Altered expression of the clock gene machinery in kidney cancer patients

Background and aimKidney cancer is associated with alteration in the pathways regulated by von Hippel-Lindau protein and hypoxia inducible factor α. Tight interrelationships have been evidenced between hypoxia response pathways and circadian pathways. The dysregulation of the circadian clock circuitry is involved in carcinogenesis. The aim of our study was to evaluate the clock gene machinery in kidney cancer.MethodsmRNA expression levels of the clock genes ARNTL1, ARNTL2, CLOCK, PER1, PER2, PER3, CRY1, CRY2, TIMELESS, TIPIN and CSNK1E and of the clock controlled gene SERPINE1 were evaluated by DNA microarray assays and by qRT-PCR in primary tumor and matched nontumorous tissue collected from a cohort of 11 consecutive kidney cancer patients.ResultsIn kidney tumor tissue, we found down-regulation of PER2 (median = 0.658, Q1–Q3 = 0.562–0.744, P < 0.01), TIMELESS (median = 0.705, Q1–Q3 = 0.299–1.330, P = 0.04) and TIPIN (median = 0.556, Q1–Q3 = 0.385–1.945, P = 0.01), up-regulation of SERPINE1 (median = 1.628, Q1–Q3 = 0.339–4.071, P = 0.04), whereas the expression of ARNTL2 (median = 0.605, Q1–Q3 = 0.318–1.738, P = 0.74) and CSNK1E (median = 0.927, Q1–Q3 = 0.612–2.321, P = 0.33) did not differ. A statistically significant correlation was evidenced between mRNA levels of PER2 and CSNKIE (r = 0.791, P < 0.01), PER2 and TIPIN (r = 0.729, P = 0.01), PER2 and SERPINE1 (r = 0.704, P = 0.01), TIMELESS and TIPIN (r = 0.605, P = 0.04), TIMELESS and CSNKIE (r = 0.637, P = 0.03), TIPIN and CSNKIE (r = 0.940, P < 0.01).ConclusionIn kidney cancer, the circadian clock circuitry is deregulated and the altered expression of the clock genes might be involved in disease onset and progression.