title: Radiofrequency ablation-increased CXCL10 is associated with earlier recurrence of hepatocellular carcinoma by promoting stemness.
abstract: Radiofrequency ablation (RFA) represents a valuable choice in hepatocellular carcinoma (HCC); however, local recurrence of HCC is common after RFA. Here, 20 primary HCC patients treated by RFA were enrolled. Before (termed 0d) and after RFA treatment for 1 and 7 days (termed 1d and 7d, respectively), plasma and noncancerous tissue were collected. ELISA assay showed that plasma C-X-C motif chemokine 10 (CXCL10) was increased in ten patients (type I patients) but decreased in the other 10 patients (type II patients). The mean interval for HCC recurrence in type I patients was less than the mean interval in type II patients. Interestingly, a significant negative correlation between interval for HCC recurrence and fold change of plasma CXCL10 (1d/0d or 7d/0d) was identified, suggesting that RFA-induced CXCL10 is associated with earlier HCC recurrence. Immunofluorescence assay showed that the receptor of CXCL10, chemokine (C-X-C motif) receptor 3 (CXCR3), was significantly increased in type I, but not type II, patients after RFA. In vitro assay demonstrated that CXCL10 stimulus increased the rate of CD133(+) cancer stem cells (CSCs) in HepG2 cells by binding to CXCR3 and then inducing c-Myc expression. Many studies have reported that induction of CD133(+) CSCs contributes to HCC recurrence. Thus, CXCL10-increased CD133(+) CSCs by activating CXCR3/c-Myc pathway might accelerate HCC recurrence after RFA. These data might have potential implications for HCC therapy.
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.|Beijing Institute of Hepatology, Beijing, 100069, China.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.|Beijing Institute of Hepatology, Beijing, 100069, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.
authors.forename: Meijun
authors.initials: M
authors.lastname: Hao
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.|Beijing Institute of Hepatology, Beijing, 100069, China.
authors.forename: Rongling
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.|Beijing Institute of Hepatology, Beijing, 100069, China.
authors.forename: Chunmiao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.|Beijing Institute of Hepatology, Beijing, 100069, China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.|Beijing Institute of Hepatology, Beijing, 100069, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China.|Beijing Institute of Hepatology, Beijing, 100069, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China. jiashengzheng@outlook.com.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Beijing You'an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, People's Republic of China. dexichen@ccmu.edu.cn.|Beijing Institute of Hepatology, Beijing, 100069, China. dexichen@ccmu.edu.cn.
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000378:metabolism / Q000601:surgery*; D017115:Catheter Ablation / Q000379:methods*; D054357:Chemokine CXCL10 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000097:blood / Q000378:metabolism / Q000601:surgery*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000071916:AC133 Antigen; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D054367:Receptors, CXCR3; D011994:Recombinant Proteins
keywords: CXCL10; CXCR3; Cancer stem cell; Hepatocellular carcinoma; Radiofrequency ablation