Genetic and immune characteristics of multiple primary lung cancers and lung metastases. Issue 19 (12th September 2021)

• Record Type: Journal Article
• Authors: Yang, Ronghua; Li, Peng; Wang, Dong; Wang, Lingjie; Yin, Jihui; Yu, Baohua; Li, Mengjun; Wang, Sai; Wang, Yongjie
• Is Part Of: Thoracic cancer. Volume 12:Issue 19(2021)
• Page Start: 2544
• Page End: 2550
• Publication Date: 2021-09-12
• Subjects: intrapulmonary metastasis -- multiple primary lung cancer -- transcriptome sequencing -- tumor‐infiltrating lymphocyte -- whole exome sequencing; Chest -- Cancer -- Periodicals; Chest -- Cancer -- Treatment -- Periodicals; Chest -- Surgery -- Periodicals; 616.99494005
• DOI: 10.1111/1759-7714.14134
• Languages: English
• ISSNs: 1759-7706

Abstract

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. Abstract : We evaluated the genetic and immunophenotyping heterogeneities between patients with intrapulmonary metastasis (IPM) or multiple primary lung cancer (MPLC) by whole exome sequencing (WES) and transcriptome sequencing (RNA‐seq). The results found that compared with MPLC, the HLA‐LOH frequency and the infiltration levels of CD56dim natural killer cells in IPM was higher, and expressions of immune checkpoint‐related genes including CTLA‐4, BTLA, TIGIT and HAVCR2 was lower.