Shen Kaiyu, Chen Binyu, Yang Liu, Gao Wencang
The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, China.
Department of Oncology, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310005, China.
Int J Genomics. 2023 Nov 2;2023:4662480. doi: 10.1155/2023/4662480. eCollection 2023.
Kynureninase (KYNU) is a potential prognostic marker for various tumor types. However, no reports on the biological effects and prognostic value of KYNU in gastric cancer (GC) exist.
GC-associated single-cell RNA sequencing and bulk RNA sequencing (bulk-seq) data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. The differential expression of KYNU between GC and normal gastric tissues was first analyzed based on the bulk-seq data, followed by an exploration of the relationship between KYNU and various clinicopathological features. The Kaplan-Meier survival and Cox regression analyses were performed to determine the prognostic value of KYNU. The relationship between KYNU expression and immune cell infiltration and immune checkpoints was also explored. The biological function of KYNU was further examined at the single-cell level, and in vitro experiments were performed to examine the effect of KYNU on GC cell proliferation and invasion.
KYNU expression was significantly elevated in GC samples. Clinical features and survival analysis indicated that high KYNU expression was associated with poor clinical phenotypes and prognosis, whereas Cox analysis showed that KYNU was an independent risk factor for patients with GC. Notably, high expression of KYNU induced a poor immune microenvironment and contributed to the upregulation of immune checkpoints. KYNU-overexpressing macrophages drove GC progression through unique ligand-receptor pairs and transcription factors and were associated with adverse clinical phenotypes in GC. KYNU was overexpressed in GC cells in vitro, and KYNU knockout significantly inhibited GC cell proliferation and invasion.
High KYNU expression promotes an adverse immune microenvironment and low survival rates in GC. KYNU and KYNU-related macrophages may serve as novel molecular targets in the treatment of GC.
犬尿氨酸酶（KYNU）是多种肿瘤类型的潜在预后标志物。然而，目前尚无关于KYNU在胃癌（GC）中的生物学效应和预后价值的报道。
分别从基因表达综合数据库和癌症基因组图谱数据库中获取与GC相关的单细胞RNA测序和批量RNA测序（bulk-seq）数据。首先基于bulk-seq数据分析GC组织与正常胃组织中KYNU的差异表达，随后探讨KYNU与各种临床病理特征之间的关系。进行Kaplan-Meier生存分析和Cox回归分析以确定KYNU的预后价值。还探讨了KYNU表达与免疫细胞浸润及免疫检查点之间的关系。在单细胞水平上进一步研究KYNU的生物学功能，并进行体外实验以检测KYNU对GC细胞增殖和侵袭的影响。
KYNU在GC样本中的表达显著升高。临床特征和生存分析表明，KYNU高表达与不良临床表型和预后相关，而Cox分析显示KYNU是GC患者的独立危险因素。值得注意的是，KYNU的高表达诱导了不良的免疫微环境，并导致免疫检查点上调。过表达KYNU的巨噬细胞通过独特的配体-受体对和转录因子驱动GC进展，并与GC的不良临床表型相关。KYNU在体外GC细胞中过表达，敲除KYNU可显著抑制GC细胞的增殖和侵袭。
KYNU高表达促进GC中不良的免疫微环境和低生存率。KYNU及与KYNU相关的巨噬细胞可能成为GC治疗中的新型分子靶点。
