
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. leiwangyinghu@yahoo.com.cn.|Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. leiwangyinghu@yahoo.com.cn.|Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. leiwangyinghu@yahoo.com.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. pengjunsheng@tom.com.|Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. pengjunsheng@tom.com.
authors.forename: Junsheng
authors.initials: J
authors.lastname: Peng
authors.affiliation: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. wangjply@yahoo.com.|Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. wangjply@yahoo.com.|Guangdong Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Er Heng Rd., Guangzhou, 510655, Guangdong, China. wangjply@yahoo.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051818:Replication Protein C / Q000378:metabolism*
chemical_list: C497563:RFC4 protein, human; D051818:Replication Protein C