RGD Reference Report - Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer. - Rat Genome Database

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Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer.

Authors: Chen, Zijian  Huang, Zenghong  Luo, Yanxin  Zou, Qi  Bai, Liangliang  Tang, Guannan  Wang, Xiaolin  Cao, Guangwen  Huang, Meijin  Xiang, Jun  Yu, Huichuan 
Citation: Chen Z, etal., J Transl Med. 2021 Feb 16;19(1):73. doi: 10.1186/s12967-021-02740-6.
RGD ID: 150520009
Pubmed: PMID:33593392   (View Abstract at PubMed)
PMCID: PMC7885252   (View Article at PubMed Central)
DOI: DOI:10.1186/s12967-021-02740-6   (Journal Full-text)

BACKGROUND: Neurotrophic tropomyosin receptor kinases (NTRKs) are a gene family function as oncogene or tumor suppressor gene in distinct cancers. We aimed to investigate the methylation and expression profiles and prognostic value of NTRKs gene in colorectal cancer (CRC).
METHODS: An analysis of DNA methylation and expression profiles in CRC patients was performed to explore the critical methylations within NTRKs genes. The methylation marker was validated in a retrospectively collected cohort of 229 CRC patients and tested in other tumor types from TCGA. DNA methylation status was determined by quantitative methylation-specific PCR (QMSP).
RESULTS: The profiles in six CRC cohorts showed that NTRKs gene promoter was more frequently methylated in CRC compared to normal mucosa, which was associated with suppressed gene expression. We identified a specific methylated region within NTRK3 promoter targeted by cg27034819 and cg11525479 that best predicted survival outcome in CRC. NTRK3 promoter methylation showed independently predictive value for survival outcome in the validation cohort (Pā€‰=ā€‰0.004, HR 2.688, 95% CI [1.355, 5.333]). Based on this, a nomogram predicting survival outcome was developed with a C-index of 0.705. Furthermore, the addition of NTRK3 promoter methylation improved the performance of currently-used prognostic model (AIC: 516.49 vs 513.91; LR: 39.06 vs 43.64, Pā€‰=ā€‰0.032). Finally, NTRK3 promoter methylation also predicted survival in other tumors, including pancreatic cancer, glioblastoma and stomach adenocarcinoma.
CONCLUSIONS: This study highlights the essential value of NTRK3 methylation in prognostic evaluation and the potential to improve current prognostic models in CRC and other tumors.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NTRK3Humancolorectal cancer disease_progressionIDA  RGD 
Ntrk3Ratcolorectal cancer disease_progressionISONTRK3 (Homo sapiens) RGD 
Ntrk3Mousecolorectal cancer disease_progressionISONTRK3 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ntrk3  (neurotrophic receptor tyrosine kinase 3)

Genes (Mus musculus)
Ntrk3  (neurotrophic tyrosine kinase, receptor, type 3)

Genes (Homo sapiens)
NTRK3  (neurotrophic receptor tyrosine kinase 3)

Additional Information