CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지
Cancer Research and Treatment
; : 1203-1213, 2018.
Article
em En
| WPRIM
| ID: wpr-717747
Biblioteca responsável:
WPRO
ABSTRACT
PURPOSE:
This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). MATERIALS ANDMETHODS:
RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification.RESULTS:
The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency.CONCLUSION:
CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.Palavras-chave
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Radiação Ionizante
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Tolerância a Radiação
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Radioterapia
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Neoplasias Retais
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Dano ao DNA
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RNA Mensageiro
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Neoplasias Colorretais
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Linhagem Celular
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Reação em Cadeia da Polimerase
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Genes vif
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Research and Treatment
Ano de publicação:
2018
Tipo de documento:
Article