Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma.
Clin Transl Oncol
; 23(9): 1874-1884, 2021 Sep.
Article
in En
| MEDLINE
| ID: mdl-33811629
ABSTRACT
PURPOSE:
Molecular mechanisms of uveal melanoma development in association with high pigmentation are unclear. Tyrosinase Related Protein (TYRP1) is not only one of the important melanogenesis marker that contributes to melanin synthesis, but can also prevents the melanocyte death. The induction of melanogenesis leads to induction of HIF-1α which can affect the behavior of melanoma cells and its surrounding environment. The aim of our study was to determine the expression of TYRP1 and HIF-1α at the protein and RNA level and determine its prognostic significance.METHODS:
In the present study, the expression of TYRP1 and HIF-1α was investigated on 61 formalin-fixed paraffin-embedded choroidal melanoma samples by immunohistochemistry. Fresh 50 samples were validated by real-time PCR. Results were correlated with clinicopathological parameters and Kaplan-Meier was performed to determine the prognostic significance.RESULTS:
High immunoexpression of TYRP1 and HIF-1α was present in 61 and 54% of patients, respectively. Both TYRP1 and HIF-1α correlated well with high pigmentation and BAP1 (BRCA1 Associated Protein-1) loss (p < 0.05) at IHC level as well as transcriptional level. There was reduced metastatic free survival in patients with necrosis and this was statistically significant (p = 0.010).CONCLUSION:
Our findings indicate that TYRP1 can be used as a potential biomarker in the development of targeted therapy in UM. Further studies on melanogenesis markers associated with TYRP1 could provide us a better understanding in this field.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidoreductases
/
Uveal Neoplasms
/
Membrane Glycoproteins
/
Biomarkers, Tumor
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
Tumor Hypoxia
/
Melanoma
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
Clin Transl Oncol
Year:
2021
Document type:
Article
Affiliation country:
India