A team of scientists has established the relation of Intratumoral Sterol-27-Hydroxylase (CYP27A1) to vitamin D signaling and cholesterol synthesis. The team has also established the association of CYP27A1 with the lethal form of prostate cancer.
Research reveals that a higher amount of intratumoral cholesterol synthesis could lead to a poor prognosis with respect to prostate cancer. The enzyme sterol-27-hydroxylase (CYP27A1) that tends to be vitamin D-regulated, is known for converting cholesterol into 27-hydroxycholesterol. As such, it helps in lowering the overall cholesterol levels potentially. The team of researchers has analyzed that lower CYP27A1 expression tends to be associated with low vitamin D signaling, increased cholesterol synthesis, and a higher risk of developing lethal prostate cancer.
Methods Used for the Study
In around 404 patients having prostate cancer prospective, the team analyzed the intratumoral CYP27A1 expression. The team also studied that different proxies belonging to cholesterol synthesis with the help of transcriptome profiling, expression of the intratumoral vitamin D receptor protein, and pre-diagnostic plasma 25-hydroxyvitamin D. The given set of patients were assessed upon for mortality of prostate cancer and metastases.
Results of the Study
CYP27A1 expression was observed to be lower in the tumors having a higher level of Gleason grade as well as higher expression of enzymes related to cholesterol synthesis, including SQLE –the second rate-limiting enzyme. Lower CYP27A1 expression was linked with the higher risk of developing lethal prostate cancer in both the cohorts and independent of SQLE. The given association was reduced in action when additional adjustments for Gleason grade were made.
The study concludes that the lower CYP27A1 expression resulted in higher cholesterol synthesis along with the increased risks of developing lethal prostate cancer. The given observations by the researchers tend to further provide support to the hypothesis that accumulation of intratumoral cholesterol through the processes of decreased catabolism and increased synthesis tends to be a characteristic of lethal prostate cancer.