Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University (The Second Military Medical University), Shanghai, China.
Department of Urology, Shanghai Changhai Hospital, Naval Medical University (The Second Military Medical University), Shanghai, China.
Oxid Med Cell Longev. 2022 May 23;2022:5687238. doi: 10.1155/2022/5687238. eCollection 2022.
Sarcomas (SARC) have been found as rare and heterogeneous malignancies with poor prognosis. PTBP1, belonging to the hnRNPs family, plays an essential role in some biological functions (e.g., pre-mRNA splicing, cell growth, and nervous system development). However, the role of PTBP1 in SARC remains unclear. In this study, the aim was to investigate the potential role of PTBP1 with a focus on SARC.
The expression, prognostic value, possible biological pathways of PTBP1, and its relationship with immune infiltration and drug sensitivity were comprehensively analyzed based on multiple databases. PTBP1 was further validated in osteosarcoma as the most prominent bone SARC. The expression of PTBP1 was investigated through IHC. The prognostic value of PTBP1 was verified in TARGET-OS databases. CRISPR/Cas9-mediated PTBP1 knockout HOS human osteosarcoma cell lines were used to assess the effect of PTBP1 on cell proliferation, migration, metastasis and cell cycle by CCK-8, Transwell migration, invasion, and FACS experiment.
PTBP1 was highly expressed and significantly correlated with poor prognosis in several cancers, especially in SARC, which was validated in the clinical cohort and osteosarcoma cell lines. The genetic alteration of PTBP1 was found most frequently in SARC. Besides, PTBP1 played a role in oncogenesis and immunity through cell cycle, TGFB, autophagy, and WNT pathways at a pan-cancer level. Knockout of PTBP1 was observed to negatively affect proliferation, migration, metastasis, and cell cycle of osteosarcoma in vitro. Furthermore, PTBP1 was significantly correlated with tumor immune infiltration, DNA methylation, TMB, and MSI in a wide variety of cancers. Moreover, the potential of the expression level of PTBP1 in predicting drug sensitivity was assessed.
PTBP1 is highly expressed and correlated with prognosis and plays a vital pathogenic role in oncogenesis and immune infiltration of various cancers, especially for SARC, which suggests that it may be a promising prognostic marker and therapeutic target in the future.
肉瘤（SARC）是一种罕见且异质性的恶性肿瘤，预后较差。PTBP1 属于 hnRNPs 家族，在一些生物学功能（如前体 mRNA 剪接、细胞生长和神经系统发育）中发挥重要作用。然而，PTBP1 在 SARC 中的作用尚不清楚。本研究旨在探讨 PTBP1 的潜在作用，并重点研究 SARC。
基于多个数据库，全面分析了 PTBP1 的表达、预后价值、可能的生物学途径及其与免疫浸润和药物敏感性的关系。PTBP1 在骨肉瘤中进一步验证为最显著的骨 SARC。通过免疫组织化学（IHC）研究 PTBP1 的表达。在 TARGET-OS 数据库中验证 PTBP1 的预后价值。使用 CRISPR/Cas9 介导的 PTBP1 敲除 HOS 人骨肉瘤细胞系，通过 CCK-8、Transwell 迁移、侵袭和 FACS 实验评估 PTBP1 对细胞增殖、迁移、转移和细胞周期的影响。
PTBP1 在几种癌症中高表达，与预后不良显著相关，尤其是在 SARC 中，在临床队列和骨肉瘤细胞系中得到验证。PTBP1 的遗传改变在 SARC 中最常见。此外，PTBP1 通过细胞周期、TGFB、自噬和 WNT 途径在泛癌水平上发挥致癌和免疫作用。体外敲除 PTBP1 观察到骨肉瘤的增殖、迁移、转移和细胞周期受到负面影响。此外，PTBP1 与多种癌症中的肿瘤免疫浸润、DNA 甲基化、TMB 和 MSI 显著相关。此外，评估了 PTBP1 表达水平预测药物敏感性的潜力。
PTBP1 高表达与预后相关，在多种癌症的肿瘤发生和免疫浸润中发挥重要的致病作用，尤其是在 SARC 中，这表明它可能是未来有前途的预后标志物和治疗靶点。
