β-Klotho Gene Linked to Muscle Invasion and Poor PFS in Bladder Cancer

September 19, 2016
Dave Levitan
Dave Levitan

The gene known as β-Klotho (KLβ) appears to play an important role in tumor invasion and progression in patients with bladder cancer, and urine KLβ levels may act as a useful biomarker, according to a new study.

The gene known as β-Klotho (KLβ) appears to play an important role in tumor invasion and progression in patients with bladder cancer, and urine KLβ levels may act as a useful biomarker, according to a new study. The related gene α-Klotho (KLα), in contrast, was not associated with outcomes. The results of the study were published in Oncology Reports.

“T1 high-grade bladder cancer progresses to muscle-invasive bladder cancer [MIBC] at a rate of 25% to 50%,” wrote study authors led by Kiyohide Fujimoto, MD, of Nara Medical University in Nara, Japan. “There is an emerging need to discover novel biomarkers that can predict the progression of the cancer accurately and become a clinically available therapeutic target.”

The KLα gene is known as an anti-aging gene that may have antitumor effects in some malignancies. The role of KLβ, however, has been unclear. In the new study, the researchers analyzed tissue samples from 155 non-MIBC patients and 6 MIBC patients, and performed additional laboratory studies to determine the genes’ role in the course of the malignancy.

Patients with high expression of KLβ had significantly shorter progression-free survival (PFS) than those with low expression (P < .0001); there was no difference between high and low expression of KLα (P = .68). Recurrence-free survival was not different for either of the genes.

On a multivariate analysis, gender, tumor category or grade, carcinoma in situ, and lymphovascular invasion were not significant predictors of PFS. KLβ expression, however, was a significant predictor: high expression had a hazard ratio for progression of 6.9 (95% CI, 2.6–18; P < .001).

Tumors that had lymphovascular invasion showed higher KLβ expression levels (P < .0001). On in vitro tests, treatment of tumor cells with exogenous KLβ protein enhanced the proliferation and migration capabilities of the cells. “These findings suggest that KLβ is highly related to disease progression via enhanced tumor invasion through the vessel wall,” the authors wrote.

More generally, the authors hypothesize that KLα may act as a tumor suppressor in urothelial carcinoma of the bladder, while KLβ acts as a tumor promoter. “Urine KLβ level is a possible biomarker for distinguishing non-MIBC from MIBC,” they added.