Dong Yanru, Wen Weibo, Yuan Tiezheng, Liu Lan, Li Xiangdan
Department of Morphological Experiment Center, Medical College of Yanbian University Yanji 133000, Jilin, China.
Department of Pathology, Yanbian University Hospital Yanji 133000, Jilin, China.
Am J Transl Res. 2023 Feb 15;15(2):1072-1084. eCollection 2023.
Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is one of the most common tumors among females worldwide. RILPL2 was recently reported to be a promising biomarker for the treatment of breast cancer. This study aimed to investigate the potential role of RILPL2 in CESC. Totally 302 CESC patients' data were downloaded from The Cancer Genome Atlas database. All patients were divided into high or low RILPL2 groups according to the median expression of RILPL2. Subsequently, survival analysis, multivariate Cox regression, and experimental validation were performed on all CESC patient data. The Ualcan database was used to analyze the expression level and prognostic value of RILPL2 in pan-cancer. The Gene Set Cancer Analysis database was used for drug sensitivity analysis. Functional KEGG pathways were analyzed using gene set enrichment analysis. RILPL2 was generally down-regulated in a variety of tumors, and a high level of RILPL2 was associated with a better prognosis in CESC patients. Immunohistochemistry, western blotting, and qRT-PCR results showed that RILPL2 was significantly down-regulated in CESC cells and tissues. Besides, along with the increase of TNM Stage, the RILPL2 expression tended to decrease gradually. Patients with high RILPL2 expression showed lower resistance to small molecule drugs used in CESC progressions, such as Methotrexate, AZD7762, and Vinblastine, and a higher response rate to immunotherapy. Additionally, we identified 267 co-expressing genes of RILPL2, all of which jointly affected CESC progression through 15 complex pathways. Low RILPL2 expression was closely associated with the onset, progression, and poor prognosis of CESC. RILPL2 might be a promising optional biomarker for CESC patients' diagnosis and prognosis.
宫颈鳞状细胞癌和宫颈管腺癌(CESC)是全球女性中最常见的肿瘤之一。最近有报道称RILPL2是一种有前景的乳腺癌治疗生物标志物。本研究旨在探讨RILPL2在CESC中的潜在作用。从癌症基因组图谱数据库下载了总共302例CESC患者的数据。根据RILPL2的中位表达将所有患者分为RILPL2高表达组或低表达组。随后,对所有CESC患者数据进行生存分析、多变量Cox回归分析和实验验证。使用Ualcan数据库分析RILPL2在泛癌中的表达水平和预后价值。使用基因集癌症分析数据库进行药物敏感性分析。使用基因集富集分析对KEGG功能通路进行分析。RILPL2在多种肿瘤中普遍下调,CESC患者中RILPL2水平高与较好的预后相关。免疫组织化学、蛋白质免疫印迹和qRT-PCR结果表明,RILPL2在CESC细胞和组织中显著下调。此外,随着TNM分期的增加,RILPL2表达呈逐渐下降趋势。RILPL2高表达的患者对CESC进展中使用的小分子药物(如甲氨蝶呤、AZD7762和长春碱)的耐药性较低,对免疫治疗的反应率较高。此外,我们鉴定出267个RILPL2的共表达基因,所有这些基因通过15条复杂通路共同影响CESC进展。RILPL2低表达与CESC的发生、发展及不良预后密切相关。RILPL2可能是CESC患者诊断和预后的一种有前景的可选生物标志物。