Yu Hao, Li Shuquan, Wu Yifan, Wang Zhen, Wang Xiaopeng, Zhang Sha, Guan Xiaoya, Dong Bin, Hao Chunyi, Tian Xiuyun, Lv Ang
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
Department of Critical Care Unit, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Int J Med Sci. 2025 Mar 10;22(8):1825-1836. doi: 10.7150/ijms.103802. eCollection 2025.
Retroperitoneal liposarcoma (RLPS) is a rare malignancy with no effective treatment beyond surgical intervention. Identifying novel therapeutic targets and prognostic markers is critical to improving outcomes. Fibroblast growth factor receptor substrate 2 (FRS2), located near MDM2 on chromosome 12q13-15, has a biological role and prognostic value in liposarcoma, which remain to be fully explored. Bioinformatics tools were used to analyze the differential expression of FRS2 across various malignancies using public databases, such as GTEx, TCGA, and cBioPortal. In sarcomas (SARC), clinicopathological features, prognostic outcomes, co-expressed genes, levels of tumor-infiltrating immune cells, immunostimulators, major histocompatibility complex (MHC) molecules, and immunochemokines were extracted from multiple public databases. Tumor specimens from 82 RLPS patients at our sarcoma center were collected, and FRS2 expression was assessed through immunohistochemistry. FRS2 was found to be upregulated and amplified in most cancers. GEPIA 2 analysis showed significant variation in FRS2 mRNA expression across cancer types, especially in sarcomas (SARC). Lower FRS2 expression in SARC was correlated with improved overall survival (OS) and disease-free survival (DFS). FRS2 may affect the tumor immune microenvironment, inhibiting immune cell infiltration and promoting immune evasion. In our RLPS cohort, FRS2 overexpression was observed in 58.53% (48/82) of cases and was correlated with age (P = 0.009). High FRS2 expression was associated with poorer OS and DFS (P = 0.049 and P < 0.001, respectively), and multivariate analysis confirmed FRS2 as an independent prognostic factor. FRS2 may serve as a potential prognostic biomarker and therapeutic oncogene target. Additionally, FRS2 could play a role in immune cell infiltration in SARC and represents a promising immunotherapeutic target for cancer treatment.
腹膜后脂肪肉瘤（RLPS）是一种罕见的恶性肿瘤，除手术干预外没有有效的治疗方法。确定新的治疗靶点和预后标志物对于改善治疗效果至关重要。成纤维细胞生长因子受体底物2（FRS2）位于12号染色体q13 - 15上的MDM2附近，在脂肪肉瘤中具有生物学作用和预后价值，仍有待充分探索。利用生物信息学工具，通过GTEx、TCGA和cBioPortal等公共数据库分析FRS2在各种恶性肿瘤中的差异表达。在肉瘤（SARC）中，从多个公共数据库中提取临床病理特征、预后结果、共表达基因、肿瘤浸润免疫细胞水平、免疫刺激剂、主要组织相容性复合体（MHC）分子和免疫趋化因子。收集了我们肉瘤中心82例RLPS患者的肿瘤标本，并通过免疫组织化学评估FRS2表达。发现FRS2在大多数癌症中上调并扩增。GEPIA 2分析显示FRS2 mRNA表达在不同癌症类型中存在显著差异，尤其是在肉瘤（SARC）中。SARC中较低的FRS2表达与总体生存期（OS）和无病生存期（DFS）的改善相关。FRS2可能影响肿瘤免疫微环境，抑制免疫细胞浸润并促进免疫逃逸。在我们的RLPS队列中，58.53%（48/82）的病例中观察到FRS2过表达，且与年龄相关（P = 0.009）。高FRS2表达与较差的OS和DFS相关（分别为P = 0.049和P < 0.001），多变量分析证实FRS2是一个独立的预后因素。FRS2可能作为潜在的预后生物标志物和治疗性癌基因靶点。此外，FRS2可能在SARC的免疫细胞浸润中起作用，是癌症治疗中一个有前景的免疫治疗靶点。
