Publications

Publications

Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients.

J Mol Med (Berl). 2016 Dec;94(12):1411-1422

Wang T, Abou-Ouf H, Hegazy SA, Alshalalfa M, Stoletov K, Lewis J, Donnelly B, Bismar TA

Abstract

Ankyrin G (ANK3) is a member of the Ankyrin family, which functions to provide cellular stability by anchoring the cytoskeleton to the plasma membrane. Deregulation of ANK3 expression has been observed in multiple human cancers but its mechanism remains unknown. ANK3 expression in relation to disease progression and patients’ outcome was investigated in two cohorts of prostate cancer (PCA). Mechanistic studies were carried out in vitro and in vivo using several PCA cell lines and the avian embryo model. Silencing ANK3 resulted in significant reduction of cell proliferation through an AR-independent mechanism. Decreased ANK3 expression delayed S phase to G2/M cell cycle transition and reduced the expression of cyclins A and B. However, cells with knocked-down ANK3 exhibited significant increase in cell invasion through an AR-dependent mechanism. Furthermore, we found that ANK3 is a regulator of AR protein stability. ANK3 knockdown also promoted cancer cell invasion and extravasations in vivo using the avian embryo model (p < 0.01). In human samples, ANK3 expression was dramatically upregulated in high grade intraepithelial neoplasia (HGPIN) and localized PCA (p < 0.0001). However, it was downregulated castration resistant stage (p < 0.0001) and showed inverse relation to Gleason score (p < 0.0001). In addition, increased expression of ANK3 in cancer tissues was correlated with better cancer-specific survival of PCA patients (p = 0.012).

KEY MESSAGE:

Silencing ANK3 results in significant reduction of cell proliferation through an AR-independent mechanism. ANK3 knockdown results in significant increase in cell invasion through an AR-dependent mechanism. ANK3 is a regulator of AR protein stability. ANK3 knockdown also promotes cancer cell invasion and extravasation in vivo using the avian embryo model.

PubMed

Physician in operating room

Prostate Cancer Risk Calculator for MRI-guided biopsy (PCRC-MRI)

Original Story Published in Folio Magazine
February 03, 2022 By Adrianna MacPherson

Risk calculator helps pinpoint which patients are suitable for MRI-guided prostate biopsies that improve on the current standard of care.

Adam Kinnaird, a surgeon and assistant professor in the Faculty of Medicine & Dentistry, and a member of both APCaRI and CRINA collaborated with colleagues at UCLA to develop a new risk calculator that could reduce the number of unnecessary and invasive biopsies for prostate cancer. Dr. Kinnaird explains that the tool is available online for free, requires only conventional clinical data paired with data from prostate MRI scans, and targets an unmet clinical need for prostate cancer patients.

The efficacy and accuracy of the calculator were calculated from a 10-year study Kinnaird led on 2,354 men undergoing MRI-guided prostate biopsy. The results, published in CUAJ on October 18th 2021,  showed that the simple, free calculator significantly helped improve patient selection for biopsies.

More than one million prostate biopsies are performed in North America every year, and prostate cancer is the most common type of internal cancer in North American men. However, as Kinnaird explained, these biopsies aren’t always necessary and they come with certain risks.

“Only about 25 to 30 percent of them may show some prostate cancer, and up to seven percent of men, after they’ve had a prostate biopsy, end up getting hospitalized within 30 days. And, there’s a four percent risk of what’s called post-biopsy sepsis, which can cause patients to end up in the ICU or may even prove fatal,” said Kinnaird. “Anything we can do before the biopsy to determine whether the patient really needs a biopsy is very important for patient care.”

The risk calculator, called the PCRC-MRI, is the first in North America developed to predict biopsy outcomes in North American men. The combination of the standard-of-care data with MRI data provides two critical benefits: it triages patients to determine whether they truly need the biopsy in the first place, and if they do, it improves the technique so clinicians are better able to find more clinically significant prostate cancer.

“We did a net benefit analysis using this calculator. The analysis showed that we could safely avoid 16 biopsies out of every 100 at a risk threshold of 20 percent. What that means is we could potentially be saving 16 men from having to undergo this invasive procedure that has serious potential side effects,” said Kinnaird.

Kinnaird noted that the MRI-guided prostate biopsy is already a major improvement on the current standard of care in Alberta, called a 12-core transrectal ultrasound-guided biopsy.

“It’s basically a blind biopsy. An ultrasound probe can see the prostate, it can see the outline, but it cannot see if there’s actually any prostate cancer in the prostate,” Kinnaird explained. “So what’s done is the urologist or radiologist performing the biopsy takes 12 random samples from the prostate and hopes that they detect prostate cancer if it’s there.”

While many of the patients in the study received MRI-guided prostate biopsies at the University of California, Los Angeles, the U of A recently obtained a device called the UroNAV that allows patients to receive the same type of biopsy and gives clinicians a new tool in their arsenal.

“It gives us something to aim at,” said Kinnaird. “We take what we’ve learned from the MRI being done on the patient and create a model of their prostate in the software. Then we can fuse it to the ultrasound being done in real-time. It’s been shown to improve the detection of clinically significant prostate cancer and to reduce the rate or risk of identifying clinically insignificant prostate cancer, which is prostate cancer that we would not want to treat and therefore not want to detect.”

For the clinical data component, the PCRC-MRI examines certain variables that have previously been identified as risk factors for harbouring prostate cancer, from family history to an abnormal digital rectal examination.

The next steps involve creating more calculators that provide clinicians with beneficial information that can help with selecting patients for these invasive biopsies. Kinnaird is now working on a risk calculator for patients under active surveillance, which would examine the likelihood of their low-risk prostate cancer becoming more aggressive.

The study was supported by funding from the U.S. National Cancer Institute and the UCLA Clinical and Translational Science Institute.

- Perrin Beatty