Researchers working on new methods to translate genetic data into possible novel and targeted treatments for prostate cancer may have found a new pathway — and biomarker — indicative of this type of cancer, according to a study, titled “Differentially Expressed Genes and Signature Pathways of Human Prostate Cancer,” published in the journal PLOS ONE.
Prostate cancer is the second most diagnosed cancer among American men, with an estimated 220,000 or more new cases in 2015. The cancer tends to have multiple tumor sites within a patient’s prostate and each can be genetically different. “With the availability of patient genomic data, we can look deep inside a tumor to consider its genetic background and find more effective prostate cancer treatments,” Jennifer S. Myers, a graduate student in the Department of Chemistry and Biochemistry at Florida State University, said in a news release.
The expansion of genomic and proteomic technology and methodology has improved the characterization of tumor biology, driving the search for more accurate cancer biomarkers. Gene and protein expression differences between normal and malignant prostate tissues serve as a pool for putative diagnostic, prognostic, and risk stratification biomarkers.
However, scientists are challenged in pinpointing amid the data of over 20,000 genes the exact genetic changes that matter in cancer development, progression, and treatment.
Dr. Myers and her research colleagues were able to identify genetic changes in prostate cancer by observing altered signal pathways instead of individual genes. “Imagine trying to find a single altered gene among a haystack of more than 20,000 genes,” she said. “Now imagine doing this for the hundreds of thousands of men diagnosed with prostate cancer each year. The task is daunting.”
Genes work in concerted networks to exert their molecular effects, so changes in gene expression should be suggestive of altered pathways. “By looking for altered pathways, we’ve significantly increased the size of our target,” Dr. Myers said.
Indeed, the researchers found that alteration of the transforming growth factor-beta (TGF-b) signaling pathway and the regulation by the Ran protein of the mitotic spindle formation pathway were strongly associated with prostate cancer.
Although the role of transforming growth factor-beta signaling pathway has been long implicated in prostate cancer, Ran/mitotic spindle pathway and overexpression of the Ran protein in prostate cancer remains unclear. “The fact that we identified a well-studied pathway in prostate cancer gives us confidence in our method,” Dr. Myers said. “Our next steps will be to confirm the significance of the Ran/mitotic spindle pathway in prostate cancer.”