GP88/PGRN Serum Levels Are Associated with Prognosis for Oral Squamous Cell Carcinoma Patients

Greither, Thomas; Steiner, Tina; Bache, Matthias; Serrero, Ginette; Otto, Sven; Täubert, Helge; Eckert, Alexander W.; Kappler, Matthias

doi:10.3390/biology10050400

Cited by 4 publications

(4 citation statements)

References 62 publications

(82 reference statements)

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“…In the opposite situation, where miR-107 was upregulated and PGRN was downregulated, the promotion of sensitivity of PC-3 cells to ionizing radiation was observed. Other available studies showed that PGRN serum concentration levels in patients with oral squamous cell carcinomas (OSCCs) are not associated with susceptibility levels to radiation therapy [150]. These findings could also suggest that PGRN-related pathomechanisms could be involved in tumour resistance to radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme

Poniatowski,

Woźnica,

Wojdasiewicz

et al. 2024

Cells

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Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

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Section: Discussionmentioning

confidence: 99%

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme

Poniatowski,

Woźnica,

Wojdasiewicz

et al. 2024

Cells

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“…However, increased GP88 protein levels in tumor tissues or increased GP88 protein levels in serum have been associated with increased aggressiveness and poor long-term prognosis in different cancers, including PCa [ 14 ]. In addition, an increase in GP88 protein has been described in relation to different cancer treatment resistance mechanisms [ 46 ], especially in endocrine-related tumors, such as letrozole and tamoxifen resistance in breast cancer cells [ 20 , 47 ] and chemoresistance to cisplatin in ovarian cancer cell lines [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Combined miR-486 and GP88 (Progranulin) Serum Levels Are Suggested as Supportive Biomarkers for Therapy Decision in Elderly Prostate Cancer Patients

Fichte

Neumann

Weigelt

et al. 2022

Life

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Our study aimed to assess the applicability of miR-486 in combination with soluble GP88 protein as a diagnostic and/or predictive biomarker for prostate cancer (PCa) patients. miR-486 and GP88 levels in serum samples from 136 patients undergoing MRI-guided biopsy of the prostate were assessed by qRT–PCR and ELISA, respectively. Of these, 86 patients received a histologically confirmed diagnosis of PCa. Neither marker showed an association with the diagnosis of cancer. PCa patients were separated based on (i) treatment into patients with active surveillance or patients with any type of curative treatment and (ii) age into elderly (>68 years) patients and younger patients (≤68 years). In elderly patients (N = 41) with the intention of curative treatment at optimized cut-off values, significantly higher GP88 levels (p = 0.018) and lower miR-486 levels (p = 0.014) were observed. The total PSA level and ISUP biopsy grade were used in a baseline model for predicting definitive therapy. The baseline model exhibited an area under the curve (AUC) of 0.783 (p = 0.005). The addition of the serum biomarkers miR-486 and GP88 to the baseline model yielded an improved model with an AUC of 0.808 (p = 0.002). Altogether, combined miR-486 and GP88 serum levels are associated with and are therefore suggested as supportive biomarkers for therapy decisions, particularly in elderly PCa patients.

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“…Finally, the potential use of progranulin as a prognostic marker is also currently under investigation in other tumors, such as oral squamous cell carcinomas [ 133 ], advanced biliary tract carcinoma [ 134 ], gastrointestinal tumors [ 135 ] and papillary thyroid cancer [ 136 ].…”

Section: Progranulin In Solid Tumorsmentioning

confidence: 99%

Progranulin Oncogenic Network in Solid Tumors

Ventura

Ducci

Dominguez

et al. 2023

Cancers

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Progranulin is a pleiotropic growth factor with important physiological roles in embryogenesis and maintenance of adult tissue homeostasis. While-progranulin deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia and neuronal ceroid lipofuscinosis, progranulin upregulation characterizes many tumors, including brain tumors, multiple myeloma, leiomyosarcoma, mesothelioma and epithelial cancers such as ovarian, liver, breast, bladder, adrenal, prostate and kidney carcinomas. The increase of progranulin levels in tumors might have diagnostic and prognostic significance. In cancer, progranulin has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth and resistance to chemotherapy. In addition, progranulin regulates the tumor microenvironment, affects the function of cancer-associated fibroblasts, and modulates tumor immune surveillance. However, the molecular mechanisms of progranulin oncogenic function are not fully elucidated. In bladder cancer, progranulin action relies on the activation of its functional signaling receptor EphA2. Notably, more recent data suggest that progranulin can also modulate a functional crosstalk between multiple receptor-tyrosine kinases, demonstrating a more complex and context-dependent role of progranulin in cancer. Here, we will review what is currently known about the function of progranulin in tumors, with a focus on its molecular mechanisms of action and regulation.

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GP88/PGRN Serum Levels Are Associated with Prognosis for Oral Squamous Cell Carcinoma Patients

Cited by 4 publications

References 62 publications

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme

Combined miR-486 and GP88 (Progranulin) Serum Levels Are Suggested as Supportive Biomarkers for Therapy Decision in Elderly Prostate Cancer Patients

Progranulin Oncogenic Network in Solid Tumors

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