The role of PTRF/Cavin1 as a biomarker in both glioma and serum exosomes

Abstract

Exosomes play critical roles in intercellular communication in both nearby and distant cells in individuals and organs. Polymerase I and transcript release factor (PTRF), also known as Cavin1, has previously been described as a critical factor in caveola formation, and aberrant PTRF expression has been reported in various malignancies. However, the function of PTRF in tumor progression remains controversial, and its role in glioma is poorly understood. In this study, we report that PTRF is associated with malignancy grade and poor prognosis in glioma patients. Our previous study using two proteomics methods, tandem mass tag (TMT) and data-independent acquisition (DIA), showed that EGFRvIII overexpression increased PTRF expression at the protein level. In contrast, blocking PI3K and AKT using LY294002 and MK-2206, respectively, decreased PTRF expression, showing that PTRF is regulated in the EGFR/PI3K/AKT pathway. ChIP-PCR analysis showed that PTRF is transcriptionally regulated by the H3K4me3 and H3K27me3 modifications. Furthermore, PTRF overexpression increased exosome secretion and induced cell growth in vitro. More importantly, overexpressing PTRF induced the malignancy of nearby cells in vivo, suggesting that PTRF alters the microenvironment through intercellular communication via exosomes. Furthermore, analysis of clinical samples showed a positive correlation between tumor grade and PTRF expression in both tumor tissues and exosomes isolated from blood harvested from glioma patients, and PTRF expression in exosomes isolated from the sera of GBM patients was decreased after surgery. In conclusion, PTRF serves as a promising biomarker in both tumor samples and serum exosomes, thus facilitating the detection of glioma and potentially serving as a therapeutic target for glioblastoma multiforme.

Integrated profiling identifies caveolae‐associated protein 1 as a prognostic biomarker of malignancy in glioblastoma patients

“…Although a significant difference was not achieved, the result showed a tendency for lower levels of CAVIN1 expression to be correlated with better patient survival (Figure C, P = 0.0574; D, P = 0.0719). Second, we found that shorter patient survival was accompanied by higher expression of CAVIN1 in patients with wild‐type EGFR (Figure E,F and Figure S6A,B), which was consistent with the findings of a recent study . Lastly, the analysis combined with MGMT promoter methylation status demonstrated that there was no significant difference in CAVIN1 expression between the groups with methylated and unmethylated promoters (Figure S6C,D).…”

“…The knock‐down of CAVIN1 reduces multidrug resistance in breast cancer cell line MCF‐7/ADR cells . In GBM, it has been shown that CAVIN1 mediated chemoresistance in U251 cell lines, and its expression was upregulated in samples from relapsed GBM patients, but the number of patient samples was limited . A recent study identified an eight‐gene signature, including CAVIN1 that could predict the outcome of GBM patients .…”

Genome‐Wide CRISPR‐Cas9 Screening Identifies NF‐κB/E2F6 Responsible for EGFRvIII‐Associated Temozolomide Resistance in Glioblastoma

“…[25] Briefly, cells were lysed with radio immunoprecipitation assay (RIPA) buffer (Solarbio, Beijing, China) for total lysate extraction. [25] Briefly, cells were lysed with radio immunoprecipitation assay (RIPA) buffer (Solarbio, Beijing, China) for total lysate extraction.…”

A role for caveola‐forming proteins caveolin‐1 and CAVIN1 in the pro‐invasive response of glioblastoma to osmotic and hydrostatic pressure

“…7,8 In glioblastoma (GBM), caveolae or caveola-forming proteins have been proposed to be important in the regulation of EGFR signalling, resistance to treatment and exosome-mediated cell-cell communication. [9][10][11] Moreover, the expression of both caveolin-1 and CAVIN1 are increased in GBM compared to normal samples and are associated with shorter patient survival time and correlated with expression of the matrix proteases uPA and gelatinases. 12 Matrix proteases are key mediators of the invasiveness of GBM, which in turn contributes to the disease particularly poor prognosis.…”

“…The pressure‐sensing capabilities of caveolae and the mechanotransduction capacities of caveola‐forming proteins have pathophysiological consequences on cardiovascular or muscle function . In glioblastoma (GBM), caveolae or caveola‐forming proteins have been proposed to be important in the regulation of EGFR signalling, resistance to treatment and exosome‐mediated cell‐cell communication . Moreover, the expression of both caveolin‐1 and CAVIN1 are increased in GBM compared to normal samples and are associated with shorter patient survival time and correlated with expression of the matrix proteases uPA and gelatinases …”