Genetic testing for high-grade osteosarcoma: a guide for future tailored treatments?

Hattinger, Claudia Maria; Patrizio, Maria Pia; Tavanti, Elisa; Luppi, Silvia; Magagnoli, Federica; Picci, Piero; Serra, Massimo

doi:10.1080/14737159.2018.1535903

Cited by 14 publications

(12 citation statements)

References 111 publications

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“…Predicting the prognosis of patients in osteosarcoma accurately is of important clinical value, which may be helpful for risk stratification and clinical decisionmaking and for guiding individual treatment. Up to now, the most widely used prognostic markers for osteosarcoma include tumor features such as the AJCC-TNM classification and clinical factors, including gender, age, and site (Hattinger et al, 2018). However, the sensitivity and accuracy of these factors in predicting the prognosis of patients with osteosarcoma are limited.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of a Zinc Finger Protein Gene–Based Signature with Regard to Prognosis and Tumor Immune Microenvironment in Osteosarcoma

2022

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Osteosarcoma is the most common malignant bone tumor that seriously threatens the lives of teenagers and children. Zinc finger (ZNF) protein genes encode the largest transcription factor family in the human genome. Aberrant expressions of ZNF protein genes widely occur in osteosarcoma, and these genes are therefore attractive biomarker candidates for prognosis prediction. In this study, we conducted a comprehensive analysis of ZNF protein genes in osteosarcoma and identified prognosis-related ZNF protein genes. Then, we constructed a prognostic signature based on seven prognosis-related ZNF protein genes and stratified patients into high- and low-risk groups. The seven genes included MKRN3, ZNF71, ZNF438, ZNF597, ATMIN, ZNF692, and ZNF525. After validation of the prognostic signature in internal and external cohorts, we constructed a nomogram including clinical features such as sex and age and the relative risk score based on the risk signature. Functional enrichment analysis of the risk-related differentially expressed genes revealed that the prognostic signature was closely associated with immune-related biological processes and signaling pathways. Moreover, we found significant differences between the high- and low-risk groups for the scores of diverse immune cell subpopulations, including CD8+ T cells, neutrophils, Th1 cells, and TILs. Regarding immune function, APC co-inhibition, HLA, inflammation promotion, para-inflammation, T-cell co-inhibition, and the type I IFN response were significantly different between the high- and low-risk groups. Of the seven ZNF protein genes, lower expressions of ATMIN, MKRN3, ZNF71, ZNF438, and ZNF597 were correlated with a high risk, while higher expressions of ZNF525 and ZNF692 were associated with a high risk. The Kaplan–Meier survival analysis suggested that lower expressions of ATMIN, ZNF438, and ZNF597 and the higher expression of ZNF692 were associated with worse overall survival in osteosarcoma. In conclusion, our ZNF protein gene–based signature was a novel and clinically useful prognostic biomarker for osteosarcoma patients.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of a Zinc Finger Protein Gene–Based Signature with Regard to Prognosis and Tumor Immune Microenvironment in Osteosarcoma

2022

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“…The majority of data collected so far in HGOS concerns microRNAs (miRNAs) and lncRNAs. For details please refer to recent reviews [45][46][47]. Although the expression patterns and clinical impact of miRNAs and lncRNAs in HGOS largely need to be confirmed and better defined, on the basis of the findings reported so far, it is possible to consider them as novel attractive candidate biomarkers for monitoring disease progression, predicting outcomes and as novel candidate therapeutic targets which might be taken into consideration for planning innovative strategies of therapeutic intervention.…”

Section: Epigeneticsmentioning

confidence: 99%

Genomics and Therapeutic Vulnerabilities of Primary Bone Tumors

Scotlandi

Hattinger

Pellegrini

et al. 2020

Cells

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Osteosarcoma, Ewing sarcoma and chondrosarcoma are rare diseases but the most common primary tumors of bone. The genes directly involved in the sarcomagenesis, tumor progression and treatment responsiveness are not completely defined for these tumors, and the powerful discovery of genetic analysis is highly warranted in the view of improving the therapy and cure of patients. The review summarizes recent advances concerning the molecular and genetic background of these three neoplasms and, of their most common variants, highlights the putative therapeutic targets and the clinical trials that are presently active, and notes the fundamental issues that remain unanswered. In the era of personalized medicine, the rarity of sarcomas may not be the major obstacle, provided that each patient is studied extensively according to a road map that combines emerging genomic and functional approaches toward the selection of novel therapeutic strategies.

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“…Osteosarcoma exhibits a complex karyotype with high genetic and chromosomal instability seen as multiple rearrangements across the genome, kataegis and chromothripsis [ 3 – 6 ]. The genetic markers identified have been associated with treatment response and prognosis, thus appearing as promising candidates for a translation to clinical practice [ 7 , 8 ]. However, the limited extent of recurrent profiles identified indicates that a substantial regulation of the transcriptional programs in osteosarcoma may rather be caused by epigenetic programs [ 9 – 13 ], providing novel avenues for cancer therapy [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

miR-486-5p expression is regulated by DNA methylation in osteosarcoma

et al. 2022

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Background Osteosarcoma is the most common primary malignant tumour of bone occurring in children and young adolescents and is characterised by complex genetic and epigenetic changes. The miRNA miR-486-5p has been shown to be downregulated in osteosarcoma and in cancer in general. Results To investigate if the mir-486 locus is epigenetically regulated, we integrated DNA methylation and miR-486-5p expression data using cohorts of osteosarcoma cell lines and patient samples. A CpG island in the promoter of the ANK1 host gene of mir-486 was shown to be highly methylated in osteosarcoma cell lines as determined by methylation-specific PCR and direct bisulfite sequencing. High methylation levels were seen for osteosarcoma patient samples, xenografts and cell lines based on quantitative methylation-specific PCR. 5-Aza-2′-deoxycytidine treatment of osteosarcoma cell lines caused induction of miR-486-5p and ANK1, indicating common epigenetic regulation in osteosarcoma cell lines. When overexpressed, miR-486-5p affected cell morphology. Conclusions miR-486-5p represents a highly cancer relevant, epigenetically regulated miRNA in osteosarcoma, and this knowledge contributes to the understanding of osteosarcoma biology.

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Genetic testing for high-grade osteosarcoma: a guide for future tailored treatments?

Cited by 14 publications

References 111 publications

Comprehensive Analysis of a Zinc Finger Protein Gene–Based Signature with Regard to Prognosis and Tumor Immune Microenvironment in Osteosarcoma

Comprehensive Analysis of a Zinc Finger Protein Gene–Based Signature with Regard to Prognosis and Tumor Immune Microenvironment in Osteosarcoma

Genomics and Therapeutic Vulnerabilities of Primary Bone Tumors

miR-486-5p expression is regulated by DNA methylation in osteosarcoma

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