Gene expression profiling by targeted RNA sequencing in pathological stage I lung adenocarcinoma with a solid component

Yoshiteru Kidokoro; Tomohiko Sakabe; Tomohiro Haruki; Taichi Kadonaga; Kanae Nosaka; Hiroshige Nakamura; Yoshihisa Umekita

doi:10.1016/j.lungcan.2020.06.035

Gene expression profiling by targeted RNA sequencing in pathological stage I lung adenocarcinoma with a solid component

Lung Cancer. 2020 Sep:147:56-63. doi: 10.1016/j.lungcan.2020.06.035. Epub 2020 Jul 1.

Authors

Yoshiteru Kidokoro¹, Tomohiko Sakabe², Tomohiro Haruki³, Taichi Kadonaga¹, Kanae Nosaka², Hiroshige Nakamura³, Yoshihisa Umekita⁴

Affiliations

¹ Division of Pathology, Department of Pathology, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan; Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
² Division of Pathology, Department of Pathology, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
³ Division of General Thoracic Surgery, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan.
⁴ Division of Pathology, Department of Pathology, Department of Surgery, Faculty of Medicine, Tottori University, Tottori, Japan. Electronic address: yume@tottori-u.ac.jp.

PMID: 32673827
DOI: 10.1016/j.lungcan.2020.06.035

Abstract

Objectives: Solid predominant adenocarcinoma is considered an independent predictor of an unfavorable prognosis in patients with stage I lung adenocarcinoma (LUAD). Furthermore, solid minor components are related to poor prognosis in patients with stage I LUAD. Therefore, it is imperative to elucidate the molecular determinants of the malignant potential of solid components (SC). Several studies reported the gene expression profiling specific for lepidic predominant adenocarcinoma or solid predominant adenocarcinoma, however; there is no report identifying the differentially expressed genes (DEGs) between SC and acinar component (AC) within the same tumor tissue in pathological (p)-stage I LUAD patients.

Materials and methods: LUAD tissue samples containing both SC and AC were obtained from 8 patients with p-stage I LUAD and each component was microdissected. Targeted RNA sequencing was performed by a high-throughput chip-based approach.

Results: In total, 1272 DEGs were identified, including 677 upregulated genes and 595 downregulated genes in SC compared with AC. The most highly upregulated gene was TATA binding protein associated factor 7 (TAF7) and the most highly downregulated gene was homeobox B3 (HOXB3), which acts as a metastasis suppressor. A protein-protein interaction (PPI) network analysis of upregulated genes in SC identified ribosomal protein S27a (RPS27a) as a hub gene with the highest degree. First neighbors of RPS27a included PSMA6, which is a highly promising target for lung cancer. The subnetwork of PD-L1 had 10 first neighbors, including CMTM6, which enhances the ability of PD-L1-expressing tumor cells to inhibit T cells. The staining score for PD-L1 in SC was significantly higher than that in AC by immunohistochemistry (p = 0.001).

Conclusion: Our results revealed several new DEGs and key PPI network in SC compared to AC, contributing to understanding the biological features of SC and providing therapeutic targets for early-stage LUAD with SC in the future.

Keywords: Differentially expressed gene; Lung adenocarcinoma; Solid component.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung* / genetics
Biomarkers, Tumor
Gene Expression Profiling
Humans
Lung Neoplasms* / genetics
Proteasome Endopeptidase Complex
Sequence Analysis, RNA
TATA-Binding Protein Associated Factors*
Transcription Factor TFIID

Substances

Biomarkers, Tumor
TAF7 protein, human
TATA-Binding Protein Associated Factors
Transcription Factor TFIID
PSMA6 protein, human
Proteasome Endopeptidase Complex