PMID- 37351997
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20230630
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 43
IP  - 7
DP  - 2023 Jul
TI  - Tissue Expression and Prognostic Role of CXCL12 and CXCR4 in High-grade Serous 
      Ovarian Carcinoma.
PG  - 3331-3340
LID - 10.21873/anticanres.16509 [doi]
AB  - BACKGROUND/AIM: The complex of C-X-C motif chemokine receptor 4 (CXCR4) and its 
      ligand, C-X-C motif chemokine ligand 12 (CXCL12), plays an essential role in 
      cancer cell proliferation, invasion, and metastasis. These are emerging 
      therapeutic targets, and recent studies have reported that inhibition of 
      CXCL12-CXCR4 signaling pathway enhances the effects of immune checkpoint 
      inhibitors. Thus, we aimed to investigate tissue expression of CXCL12 and CXCR4 
      in high-grade serous ovarian carcinoma (HGSOC) and to determine their potential 
      as prognostic markers. PATIENTS AND METHODS: We used chemotherapy-naive, 
      formalin-fixed paraffin-embedded primary ovarian cancer tissues obtained from 
      patients with advanced-stage HGSOC at the time of primary cytoreductive surgery. 
      After histological reassessment, we constructed a tissue microarray and performed 
      immunohistochemical staining for CXCL12 and CXCR4. Thereafter, 
      clinicopathological characteristics and survival outcomes were compared between 
      the high- and low-expression groups. RESULTS: A total of 97 patients with FIGO 
      stage IIIC-IV HGSOC were included: 15 (15.5%), 66 (68.0%), and 13 (13.4%) 
      patients showed high expression of CXCL12, CXCR4, and both, respectively. The 
      expression level of each protein was not associated with germline BRCA1/2 
      mutational status, FIGO stage, or residual tumor after primary cytoreductive 
      surgery. In multivariate analysis adjusted for confounders, high CXCL12 
      expression was identified as an independent poor prognostic biomarker for 
      progression-free survival (adjusted hazards ratio, 1.990; 95% confidence 
      interval=1.090-3.633; p=0.025). However, CXCR4 expression was not associated with 
      patient survival outcomes. CONCLUSION: The CXCL12 expression level may represent 
      a prognostic biomarker for HGSOC. Proteins related to the CXCL12/CXCR4 complex 
      may serve as therapeutic targets in HGSOC treatment.
CI  - Copyright (c) 2023 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Lim, Hyunji
AU  - Lim H
AD  - Department of Obstetrics and Gynecology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Kim, Se Ik
AU  - Kim SI
AD  - Department of Obstetrics and Gynecology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Kim, Eun Na
AU  - Kim EN
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Lee, Maria
AU  - Lee M
AD  - Department of Obstetrics and Gynecology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Lee, Cheol
AU  - Lee C
AD  - Department of Pathology, Seoul National University College of Medicine, Seoul, 
      Republic of Korea.
FAU - Kim, Jae-Weon
AU  - Kim JW
AD  - Department of Obstetrics and Gynecology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea.
FAU - Chung, Hyun Hoon
AU  - Chung HH
AD  - Department of Obstetrics and Gynecology, Seoul National University College of 
      Medicine, Seoul, Republic of Korea; chhkmj1@snu.ac.kr.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Biomarkers)
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA1 protein, human)
RN  - 0 (BRCA2 Protein)
RN  - 0 (BRCA2 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Ligands)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Female
MH  - Humans
MH  - Biomarkers
MH  - BRCA1 Protein/metabolism
MH  - BRCA2 Protein
MH  - *Chemokine CXCL12/genetics/metabolism
MH  - Ligands
MH  - *Ovarian Neoplasms/pathology
MH  - Prognosis
MH  - *Receptors, CXCR4/genetics/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - CXCR4 receptor
OT  - Ovarian cancer
OT  - biomarkers
OT  - chemokine CXCL12
OT  - immunohistochemistry
OT  - prognosis
EDAT- 2023/06/23 19:11
MHDA- 2023/06/26 06:41
CRDT- 2023/06/23 12:13
PHST- 2023/05/07 00:00 [received]
PHST- 2023/05/23 00:00 [revised]
PHST- 2023/05/24 00:00 [accepted]
PHST- 2023/06/26 06:41 [medline]
PHST- 2023/06/23 19:11 [pubmed]
PHST- 2023/06/23 12:13 [entrez]
AID - 43/7/3331 [pii]
AID - 10.21873/anticanres.16509 [doi]
PST - ppublish
SO  - Anticancer Res. 2023 Jul;43(7):3331-3340. doi: 10.21873/anticanres.16509.