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  • [J Nucl Med] Tumor Metabolic Features Identified by 18F-FDG PET Correlate with Gene Networks of Immune Cell Microenvironment in Head and Neck Cancer.

    [J Nucl Med] Tumor Metabolic Features Identified by 18F-FDG PET Correlate with Gene Networks of Immune Cell Microenvironment in Head and Neck Cancer.

    천안시보건소 / 나권중, 최홍윤*

  • 출처
    J Nucl Med
  • 등재일
    2018 Jan
  • 저널이슈번호
    59(1):31-37.
  • 내용

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    Abstract

    The importance of 18F-FDG PET in imaging head and neck squamous cell carcinoma (HNSCC) has grown in recent decades. Because PET has prognostic values, and provides functional and molecular information in HNSCC, the genetic and biologic backgrounds associated with PET parameters are of great interest. Here, as a systems biology approach, we aimed to investigate gene networks associated with tumor metabolism and their biologic function using RNA sequence and 18F-FDG PET data. Methods: Using RNA sequence data of HNSCC downloaded from The Cancer Genome Atlas data portal, we constructed a gene coexpression network. PET parameters including lesion-to-blood-pool ratio, metabolic tumor volume, and tumor lesion glycolysis were calculated. The Pearson correlation test was performed between module eigengene-the first principal component of modules' expression profile-and the PETparameters. The significantly correlated module was functionally annotated with gene ontology terms, and its hub genes were identified. Survival analysis of the significantly correlated module was performed. Results: We identified9 coexpression network modules from the preprocessed RNA sequence data. A network module was significantly correlated with total lesion glycolysis as well as maximum and mean 18F-FDG uptake. The expression profiles of hub genes of the network were inversely correlated with 18F-FDG uptake. The significantly annotated gene ontology terms of the module were associated with immune cell activation and aggregation. The module demonstrated significant association with overall survival, and the group with higher module eigengene showed better survival than the other groups with statistical significance (P = 0.022). Conclusion: We showed that a gene network that accounts for immune cell microenvironment was associated with 18F-FDG uptake as well as prognosis in HNSCC. Our result supports the idea that competition for glucose between cancer cell and immune cell plays an important role in cancerprogression associated with hypermetabolic features. In the future, PET parameters could be used as a surrogate marker of HNSCC for estimating molecular status of immune cell microenvironment.

     

     

    Author information

    Na KJ1,2, Choi H3.

    1 Department of Community Health, Korea Health Promotion Institution, Seoul, Republic of Korea chy1000@gmail.com.
    2 Department of Clinical Medical Sciences, Seoul National University, College of Medicine, Seoul, Republic of Korea; and.
    3 Department of Nuclear Medicine, Cheonan Public Health Center, Chungnam, Republic of Korea chy1000@gmail.com.

  • 키워드
    head and neck squamous cell carcinoma; next generation sequencing; positron emission tomography; tumormicroenvironment
  • 연구소개
    본 연구는 Tumor의 FDG uptake가 Systemic하게 어떤 요인들과 관련되는지를 조사하기 위한 과정의 결과입니다. 본 연구에서는 TCGA와 TCIA라는 public database를 활용해, Head and neck cancer에서의 RNA sequencing data와 FDG PET영상 데이터를 통합하여, transcriptome data에서 tumor glucose metabolism과 연관된 gene network module을 찾아 분석하였습니다. 그 결과 microenvironment의 immune activation정도와 반비례하는 상관관계가 있다는 것을 알 수 있었고, 전반적인 Immune cell enrichment와도 역상관관계가 있다는 사실을 볼 수 있었습니다. 최근의 cancer의 immune escape mechanism으로서 cancer와 microenvironment의 immune cell간 metabolic한 competition이 대두되고 있는데, 본 연구는 이와 같은 경쟁적 관계를 transcriptome과 image분석으로서 뒷받침하는 결과입니다.
  • 편집위원

    종양세포와 면역세포사이의 당대사 경쟁이 종양의 진행과 관련된 FDG 축적 상관성을 보여주었으며, 또한 이러한 결과가 예후와 상관성이 있음을 보여준 흥미로운 연구임. 유전자네트워크과 당대사 결과를 연결한 연구형태로 종양학 및 핵의학의 융합에 대한 관심을 가진 연구자에게 의미가 큰 논문으로 생각됩니다

    2018-02-07 11:53:18

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