PTBP1 as a Promising Predictor of Poor Prognosis by Regulating Cell Proliferation, Immunosuppression, and Drug Sensitivity in SARC

Abstract

Background. 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. Methods. 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. Result. 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. Conclusions. 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.

LncRNA AC006064.4–201 serves as a novel molecular marker in alleviating cartilage senescence and protecting against osteoarthritis by destabilizing CDKN1B mRNA via interacting with PTBP1

“…As a member of the heterogeneous nuclear ribonucleoproteins (hnRNPs) family, PTBP1 is a widely studied RNA binding protein that binds to the polypyrimidine sequence on the pre-mRNA, and involves in regulating mRNA splicing, translation, stability and localization [ 42 , 43 ]. Previous studies have indicated that PTBP1 plays an important role in cancer progression [ 44 , 45 ], Alzheimer’s disease [ 46 , 47 ] and cardiac fibrosis [ 48 ].…”

Integrative analysis of TROAP with molecular features, carcinogenesis, and related immune and pharmacogenomic characteristics in soft tissue sarcoma

“…One important reason involves our understanding of the interaction between tumor and immune status in STS is insufficient, and there is a lack of new diagnostic and treatment prediction targets. Generally, tumor immune cell infiltration is recognized as an independent predictor of tumor immune status and survival 29 . Consequently, we further investigated the correlation between TROAP and tumor immune infiltration, trying to provide a new idea for explaining why TROAP affects the prognosis of STS.…”

A novel oncolytic virus-based biomarker participates in prognosis and tumor immune infiltration of glioma

“…PTBP1 is an RNA-binding protein with multifunctionality, involved in the regulatory process of mRNA splicing and apoptosis in numerous tumors and diseases ( Liu et al, 2023 ). In a study by Gong et al, it was suggested that PTBP1, being upregulated in pan-cancer, plays a role in mediating oncogenesis and immunity by influencing the growth and cell cycle of osteosarcoma cells ( Gong et al, 2022 ). According to previous studies, the downregulation of PTBP1 has been shown to impair immune surveillance, leading to the inhibition of inflammation-induced tumorigenesis ( Georgilis et al, 2018 ).…”