Expression Patterns of Cataract-Associated Crystallin Genes in Uveal Melanoma

Abstract

Cataracts are the number one cause of blindness worldwide. Cataracts occur when the lens of the eye becomes cloudy due to the accumulation of damaged crystallin proteins. When undamaged, crystallins allow the lens to maintain transparency, helping with clear vision. While the genetic basis of cataracts is well documented, there is little research on how the expression levels of cataract-causing genes might be modified in other ocular diseases such as in uveal melanoma. This study analyzes potential genetic correlations between uveal melanoma and cataract-causing genes.

We hypothesize that if uveal melanoma alters the lens environment, then patients with uveal melanoma will exhibit significantly different expression levels of crystallin genes associated with cataract formation.

Using 81 uveal melanoma patient cases sourced from The Cancer Genome Atlas (TCGA), we conducted a comparative genomic analysis by focusing on ten genes from the crystallin family and standardizing their expression levels. Expression levels of the crystallin genes CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, and CRYGS in all TCGA uveal melanoma cases were determined using the gene expression tool. After refining the dataset by removing outliers exceeding 1.5 times the interquartile range, the model achieved a statistically significant p-value. This value was found when testing correlations between uveal melanoma and cataract formation. 

These results supported a genetic correlation between uveal melanoma and cataract expression. Moving forward, more detailed analyses can be done for specific cataract genes (such as CRYBA) allowing for connections to be made about molecular interactions leading to specific expression levels.