MYCN RNA levels determined by quantitative in situ hybridization is better than MYCN gene dosages in predicting the prognosis of neuroblastoma patients

Chang, Hsiu-Hao; Tseng, Yu‐Fen; Lu, Meng‐Yao; Yang, Yung‐Li; Chou, Shu‐Wei; Lin, Dong‐Tsamn; Lin, Kai‐Hsin; Jou, Shiann-Tarng; Hsu, Wen Ming; Jeng, Yung‐Ming

doi:10.1038/s41379-019-0410-x

Cited by 15 publications

(17 citation statements)

References 33 publications

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“…Patients with MYCN FISH + tumors would be classified into a higher risk group and given a higher dose of chemotherapy (Table S 3 ). An ultrasensitive quantitative RNA in situ hybridization technique, RNA scope, is emerging [ 32 ]. This method investigates MYCN amplification status at the RNA level.…”

Section: Discussionmentioning

confidence: 99%

MYCN protein stability is a better prognostic indicator in neuroblastoma

et al. 2022

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Objective MYCN oncogene amplification is associated with treatment failure and poor prognosis in neuroblastoma. To date, most detection methods of MYCN focus on DNA copy numbers instead of protein expression, which is the real one performing biological function, for poor antibodies. The current investigation was to explore a fast and reliable way to detect MYCN protein expression and evaluate its performance in predicting prognosis. Methods Several MYCN antibodies were used to detect MYCN protein expression by immunohistochemistry (IHC), and one was chosen for further study. We correlated the IHC results of MYCN from 53 patients with MYCN fluorescence in situ hybridization (FISH) and identified the sensitivity and specificity of IHC. The relationship between patient prognosis and MYCN protein expression was detected from this foundation. Results MYCN amplification status detected by FISH was most valuable for INSS stage 3 patients. In the cohort of 53 samples, IHC test demonstrated 80.0–85.7% concordance with FISH results. Further analyzing those cases with inconsistent results, we found that patients with MYCN amplification but low protein expression tumors always had a favorable prognosis. In contrast, if patients with MYCN non-amplified tumors were positive for MYCN protein, they had a poor prognosis. Conclusion MYCN protein level is better than MYCN amplification status in predicting the prognosis of neuroblastoma patients. Joint of FISH and IHC could confirm MYCN protein stability and achieve better prediction effect than the singular method.

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Section: Discussionmentioning

confidence: 99%

MYCN protein stability is a better prognostic indicator in neuroblastoma

et al. 2022

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“…For example, patients with older age at diagnosis (>18 months), independent from the stage, usually had a worse prognosis. 45 - 47 Moreover, MYCN status is associated with therapeutic response to immunotherapy. MYC and MYCN were found to regulate the expression of PD-L1 in neuroblastoma, 48 and MYCN could further inhibit NK cell activation in high-risk neuroblastoma.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Validation of a Prognostic Immune Signature in Neuroblastoma

Zeng

Xia

et al. 2021

Cancer Control

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Background Neuroblastoma (NBL) is the most common extracranial solid tumor in childhood, and patients with high-risk neuroblastoma had a relatively poor prognosis despite multimodal treatment. To improve immunotherapy efficacy in neuroblastoma, systematic profiling of the immune landscape in neuroblastoma is an urgent need. Methods RNA-seq and according clinical information of neuroblastoma were downloaded from the TARGET database and GEO database (GSE62564). With an immune-related-gene set obtained from the ImmPort database, Immune-related Prognostic Gene Pairs for Neuroblastoma (IPGPN) for overall survival (OS) were established with the TARGET-NBL cohort and then verified with the GEO-NBL cohort. Immune cell infiltration analysis was subsequently performed. The integrated model was established with IPGPN and clinicopathological parameters. Immune cell infiltration was analyzed with the XCELL algorithm. Functional enrichment analysis was performed with clusterProfiler package in R. Results Immune-related Prognostic Gene Pairs for Neuroblastoma was successfully established with seven immune-related gene pairs (IGPs) involving 13 unique genes in the training cohort. In the training cohort, IPGPN successfully stratified neuroblastoma patients into a high and low immune-risk groups with different OS (HR=3.92, P = 2 × 10−8) and event-free survival (HR=3.66, P=2 × 10−8). ROC curve analysis confirmed its predictive power. Consistently, high IPGPN also predicted worse OS (HR=1.84, P = .002) and EFS in validation cohort (HR=1.38, P = .06) Moreover, higher activated dendritic cells, M1 macrophage, Th1 CD4+, and Th2 CD4+ T cell enrichment were evident in low immune-risk group. Further integrating IPGPN with age and stage demonstrated improved predictive performance than IPGPN alone. Conclusion Herein, we presented an immune landscape with IPGPN for prognosis prediction in neuroblastoma, which complements the present understanding of the immune signature in neuroblastoma.

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“…Neuroblastomas with enhanced expression of N-MYC without MYCN amplification are known to be similarly high-risk and poor prognosis ( 43 ). Recent studies show that high N-MYC protein and RNA levels could be better biomarkers than MYCN gene amplification in predicting the prognosis of neuroblastoma patients ( 44 , 45 ), underscoring the importance of aberrant expression of N-MYC in tumor progression. Here, we discuss mechanisms of MYCN dysregulation at DNA, mRNA and protein levels, and corresponding therapeutic targets.…”

Section: Molecular Mechanisms Of Mycn Dysregulatiomentioning

confidence: 99%

“…Although the amplified genes tend to overexpress, gene amplification not necessarily leads to high level of gene expression. In fact, there is inconsistency between MYCN gene dosage, mRNA and protein levels, and clinical outcomes ( 44 , 63 ). For example, low DNA dosage but high RNA level is detected in some neuroblastoma samples, while high DNA dosage but low RNA level in some other samples ( 45 ).…”

Section: Gene Amplification Of Mycnmentioning

confidence: 99%

Molecular Mechanisms of MYCN Dysregulation in Cancers

et al. 2021

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MYCN, a member of MYC proto-oncogene family, encodes a basic helix-loop-helix transcription factor N-MYC. Abnormal expression of N-MYC is correlated with high-risk cancers and poor prognosis. Initially identified as an amplified oncogene in neuroblastoma in 1983, the oncogenic effect of N-MYC is expanded to multiple neuronal and nonneuronal tumors. Direct targeting N-MYC remains challenge due to its “undruggable” features. Therefore, alternative therapeutic approaches for targeting MYCN-driven tumors have been focused on the disruption of transcription, translation, protein stability as well as synthetic lethality of MYCN. In this review, we summarize the latest advances in understanding the molecular mechanisms of MYCN dysregulation in cancers.

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MYCN RNA levels determined by quantitative in situ hybridization is better than MYCN gene dosages in predicting the prognosis of neuroblastoma patients

Cited by 15 publications

References 33 publications

MYCN protein stability is a better prognostic indicator in neuroblastoma

MYCN protein stability is a better prognostic indicator in neuroblastoma

Establishment and Validation of a Prognostic Immune Signature in Neuroblastoma

Molecular Mechanisms of MYCN Dysregulation in Cancers

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