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. 2025 Jul 14;25(1):1169.
doi: 10.1186/s12885-025-14496-z.

Gene expression in tumor and adjacent normal tissues in lung adenocarcinoma subtypes

Olga Y Gorlova #  1 , Ivan P Gorlov #  2 , R Taylor Ripley  1 , Chao Cheng  1 , Yafang Li  3 , Bo Peng  1 , Yanhong Liu  1 , Hee-Jin Jang  1 , Sung Wook Kang  1 , Claire Lee  1 , Priyanka Ranchod  1 , Bryan M Burt  4 , Hyun-Sung Lee  1 , Christopher I Amos  5   6
Affiliations

Gene expression in tumor and adjacent normal tissues in lung adenocarcinoma subtypes

Olga Y Gorlova et al. BMC Cancer. .

Abstract

Background: Lung adenocarcinoma (LUAD) has several histologically distinct subtypes that differ by a number of clinical features including patient survival. Molecular mechanisms underlying histological and clinical differences between subtypes remain poorly understood.

Methods: We conducted a comparative analyses of gene expression in acinar, lepidic, papillary and solid subtypes, as well as mucinous adenocarcinoma. We used a novel, more efficient approach to identify subtype-specific genes. We compared the mean gene expression level separately for tumors and adjacent normal tissue with pure or a highly represented (≥ 75%) subtype of interest to the mean expression in tumors where the subtype of interest was not present. We also performed tumor to adjacent normal tissue comparisons and identified genes differentially expressed between tumor and adjacent normal tissues for each subtype.

Results: The number of subtype-specific genes varied from 1 for the acinar to 482 for the papillary subtype. Comparative analysis of gene expression in adjacent normal tissues also identified subtype-specific genes, 38 in total. Gene set enrichment analysis identified oxidative phosphorylation as a biological function associated with papillary, and immune response - with solid subtype. Using data on differential expression between tumor and adjacent normal tissue among the subtype-specific genes and existing evidence for association with lung carcinogenesis, we have identified several candidate subtype-specific driver genes.

Conclusio: n We identified subtype-specific genes, biological functions, and potential drivers of subtype-specific carcinogenesis for LUAD subtypes. The study showed importance of gene expression in adjacent normal tissue for subtype-specific tumorigenesis.

Keywords: Gene expression; Lung adenocarcinoma (LUAD); Predominant subtypes.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval was granted by the Institutional Ethics Committee of Baylor College of Medicine, Houston, TX and written informed consent was obtained for all study participants (H-35782). The study was conducted in accordance with the principles of the Declaration of Helsinki. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Pairwise correlations of subtypes across tumors. Statistically significant correlations are shown in black boxes. Color coding is shown on the bottom. The numbers below the diagonal are correlation coefficients and the numbers above the diagonal are R2
See this image and copyright information in PMC

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