J Cancer 2017; 8(5):801-808. doi:10.7150/jca.17640
Protein Regulator of Cytokinesis PRC1 Confers Chemoresistance and Predicts an Unfavorable Postoperative Survival of Hepatocellular Carcinoma Patients
1. Department of Gastroenterology, Qingdao Municipal Hospital, Medical College, Qingdao University, Qingdao, Shandong, China;
2. Department of Gastroenterology, Rizhao People's Hospital, Rizhao, Shandong, China;
3. Department of Digestive Medicine, Rizhao Traditional Chinese Medicine Hospital, Wanghai Road, Rizhao, Shandong, China;
4. Department of Gynaecology and Obstetrics, Rizhao Maternal and Child Health Hospital, Rizhao, Shandong, China;
5. Endoscope Center, Rizhao Traditional Chinese Medicine Hospital, Wanghai Road, Rizhao, Shandong, China;
6. Department of Pathology, Rizhao People's Hospital, Rizhao, Shandong, China;
7. Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China;
8. Department of Cardiovascular Surgery of the First Affiliated Hospital& Institute for Cardiovascular Science, Soochow University, Suzhou, Jiangsu, China.
*These authors contributed equally to this work.
Background: PRC1, a microtubules(MTs)-associated protein, is essential in the mitosis and cell cycle regulation. It has been recently linked to chemoresistance and tumorigenesis. The current study sought to explore the role of PRC1 on chemoresistance and postoperative prognosis of hepatocellular carcinoma(HCC).
Methods: PRC1 was transfected into HCC cells to detect its effects of chemoresistance to 5-fluorouracil in vitro and in vivo. This study also investigated the impact of PRC1 on 5-FU-induced G2/M phase arrest and the potential molecular mechanism. Surgical specimens from HCC patients were examined immunohistochemically for PRC1 expression.
Results: Ectopic expression of PRC1 significantly increased the chemoresistance, promoted the tumor growth and abrogated 5-FU-induced G2/M phase arrest via p21/p27-pRBs pathway. In clinical specimens, high expression of PRC1(immunostaining score≥3) in HCC cells predicted an unfavorable postoperative survival of HCC patients(P=0.019), especially for whom received postoperative chemotherapy(P=0.002). In multivariate Cox analyses, high PRC1 expression significantly predicted an unfavorable postoperative prognosis, not dependent of TNM stage.
Conclusion: High PRC1 expression in HCC cells increased chemoresistance, attenuated 5-FU-induced apoptosis, abrogated 5-FU-induced G2/M phase arrest, and predicts an unfavorable survival, especially for the patients who received chemotherapy. PRC1 might be a novel prognostic and predictive marker and therapeutic target for HCC patients.
Keywords: PRC1, chemoresistance, postoperative, survival, hepatocellular carcinoma.
Wang Y, Shi F, Xing GH, Xie P, Zhao N, Yin YF, Sun SY, He J, Wang Y, Xuan SY. Protein Regulator of Cytokinesis PRC1 Confers Chemoresistance and Predicts an Unfavorable Postoperative Survival of Hepatocellular Carcinoma Patients. J Cancer 2017; 8(5):801-808. doi:10.7150/jca.17640. Available from http://www.jcancer.org/v08p0801.htm