Chen Mali, Zhang Lili, Liu Xiaolong, Ma Zhen, Lv Ling
Department of Obstetrics, Gansu Province Maternity and Child-Care Hospital, Lanzhou, China.
Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China.
Front Genet. 2021 Jun 17;12:697471. doi: 10.3389/fgene.2021.697471. eCollection 2021.
Period circadian protein homolog 1 (PER1) is an important component of the biorhythm molecular oscillation system and plays an important part in the development and progression of mammalian cancer. However, the correlations of PER1 with prognosis and tumor-infiltrating lymphocytes in ovarian cancer (OV) remain unclear. The Oncomine and TIMER databases were used to examine the expression of PER1 in OV. Kaplan-Meier Plotter and PrognoScan were used to evaluate the relationship between PER1 and prognosis. Kaplan-Meier Plotter was used to analyze the relationships between PER1 and clinicopathological features of OV patients. The relationship between PER1 expression and immune infiltration in OV was investigated using the TIMER database and CIBERSORT algorithm. The STRING database was used to analyze PER1-related protein functional groups, the GeneMANIA online tool was used to analyze gene groups with similar functions to those of PER1, and Network Analyst was used to identify transcription factors that regulate PER1. The correlation between PER1 and immunoinvasion of OV was analyzed using TIMER. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect PER1 expression. PER1 was differentially expressed in different cancer tissues, and its expression in various OV subtypes was lower than that in normal ovarian tissue. OV patients with low PER1 expression had a reduced overall survival rate. Decreased PER1 expression in stage 1 and stage 1+2 OV patients was related to poor prognosis, while increased PER1 expression in stage 3+4 patients and TP53 mutation were related to poor overall survival and progression-free survival. We identified eight genes whose expression was strongly correlated with that of PER1, as well as four transcription factors that regulate PER1. In OV, PER1 expression levels were positively correlated with infiltration levels of cells including neutrophils, regulatory T cells, and M2 macrophages, and closely related to a variety of immune markers. Reduced expression of PER1 was significantly associated with poor overall survival. These findings suggest that PER1 could be used as a prognostic biomarker to determine prognosis and immune infiltration in OV patients.
周期昼夜节律蛋白同源物1（PER1）是生物节律分子振荡系统的重要组成部分，在哺乳动物癌症的发生和发展中起重要作用。然而，PER1与卵巢癌（OV）预后及肿瘤浸润淋巴细胞的相关性仍不清楚。利用Oncomine和TIMER数据库检测PER1在OV中的表达。使用Kaplan-Meier Plotter和PrognoScan评估PER1与预后的关系。使用Kaplan-Meier Plotter分析PER1与OV患者临床病理特征的关系。利用TIMER数据库和CIBERSORT算法研究PER1表达与OV免疫浸润的关系。使用STRING数据库分析与PER1相关的蛋白质功能组，使用GeneMANIA在线工具分析与PER1功能相似的基因组，并使用Network Analyst识别调控PER1的转录因子。使用TIMER分析PER1与OV免疫侵袭的相关性。最后，进行定量实时聚合酶链反应（qRT-PCR）检测PER1表达。PER1在不同癌组织中差异表达，其在各种OV亚型中的表达低于正常卵巢组织。PER1表达低的OV患者总生存率降低。1期和1 + 2期OV患者PER1表达降低与预后不良有关，而3 + 4期患者PER1表达增加和TP53突变与总生存期和无进展生存期不良有关。我们鉴定出八个与PER1表达密切相关的基因，以及四个调控PER1的转录因子。在OV中，PER1表达水平与包括中性粒细胞、调节性T细胞和M2巨噬细胞在内的细胞浸润水平呈正相关，且与多种免疫标志物密切相关。PER1表达降低与总生存期差显著相关。这些发现表明，PER1可作为一种预后生物标志物，用于确定OV患者的预后和免疫浸润情况。
