Zhang Fang, Wang Yali, Li Hongjuan, Li Li, Yang Xiaofeng, You Xiaoyan, Tang Lina
Department of Obstetrics and Gynecology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Metabolic Disease Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Front Oncol. 2023 Feb 28;13:1118906. doi: 10.3389/fonc.2023.1118906. eCollection 2023.
Leukemia inhibitory factor (LIF) exhibits significant tumor-promoting function, while its cognate receptor (LIFR) is considered to act as either a tumor promoter or suppressor. Dysregulation of LIF and LIFR is associated with the initiation, progression and metastasis of multiple cancer entities. Although increasing numbers of studies are revealing an indispensable critical role of LIFR in tumorigenesis for various different cancers, no systematic analysis of LIFR has appeared thus far.
Here, we comprehensively analyzed the expression profile and prognostic value of LIFR, and correlations between LIFR and the infiltration of immune cells and clinicopathological parameters across different tumor types using several bioinformatic tools. The expression profile of LIFR in various tumor types and clinical stages was investigated using the TIMER2 and GEPIA2 databases. Genetic alternations of LIFR were extracted from cBioPortal. The prognostic value of LIFR was assessed using GEPIA2 and Sanger box databases, and correlations between LIFR expression and immune infiltration were analyzed using the CIBERSORT method and TIMER2 database. The correlations between LIFR expression and immune and stromal scores were assessed using ESTIMATE. We also analyzed correlations between LIFR and immunoregulators. Finally, we detected an effect of LIFR on Uterine Corpus Endometrial Carcinoma (UCEC) and evaluated the expression level of LIFR in clinical UCEC samples.
Aberrant expression of LIFR in cancers and its prognosis ability, especially in UCEC was documented. Significantly lower levels of LIFR expression level correlated with better prognosis in multiple tumor types. LIFR expression was positively correlated with the abundance of cancer-associated fibroblasts (CAFs) and endothelial cells in the tumor microenvironment. Additionally, LIFR expression was strongly associated with the presence of immune modulators and checkpoint genes. Overexpression of LIFR suppressed the migration and invasion of UCEC cells .
Our pan-cancer detection data provided a novel understanding of the roles of LIFR in oncogenesis.
白血病抑制因子（LIF）具有显著的促肿瘤功能，而其同源受体（LIFR）被认为既可以作为肿瘤促进因子，也可以作为肿瘤抑制因子。LIF和LIFR的失调与多种癌症实体的发生、发展和转移有关。尽管越来越多的研究揭示了LIFR在各种不同癌症的肿瘤发生中起着不可或缺的关键作用，但迄今为止尚未出现对LIFR的系统分析。
在此，我们使用多种生物信息学工具，全面分析了LIFR的表达谱和预后价值，以及LIFR与不同肿瘤类型中免疫细胞浸润和临床病理参数之间的相关性。使用TIMER2和GEPIA2数据库研究了LIFR在各种肿瘤类型和临床阶段的表达谱。从cBioPortal中提取LIFR的基因改变。使用GEPIA2和Sanger box数据库评估LIFR的预后价值，并使用CIBERSORT方法和TIMER2数据库分析LIFR表达与免疫浸润之间的相关性。使用ESTIMATE评估LIFR表达与免疫和基质评分之间的相关性。我们还分析了LIFR与免疫调节因子之间的相关性。最后，我们检测了LIFR对子宫内膜癌（UCEC）的影响，并评估了临床UCEC样本中LIFR的表达水平。
记录了LIFR在癌症中的异常表达及其预后能力，尤其是在UCEC中。在多种肿瘤类型中，LIFR表达水平显著降低与较好的预后相关。LIFR表达与肿瘤微环境中癌症相关成纤维细胞（CAF）和内皮细胞的丰度呈正相关。此外，LIFR表达与免疫调节剂和检查点基因的存在密切相关。LIFR的过表达抑制了UCEC细胞的迁移和侵袭。
我们的泛癌检测数据为LIFR在肿瘤发生中的作用提供了新的认识。
