CCR5 promoter polymorphisms associated with nonsmall cell lung cancer
Tianchang Lu
Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Search for more papers by this authorYuhan Shi
College of Agronomy and Biotechnology of Yunnan Agricultural University, Kunming, China
Search for more papers by this authorMinyi Wang
School of Life Science, Yunnan University, Kunming, China
Search for more papers by this authorWeipeng Liu
Institute of Medical Biology, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Search for more papers by this authorYang Cao
Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
Search for more papers by this authorLi Shi
Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Search for more papers by this authorCorresponding Author
Qianli Ma
Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
Correspondence
Shuyuan Liu, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.
Email: [email protected]
Qianli Ma, Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Shuyuan Liu
Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Correspondence
Shuyuan Liu, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.
Email: [email protected]
Qianli Ma, Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
Email: [email protected]
Search for more papers by this authorTianchang Lu
Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Search for more papers by this authorYuhan Shi
College of Agronomy and Biotechnology of Yunnan Agricultural University, Kunming, China
Search for more papers by this authorMinyi Wang
School of Life Science, Yunnan University, Kunming, China
Search for more papers by this authorWeipeng Liu
Institute of Medical Biology, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Search for more papers by this authorYang Cao
Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
Search for more papers by this authorLi Shi
Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Search for more papers by this authorCorresponding Author
Qianli Ma
Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
Correspondence
Shuyuan Liu, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.
Email: [email protected]
Qianli Ma, Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Shuyuan Liu
Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China
Correspondence
Shuyuan Liu, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.
Email: [email protected]
Qianli Ma, Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
Email: [email protected]
Search for more papers by this authorAbstract
C–C chemokine receptor 5 (CCR5) plays a crucial role in the regulation of immune cell activation and migration as well as the progression of many cancers. We performed an in silico analysis using public data resources and found that the lung cancer patients with higher CCR5 expression had a notably better overall survival than those with lower CCR5 expression patients and CCR5 expression level is positive correlated with the infiltration of immune cells, such as B, CD8+ T and CD4+ T cells, in both lung adenocarcinoma and lung squamous cell cancer. In the present study, we investigated the association between the promoter polymorphism of CCR5 and nonsmall cell lung cancer (NSCLC). A case‒control study of 449 NSCLC patients and 516 controls of Chinese Han population was conducted, along with polymorphism detection using a sequencing method. A dual-luciferase reporter assay system was used to analyse the transcriptional activity of CCR5 promoter variations. Our results showed that the frequency of rs1799987-AA was significantly higher in the NSCLC group than in the controls in recessive model (p = .007, OR = 1.66 95% confidence interval [CI]: 1.14–2.40, adjusted by sex and age); the G allele showed a significant associated with NSCLC in dominant model (p = .003, OR = 1.64, 95%CI: 1.18–2.28, adjusted by sex and age). Compared with haplotype H1 rs2227010–rs2734648–rs1799987–rs1799988–rs1800023–rs1800024: A-T-G-T-G-C, haplotype H5: A-G-G-T-G-C increased the risk of NSCLC by over 10-fold (p < .0001, OR = 16.09, 95%CI: 5.37–48.20, adjusted by sex and age) and notably depressed the transcriptional activity of the CCR5 promoter in 293T, A549, H1299 and HeLa cells. In conclusion, CCR5 promoter polymorphisms are significantly associated with NSCLC by affecting the transcriptional activity of the CCR5 promoter.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are openly available in the Figshare database. DOI: 10.6084/m9.figshare.22331320.
Supporting Information
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