Potential Role of Hsp70 and Activated NK Cells for Prediction of Prognosis in Glioblastoma Patients

Lobinger, Dominik; Gempt, Jens; Sievert, Wolfgang; Barz, Melanie; Schmitt, Sven; Nguyen, Huyen; Stangl, Stefan; Werner, Caroline; Wang, Fei; Wu, Zhiyuan; Fan, Hengyi; Zanth, Hannah; Shevtsov, Maxim; Pilz, Mathias; Riederer, Isabelle; Schwab, Melissa; Schlegel, Jürgen; Multhoff, Gabriele

doi:10.3389/fmolb.2021.669366

Cited by 18 publications

(23 citation statements)

References 58 publications

(78 reference statements)

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“…The chaperone Hsp70 have been found increased or decreased in human cancers by comparison with healthy control tissues [43][44][45]. An inverse correlation between Hsp70 levels and prognosis has been observed in some cancers [35,46]. In contrast to these findings, we did not detect a clear positivity reaction for Hsp70 in the GBM tissues we describe here, although we found low but still detectable levels of this chaperone in the commercially available stem line G166.…”

Section: Discussioncontrasting

confidence: 85%

The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications

Alberti¹,

Campanella²,

Paladino³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. Methods: Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry. Results: Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4. Conclusions: Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds.

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Section: Discussioncontrasting

confidence: 85%

The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications

Alberti¹,

Campanella²,

Paladino³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…The enigmatic and sophisticated association linking immunity with mitophagy are being gradually uncovered with the progress of the experimental research. One study from Paul K revealed that mitophagy could trigger the proliferation of CD8 + cell to improve prognosis in cancer [ 45 ]. Another study from Alejandro López-Soto suggested that the function of NK cell can be modulated by mitophagy [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a novel mitophagy-related gene prognostic signature for glioblastoma multiforme

Wang

Qiu²,

Huang

et al. 2022

BMC Cancer

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Background Glioblastoma multiforme (GBM) is one of the most malignant tumors in brain with high morbidity and mortality. Mitophagy plays a significant role in carcinogenesis, metastasis, and invasion. In our study, we aim to construct a mitophagy-related risk model to predict prognosis in GBM. Methods RNA-seq data combined with clinical information were downloaded from TCGA. The 4-gene risk model and nomograph was then constructed and validated in external cohort. Evaluation of immune infiltration, functional enrichment and tumor microenvironment (TME) were then performed. Result A mitophagy-related risk model was established and patients in TCGA and CGGA were classified into low-risk and high-risk groups. In both cohorts, patients in low-risk group had improved survival, while high-risk group had poor prognosis. Also, the risk model was identified as an independent factor for predicting overall survival via Cox regression. Furthermore, a prognostic nomogram including mitophagy signatures was established with excellent predictive performance. In addition, the risk model was closely associated with regulation of immune infiltration as well as TME. Conclusion In conclusion, our study constructed a mitophagy-related risk model, which can be utilized for the clinical prognostic prediction in GBM.

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“…The enigmatic and sophisticated association linking immunity with mitophagy are being gradually uncovered with the progress of the experimental research. One study from Paul K reveal that mitophagy trigger the proliferation of CD8 + cell to improve prognosis in cancer [45]. Another study from Alejandro López-Soto suggested that the function of NK cell can be modulated by mitophagy [46].…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Novel Mitophagy-Related Gene Prognostic Signature for Glioblastoma multiforme

Luo

wang

Qiu³

et al. 2022

Preprint

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Background: Glioblastoma multiforme (GBM) is one of the most malignant tumors in brain with high morbidity and mortality. Mitophagy plays a significant role in carcinogenesis, metastasis, and invasion. In our study, we aim to construct a mitophagy-related risk model to predict prognosis in GBM. Methods: RNA-seq data combined with clinical information were downloaded from TCGA. The 4-gene risk model and nomograph was then constructed and validated in external cohort. Evaluation of immune infiltration, functional enrichment and tumor microenvironment (TME) were then performed. Result: A mitophagy-related risk model was established and patients in TCGA and CGGA were classified into low-risk and high-risk groups. In both cohorts, patients in low-risk group had improved survival, while high-risk group have poor prognosis. Also, the risk model was identified as an independent factor for predicting overall survival via Cox regression. Furthermore, a prognostic nomogram including mitophagy signatures was established with excellent predictive performance. In addition, the risk model was closely associated with regulation of immune infiltration as well as TME. Conclusion: In conclusion, our study constructed a mitophagy-related risk model, which can be utilized for the clinical prognostic prediction in GBM.

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Potential Role of Hsp70 and Activated NK Cells for Prediction of Prognosis in Glioblastoma Patients

Cited by 18 publications

References 58 publications

The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications

The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications

Development and validation of a novel mitophagy-related gene prognostic signature for glioblastoma multiforme

Development and Validation of a Novel Mitophagy-Related Gene Prognostic Signature for Glioblastoma multiforme

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