UNIVERSITY PARK, Pa. — A team of medical researchers have taken a step in investigating whether a type of RNA found to be linked to cancers — called microRNAs — could one day be used as a more accurate screening test for prostate cancer.
The researchers said that out of the 733 microRNAs analyzed by the team, there were 10 microRNAs that had a statistically significant difference in expression between men with and without prostate cancer, said Alicia McDonald, assistant professor of public health sciences, Penn State Hershey College of Medicine. MicroRNAs are non-coding RNAs that regulate gene expression by targeting messenger RNAs, which are protein-coding genes.
Although the team initially did find associations between some types of microRNAs and prostate cancer, once further adjustments were done in the analysis, the relationship was no longer statistically significant.
"When you're doing multiple hypothesis testing, you have to adjust for those multiple tests," said McDonald. “We examined 733 microRNAs at once which needed to be adjusted for in the analysis. After we did the multiple comparison adjustments, we didn't find any microRNA that was significant. We did conduct sub-group analysis in which we looked to see whether the expression of these microRNAs differ between black and white men.”
When the researchers further analyzed the samples by race without adjusting for multiple tests, they found a microRNA — miR-671-3p — that was differentially expressed between black and white men with prostate cancer, with black men having a higher expression.
McDonald said this microRNA needs to be validated in a different cohort of men and future research may need to explore why this microRNA differs by race among men with prostate cancer.
"This would be important because black men are known to be at higher risk for prostate cancer compared to any other race," said McDonald. "And it's important to identify men who are at high risk, particularly black men, because they are also known to have poorer prostate cancer outcomes such as higher rates of metastasis or prostate cancer-related deaths."
Current prostate cancer screening techniques include a digital rectal exam and a serum-based test for elevated prostate-specific antigen levels (PSA). Both tests have limitations, according to McDonald.
"The one limitation with serum PSA is that when men have an elevated PSA level that doesn't necessarily mean they have prostate cancer," said McDonald. "As a result, there are men who have this elevated PSA and the doctor recommends a prostate biopsy. While these men wait for the test, of course, they have anxiety because they're worried they may have prostate cancer. In addition, there are some risks associated with having a prostate biopsy such as infection or bleeding of the prostate."
McDonald said that the initial lack of significance in their results, after additional adjustments in the analysis, does not necessarily rule out using microRNAs for use in prostate cancer detection. Researchers continue to develop new technology and techniques to pave the way to better detect microRNAs, in particular, in blood.
"We need to investigate these microRNAs further and use a bigger cohort," said McDonald.
Although much more research needs to be conducted, McDonald added that because microRNAs are involved in cancer processes, such as proliferation, differentiation and cell death, they could also lead to future treatments for prostate cancer by targeting microRNAs that influence these cancer processes.
McDonald also worked with Manish A. Vira, vice chair of urologic research, associate professor of urology, Zucker School of Medicine at Hofstra/Northwell; Jing Shen, associate scientist, Gertrude H. Sergievsky Center, Columbia University Medical Center; Martin Sanda, professor of urology and chair, department of urology, Emory University School of Medicine; Jay D. Raman, professor and chief of urology, and Jiangang Liao, professor of public health sciences, both of Penn State College of Medicine; Dattatraya Patil, biostatistician, Emory University Hospital; and Emanuela Taioli, director of the Institute for Translational Epidemiology, professor of population health science and policy and professor of Thoracic Surgery.