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Abstract
Aims Conflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A could provide deeper insights into its prognostic implications and treatment determination.
Methods We conducted a search of articles in PubMed, EMBASE and the Cochrane Library from inception to January 2024. A domestic cohort consisting of 52 LUAD samples was subjected to whole-exome sequencing as internal validation. Data from The Cancer Genomic Atlas and the Gene Expression Omnibus datasets were obtained to characterise the genomic and immune profiles of LP+A. Pooled HRs and rates were calculated.
Results The pooled results indicated that lepidic growth pattern was either predominant (0.35, 95% CI 0.22 to 0.56, p<0.01) or minor (HR 0.50, 95% CI 0.36 to 0.70, p<0.01) histological subtype was associated with favourable disease-free survival. Pooled gene mutation rates suggested higher EGFR mutation (0.55, 95% CI 0.46 to 0.64, p<0.01) and lower KRAS mutation (0.14, 95% CI 0.02 to 0.25, p=0.02) in lepidic-predominant LUAD. Lepidic-predominant LUAD had lower tumour mutation burden and pooled positive rate of PD-L1 expression compared with other subtypes. LP+A was characterised by abundance in resting CD4+memory T cells, monocytes and γδ T cells, as well as scarcity of cancer-associated fibroblasts.
Conclusions LP+A was a unique histological subtype with a higher EGFR mutation rate, lower tumour mutation burden and immune checkpoint expression levels. Our findings suggested potential benefits from targeted therapy over immunotherapy in LP+A.
- Pathology, Molecular
- Lung Neoplasms
- GENETICS
Data availability statement
Data are available on reasonable request.
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Data availability statement
Data are available on reasonable request.
Footnotes
DC, YM and YC are joint senior authors.
Handling editor Vikram Deshpande.
YL, DC and YX contributed equally.
Contributors YueL, DC and YX made the conception, design, investigation and manuscript writing. YueL, QD, XX and YongzhongL made the data acquisition and interpretation. YC, YM and DC made the data analysis, manuscript writing and article review. YC is the guarantor. All authors edited the manuscript and approved the last version.
Funding Funded by National Natural Science Foundation of China (82172076); Key Scientific Program of Jiangsu Provincial Health Commission (ZD2021033); Project of Medical New Technology Assistance of the Second Affiliated Hospital of Soochow University (23ZL004, 23ZL012); The Project of Capacity Enhancement of Institutional Clinical Trials in Suzhou (SLT2023030); The Project of Clinical Innovation and Interdisciplinary Translation of Soochow University (ML12301623); The Construction Project of High-End Clinical Medical Technology Platform and Translational Base of Soochow University; Suzhou Youth Science and Technology Project of Revitalizing Health through Science and Education (KJXW2021013); Youth Scientific Funding of Zhongshan Hospital (Residency 2022-007, 2023ZSQN48).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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