Genetic and immune characteristics of multiple primary lung cancers and lung metastases.

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  • Additional Information
    • Source:
      Publisher: Wiley Publishing Asia Pty Ltd Country of Publication: Singapore NLM ID: 101531441 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1759-7714 (Electronic) Linking ISSN: 17597706 NLM ISO Abbreviation: Thorac Cancer Subsets: MEDLINE
    • Publication Information:
      Publication: November 2012- : Singapore : Tianjin : Wiley Publishing Asia Pty Ltd ; Tianjin Lung Cancer Institute
      Original Publication: Richmond, Vic. : Tianjin : Blackwell Pub. Asia Pty Ltd. ; Tianjin Lung Cancer Institute
    • Subject Terms:
      Lung Neoplasms/*genetics ; Lung Neoplasms/*immunology ; Neoplasms, Multiple Primary/*genetics ; Neoplasms, Multiple Primary/*immunology; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/immunology ; Humans ; Lung Neoplasms/pathology ; Neoplasms, Multiple Primary/pathology ; Exome Sequencing
    • Abstract:
      Background: To explore the genetic and immunophenotyping heterogeneities between patients with intrapulmonary metastasis (IPM) or multiple primary lung cancer (MPLC).
      Methods: Whole exome sequencing (WES) and transcriptome sequencing (RNA-seq) were performed on the tissue and blood samples of IPM and MPLC patients to comprehensively analyze the clonal evolution, molecular typing and immunophenotyping.
      Results: There was no significant difference in genetic mutation, tumor mutational burden (TMB) value and mutant allele tumor heterogeneity (MATH) value between IPM and MPLC patients. Notably, the loss of heterozygosity (LOH) of human leukocyte antigen (HLA) appeared in all IPM patients, while there was also no significant difference between the two groups. In addition, expression of immune checkpoint-related genes including CTLA-4, BTLA, TIGIT and HAVCR2 in the MPLC group was significantly higher than those in IPM group. At the same time, 86 differentially expressed genes (DEGs) were observed between IPM and MPLC patients with transcriptome sequencing, of which 56 DEGs were upregulated and 30 were downregulated in the IPM group compared with the MPLC group. The cluster analysis revealed that the 86 DEGs could be distinguished in IPM and MPLC samples. Moreover, only the infiltration levels of CD56dim natural killer cells in the IPM group was significantly higher than that in the MPLC group, and the infiltration levels of the remaining 27 immune cell subsets were similar in both groups.
      Conclusions: IPM and MPLC are roughly similar in genetic and immune characteristics indicating that genomics alone may not be able to effectively distinguish between IPM and MPLC, which still needs to be comprehensively evaluated with clinical manifestations, imaging, and pathological characteristics.
      (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)
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    • Contributed Indexing:
      Keywords: intrapulmonary metastasis; multiple primary lung cancer; transcriptome sequencing; tumor-infiltrating lymphocyte; whole exome sequencing
    • Accession Number:
      0 (Biomarkers, Tumor)
    • Publication Date:
      Date Created: 20210912 Date Completed: 20220126 Latest Revision: 20221207
    • Publication Date:
      20240829
    • Accession Number:
      PMC8487821
    • Accession Number:
      10.1111/1759-7714.14134
    • Accession Number:
      34510768