Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas

Jennewein, Lukas; Ronellenfitsch, Michael; Antonietti, Patrick; Ilina, Elena I.; Jung, Jennifer; Stadel, Daniela; Flohr, Lisa-Marie; Zinke, Jenny; Renesse, Janusz von; Drott, Ulrich; Baumgarten, Peter; Braczynski, Anne K.; Penski, Cornelia; Burger, Michael C.; Theurillat, Jean-Philippe; Steinbach, Joachim P.; Plate, Karl H.; Đikić, Ivan; Fulda, Simone; Brandts, Christian; Kögel, Donat; Behrends, Christian; Harter, Patrick N.; Mittelbronn, Michel

doi:10.18632/oncotarget.7910

Cited by 34 publications

(26 citation statements)

References 48 publications

(49 reference statements)

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“…Autophagy is shown to be enhanced in astrocytomas and LAMP‐2 is detected in perinecrotic areas in GBM suggesting micro‐environmental changes as key player in autophagy induction in HGG . Temozolomide resistance of lung cancer cells is regulated via LAMP‐2‐mediated autophagy, the LAMP‐2 gene serving as the target of miR‐487b‐5p .…”

Section: Discussionmentioning

confidence: 99%

LAMP‐1 gene is overexpressed in high grade glioma

Sarafian

Koev²,

Mehterov

et al. 2018

APMIS

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High-grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome-associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP-1 and LAMP-2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP-1 and LAMP-2. The transcriptional activity of LAMP-1 in HGG was significantly higher compared to normal brain and to LAMP-2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP-1 showing again enhanced expression. In conclusion, novel data on LAMP-1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.

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Section: Discussionmentioning

confidence: 99%

LAMP‐1 gene is overexpressed in high grade glioma

Sarafian

Koev²,

Mehterov

et al. 2018

APMIS

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show abstract

“…Autophagy is involved in tumorigenesis, and a blockade has been proposed as an alternative therapeutic option. Autophagy is reportedly enhanced in astrocytomas compared to that in normal brain tissue [34]. In our study, autophagy was a significantly enriched biological process according to bioinformatics analyses, and four candidate proteins were involved in this process, including cathepsin D, lysosome-associated membrane glycoprotein 1, lysosome-associated membrane glycoprotein 2 and annexin A7.…”

Section: Discussionmentioning

confidence: 54%

Candidate urine biomarker discovery from only five pairs of samples before and after tumor resection in glioma patients

Zhang

Zhao

et al. 2018

Preprint

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Biomarkers are measurable changes associated with the disease. Without the control of homeostatic mechanisms, urine accumulates systemic body changes and thus serves as an excellent early biomarker source. However, urine is affected by many factors other than disease. Although many candidate biomarkers have been identified in animal models, a large number of clinical samples might still be required for the disease related changes. A self-controlled study should be able to avoid the interferences of individual differences among patients. Gliomas are the most common primary malignant brain tumors and have a very poor prognosis. Early diagnosis of gliomas and the monitoring of tumor recurrence are crucial to improve glioma patient outcomes. Here we set to try if biomarker candidates can be identified by comparing urine samples from five glioma patients collected at the time of tumor diagnosis and after surgical removal of the tumor.Using label-free liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) quantification, twenty-seven urinary proteins were significantly changed after tumor resection (fold change ≥ 1.5, P-value < 0.05, and similar changes in all 5 patients), many of which have been previously associated with gliomas, such as CEACAM1, ANXA7, CALR, CRYAB, CD276, pIgR and cathepsin D. Functions of these proteins were significantly enriched in the regulation of tissue remodeling, autophagy, the inhibition of gene expression, the positive regulation of natural killer cell-mediated cytotoxicity and angiogenesis, which are associated with glioma development. Our results suggested that using the self-control of before and after tumor resection is an effective method to identify differential proteins associated with the disease, even with a small number of patients.

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“…After functional analysis of DEPs identified by LFQ, several important biological processes were significantly enriched, such as autophagy and angiogenesis. Autophagy is involved in tumorigenesis, and it is reportedly enhanced in glioma compared to normal brain tissue [21]. Moreover, blockade of autophagy has been proposed as an alternative therapeutic option for gliomas.…”

Section: Discussionmentioning

confidence: 99%

Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics

Zhang

Wei

et al. 2020

Chin Neurosurg Jl

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Background: Gliomas are the most common primary malignant brain tumors and have a poor prognosis. Early detection of gliomas is crucial to improve patient outcomes. Urine accumulates systematic body changes and thus serves as an excellent early biomarker source. Methods: At the biomarker discovery phase, we performed a self-controlled proteomics analysis by comparing urine samples collected from five glioma patients at the time of tumor diagnosis and after surgical removal of the tumor. At the biomarker validation phase, we further validated some promising proteins using parallel reaction monitoring (PRM)-based targeted proteomics in another cohort, including glioma, meningioma, and moyamoya disease patients as well as healthy controls. Results: Using label-free proteome quantitation (LFQ), we identified twenty-seven urinary proteins that were significantly changed after tumor resection, many of which have been previously associated with gliomas. The functions of these proteins were significantly enriched in the autophagy and angiogenesis, which are associated with glioma development. After targeted proteomics validation, we identified a biomarker panel (AACT, TSP4, MDHM, CALR, LEG1, and AHSG) with an area under the curve (AUC) value of 0.958 for the detection of gliomas. Interestingly, AACT, LEG1, and AHSG are also potential cerebrospinal fluid or blood biomarkers of gliomas. Conclusions: Using LFQ and PRM proteome quantification, we identified candidate urinary protein biomarkers with the potential to detect gliomas. This study will also provide clues for future biomarker studies involving brain diseases.

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Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas

Cited by 34 publications

References 48 publications

LAMP‐1 gene is overexpressed in high grade glioma

LAMP‐1 gene is overexpressed in high grade glioma

Candidate urine biomarker discovery from only five pairs of samples before and after tumor resection in glioma patients

Urinary biomarker discovery in gliomas using mass spectrometry-based clinical proteomics

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