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Genomic discordances and heterogeneous mutational burden, PD-L1 expression and immune infiltrates of non-small cell lung cancer metastasis
  1. Jianghua Wu1,
  2. Luning Mao1,
  3. Wanjun Lei2,
  4. Wei Sun1,
  5. Xin Yang1,
  6. Yanhui Zhang3,
  7. Xiaozheng Huang1,
  8. Dongmei Lin1
  1. 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China
  2. 2Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, China
  3. 3Department of Pathology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy; Tianjin’s Clinical Research Center of Cancer, Tianjin, China
  1. Correspondence to Professor Dongmei Lin, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, 100142 Beijing, China; lindm3{at}163.com

Abstract

Aims To investigate the genomic discordances and heterogeneous mutational burden, PD-L1 expression and immune cell (IC) infiltrates of non-small cell lung cancer (NSCLC) metastasis.

Methods Surgical samples from 41 cases of NSCLC with metastatic tumours (MTs) and paired primary tumours (PTs) were collected. PD-L1 expression and ICs were quantified using image-based immunohistochemistry profiling. Whole exome sequencing was employed to explore discrepancies in genomic characteristics, tumour mutational burden (TMB) and tumour neoantigen burden (TNB) in 28 cases.

Results Non-synonymous mutations in MTs were slightly more than in PTs, with only 42.34% of mutations shared between paired PTs and MTs. The heterogeneity of TMB showed no significant difference (p=0.785) between MTs and PTs, while TNB significantly increased in MTs (p=0.013). MTs generally exhibited a higher density of PD-L1+ cells and a higher tumour proportion score with a lower density of IC infiltrates. Subgroup analysis considering clinicopathological factors revealed that the heterogeneity of immune biomarkers was closely associated with the histology of lung adenocarcinoma, metastatic sites of extrapulmonary, time intervals and treatment history. Prognosis analysis indicated that a high density of CD8+ T cells was a low-risk factor, whereas a high density of PD-L1+ cells in MTs was a high-risk factor for cancer-related death in metastatic NSCLC.

Conclusions The mutational burden, PD-L1 expression and IC infiltrates undergo changes during NSCLC metastasis, which may impact the immunotherapeutic benefits in patients with NSCLC with metastatic progression and should be monitored according to clinical scenarios.

  • Biomarkers, Tumor
  • Lung Neoplasms
  • Pathology, Molecular

Data availability statement

Data are available upon reasonable request. Not applicable.

https://doi.org/10.1136/jcp-2023-209328

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    Data availability statement

    Data are available upon reasonable request. Not applicable.

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    Footnotes

    • Handling editor Vikram Deshpande.

    • JW, LM and WL contributed equally.

    • Presented at The study was originally presented as an abstract, available at https://doi.org/10.1016/j.jtho.2023.09.220.

    • Contributors DL is responsible for the overall content as the guarantor. JW contributed to data statistics and manuscript writing and participated in the experimental design. LM contributed to immunohistochemistry and digital image analysis. WL contributed to whole exome sequencing and bioinformatics analysis. WS and XY collected the clinical information and follow-up data of the cases. YZ and XH prepared the slides and tissues. DL conceived the study, participated in its design and coordination, and assisted in drafting and editing the manuscript.

    • Funding This work was supported by the National Natural Science Foundation of China (81871860 and 82003155).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.