Gene expression profiling by targeted RNA sequencing in pathological stage I lung adenocarcinoma with a solid component
Gene expression profiling by targeted RNA sequencing in pathological stage I lung adenocarcinoma with a solid component
复制标题
DOI：
10.1016/j.lungcan.2020.06.035
复制
发表时间：
2020-09-01
期刊：
影响因子：
5.3
通讯作者：
Umekita, Yoshihisa
中科院分区：
文献类型：
--
作者：
Kidokoro, Yoshiteru;Sakabe, Tomohiko;Umekita, Yoshihisa
目的：实性占优势的腺癌被认为是I期肺腺癌患者预后不良的独立预测因子。此外，固体次要成分与I期LUAD患者预后不良有关。因此，有必要阐明固体成分(SC)恶性潜能的分子决定因素。已有多项研究报道了淋巴管型或实性型LUAD的特异性基因表达谱，但尚未发现病理(P)期LUAD患者同一肿瘤组织中SC和腺泡成分(AC)之间的差异表达基因(Degs)。材料和方法：取自8例p期LUAD患者的LUAD组织标本，并对每个成分进行显微解剖。结果：共鉴定出1272个基因，其中677个上调基因，595个下调基因。最高上调的基因是TATA结合蛋白相关因子7(TAF7)，最高下调的基因是同源盒B3(Hoxb3)，它起着转移抑制的作用。对SC上调基因的蛋白质-蛋白质相互作用(PPI)网络分析表明，核糖体蛋白S27a(RPS27a)是一个程度最高的HUB基因。RPS27a的第一个邻居包括PSMA6，它是一个非常有希望的肺癌靶点。PD-L1的亚网络有10个第一近邻，包括CMTM6，这增强了表达PD-L1的肿瘤细胞抑制T细胞的能力。免疫组织化学结果显示，SC中PD-L1的染色分数明显高于AC(p=0.001)。结论：与AC相比，SC中存在若干新的Deg和关键的PPI网络，有助于了解SC的生物学特性，为今后SC的早期LUAD提供治疗靶点。
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.