Wang Feng, Du Hongjuan, Li Bibo, Luo Zhibin, Zhu Lei
Department of Oncology, Chongqing General Hospital, Chongqing, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Genet. 2022 Sep 6;13:941567. doi: 10.3389/fgene.2022.941567. eCollection 2022.
Unlocking phenotype plasticity (UPP) has been shown to have an essential role in the mechanism of tumor development and therapeutic response. However, the clinical significance of unlocking phenotypic plasticity in patients with lung adenocarcinoma is unclear. This study aimed to explore the roles of unlocking phenotypic plasticity in immune status, prognosis, and treatment in patients with lung adenocarcinoma (LUAD). Differentially expressed genes (DEGs) and clinical information of UPP were selected from the cancer genome atlas (TCGA) database, and the GO, KEGG enrichment analyses were performed. The independent prognostic genes were determined by univariate and multivariate Cox regression, and the UPP signature score was constructed. Patients with LUAD were divided into high- and low-risk groups according to the median of score, and the immunocytes and immune function, the gene mutation, and drug sensitivities between the two groups were analyzed. Finally, the results were validated in the GEO database. Thirty-nine significantly DEGs were determined. Enrichment analysis showed that UPP-related genes were related to protein polysaccharides and drug resistance. The prognostic results showed that the survival of patients in the high-risk group was poorer than that in the low-risk group ( < 0.001). In the high- and low-risk groups, single nucleotide polymorphism (SNP) and C > T are the most common dissent mutations. The contents of immune cells were significantly different between high- and low-risk groups. And the immune functions were also significantly different, indicating that UPP affects the immunity in LUAD. The results from TCGA were validated in the GEO. Our research has proposed a new and reliable prognosis indicator to predict the overall survival. Evaluation of the UPP could help the clinician to predict therapeutic responses and make individualized treatment plans in patients with LUAD.
解锁表型可塑性（UPP）已被证明在肿瘤发生发展机制和治疗反应中起重要作用。然而，解锁肺腺癌患者表型可塑性的临床意义尚不清楚。本研究旨在探讨解锁肺腺癌（LUAD）患者表型可塑性在免疫状态、预后及治疗中的作用。从癌症基因组图谱（TCGA）数据库中选取UPP的差异表达基因（DEGs）和临床信息，并进行基因本体（GO）、京都基因与基因组百科全书（KEGG）富集分析。通过单因素和多因素Cox回归确定独立预后基因，并构建UPP特征评分。根据评分中位数将LUAD患者分为高风险组和低风险组，分析两组之间的免疫细胞和免疫功能、基因突变及药物敏感性。最后，在基因表达综合数据库（GEO）中验证结果。确定了39个显著差异表达基因。富集分析表明，UPP相关基因与蛋白多糖和耐药性有关。预后结果显示，高风险组患者的生存率低于低风险组（<0.001）。在高风险组和低风险组中，单核苷酸多态性（SNP）和C>T是最常见的不同突变。高风险组和低风险组之间免疫细胞含量存在显著差异。免疫功能也有显著差异，表明UPP影响LUAD患者的免疫力。TCGA的结果在GEO中得到验证。我们的研究提出了一种新的可靠预后指标来预测总生存期。评估UPP有助于临床医生预测LUAD患者的治疗反应并制定个体化治疗方案。
