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01-04-2022 | Original Article

Gene expression profiling using targeted RNA-sequencing to elucidate the progression from histologically normal lung tissues to non-invasive lesions in invasive lung adenocarcinoma

Authors: Taichi Kadonaga, Tomohiko Sakabe, Yoshiteru Kidokoro, Tomohiro Haruki, Kanae Nosaka, Hiroshige Nakamura, Yoshihisa Umekita

Published in: Virchows Archiv | Issue 4/2022

Abstract

Lung adenocarcinoma (LUAD) shows heterogeneous morphological features and the stepwise progression from adenocarcinoma in situ to minimally invasive adenocarcinoma to invasive LUAD. Although multiple genetic alterations have been linked to the progression, the differences between the gene expression profiles of non-invasive lesions (non-ILs) and adjacent histologically normal lung (aNL) tissues within invasive LUAD have not been investigated. Herein, we analyzed differentially expressed genes (DEGs) specific to early-stage carcinogenesis in LUAD. Invasive LUAD tissue samples containing both non-ILs and aNL tissues were obtained from seven patients with pathological stage I LUAD, and each component was subjected to microdissection. Gene expression profiles of each component were determined using targeted RNA-sequencing. In total, 2536 DEGs, including 863 upregulated and 1673 downregulated genes, were identified in non-ILs. In non-ILs, the expression of SLC44A5, a choline transporter-like protein-coding gene, was significantly upregulated, and that of TMEM100, a gene encoding a transmembrane protein, was significantly downregulated. Reportedly, SLC44A5 plays an important role in the development and progression of hepatocellular carcinoma, whereas TMEM100 functions as a tumor suppressor in non-small cell lung cancer. Gene set enrichment analysis showed that DEGs in non-ILs were negatively enriched in cell death and immune response. Immunohistochemical analysis revealed that increased SLC44A5 expression and decreased TMEM100 expression were maintained in ILs. A protein–protein interaction (PPI) network analysis identified several upregulated and downregulated hub genes with high degrees in non-ILs. In conclusion, several new DEGs and key PPI network hub genes were identified in non-ILs, contributing to understanding of early-stage carcinogenesis in LUAD.

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Title: Gene expression profiling using targeted RNA-sequencing to elucidate the progression from histologically normal lung tissues to non-invasive lesions in invasive lung adenocarcinoma
Authors: Taichi Kadonaga
Tomohiko Sakabe
Yoshiteru Kidokoro
Tomohiro Haruki
Kanae Nosaka
Hiroshige Nakamura
Yoshihisa Umekita
Publication date: 01-04-2022
Publisher: Springer Berlin Heidelberg
Published in: Virchows Archiv / Issue 4/2022
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-021-03250-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Gene expression profiling using targeted RNA-sequencing to elucidate the progression from histologically normal lung tissues to non-invasive lesions in invasive lung adenocarcinoma

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

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