biomarker

Biomarker

1p/19q co-deletion

Diagnostic biomarkers.

With the emergence of the molecular era and retreat of the histology epoch in malignant glioma, it is becoming increasingly necessary to research diagnostic/prognostic/therapeutic biomarkers and their related regulatory mechanisms.

While accumulating studies have investigated coding gene-associated biomarkers in malignant glioma, research on comprehensive coding and noncoding RNA-associated biomarkers is lacking. Furthermore, few studies have illustrated the crosstalk signalling pathways among these biomarkers and mechanisms in detail.

Huang et al. identified differentially expressed genes and Competing endogenous RNA (ceRNA) networks in malignant glioma and then constructed Cox/Lasso regression models to further identify the most valuable genes through stepwise refinement. Top-down comprehensive integrated analysis, including functional enrichment, SNV, immune infiltration, transcription factor binding site, and molecular docking analyses, further revealed the regulatory maps among these genes. The results revealed a novel and accurate model (AUC of 0.91 and C-index of 0.84 in the whole malignant gliomas, AUC of 0.90 and C-index of 0.86 in LGG, and AUC of 0.75 and C-index of 0.69 in Glioblastoma) that includes twelve ncRNAs, 1 miRNA and 6 coding genes. Stepwise logical reasoning based on top-down comprehensive integrated analysis and references revealed cross-talk signalling pathways among these genes that were correlated with the circadian rhythm, tumour immune microenvironment and cellular senescence pathways. In conclusion, our work reveals a novel model where the newly identified biomarkers may contribute to a precise diagnosis/prognosis and subclassification of malignant glioma, and the identified cross-talk signalling pathways would help to illustrate the noncoding RNA-associated epigenetic regulatory mechanisms of glioma tumorigenesis and aid in targeted therapy 1).

Since the introduction of integrated histological and molecular diagnoses by the 2016 World Health Organization (WHO) Classification of Tumors of the Nervous System, an increasing number of molecular markers have been found to have prognostic significance in infiltrating gliomas, many of which have now become incorporated as diagnostic criteria in the 2021 WHO Classification. This has increased the applicability of targeted-next generation sequencing in the diagnostic work-up of neuropathology specimens and in addition, raises the question of whether targeted sequencing can, in practice, reliably replace older, more traditional diagnostic methods such as immunohistochemistry and Fluorescence in situ hybridization. Slocum et al. demonstrated that the Oncomine Cancer Gene Mutation Panel v2 assay targeted-next generation sequencing panel for solid tumors is not only superior to IHC in detecting mutation in IDH1/2 and TP53 but can also predict 1p/19q co-deletion with high sensitivity and specificity relative to Fluorescence in situ hybridization by looking at average copy number of genes sequenced on 1p, 1q, 19p, and 19q. Along with detecting the same molecular data obtained from older methods, targeted-next generation sequencing with an RNA sequencing component provides additional information regarding the presence of RNA based alterations that have diagnostic significance and possible therapeutic implications. They advocate for expanded use of targeted-next generation sequencing over more traditional methods for the detection of important molecular alterations as a part of the standard diagnostic work up for CNS neoplasms 2)


Biomarker status now guides clinical decisions in some subtypes of gliomas, including anaplastic oligodendroglioma and glioblastoma in the elderly.

1p/19q co-deletion, O6 methylguanine DNA methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) 1/2 mutations – are known to have important diagnostic, prognostic and predictive roles in glioma treatment.

Long noncoding RNA are aberrantly expressed in gliomas and exert diverse functions.

They are associated with tumor size, WHO grade, and prognosis in glioma patients. lncRNAs could function as potential molecular biomarkers of the clinicopathology and prognosis of glioma 3).


1)
Huang Y, Gao X, Yang E, Yue K, Cao Y, Zhao B, Zhang H, Dai S, Zhang L, Luo P, Jiang X. Top-down stepwise refinement identifies coding and noncoding RNA-associated epigenetic regulatory maps in malignant glioma. J Cell Mol Med. 2022 Feb 22. doi: 10.1111/jcmm.17244. Epub ahead of print. PMID: 35194922.
2)
Slocum CC, Park HJ, Baek I, Catalano J, Wells MT, Liechty B, Mathew S, Song W, Solomon JP, Pisapia DJ. Towards a single-assay approach: a combined DNA/RNA sequencing panel eliminates diagnostic redundancy and detects clinically-relevant fusions in neuropathology. Acta Neuropathol Commun. 2022 Nov 17;10(1):167. doi: 10.1186/s40478-022-01466-w. PMID: 36397144; PMCID: PMC9670552.
3)
Zhou Q, Liu J, Quan J, Liu W, Tan H, Li W. lncRNAs as potential molecular biomarkers for the clinicopathology and prognosis of glioma: A systematic review and meta-analysis. Gene. 2018 May 16. pii: S0378-1119(18)30544-4. doi: 10.1016/j.gene.2018.05.054. [Epub ahead of print] Review. PubMed PMID: 29777909.
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  • Last modified: 2023/01/07 12:29
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