Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Lung cancer (Amsterdam, Netherlands), 2020-09, Vol.147, p.56-63

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •DEGs between solid and acinar components in stage I lung adenocarcinoma were found.•In total, 1272 DEGs between SC and AC were identified.•TAF7 was highly expressed in the solid component.•RPS27a was a hub gene in a protein–protein interaction network analysis.•SC and AC exhibited distinct PD-L1 expression patterns. 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. 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. 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). 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.