Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma

Abstract

BackgroundClear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry.MethodsWe studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed.ResultsAmong 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage.ConclusionsOur study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia

“…These data also reveal the oncogenic effect of PHF2 low expression in ALL. Our data are consistent with previous reports which indicate that PHF2 low expression is associated with poor outcomes in human cancer [1][2][4][5]7,16].…”

“…For example, JMJD3 is highly expressed in T-cell ALL (T-ALL) [12]; KDM5B is highly expressed in acute lymphoblastic leukemia (ALL) [13]; PHF8 promotes breast cancer oncogenesis and governs the response to retinoic acid in acute myeloid leukemia (AML) [14,15]; and PHF2 is downregulated in colon cancer [4,7] and breast cancer [2]. It is also reported that low PHF2 expression is associated with increased aggressiveness of the clear cell variant of renal cell carcinoma and is a poor prognostic factor [16]. Until now, however, there have been no reports about the PHF2 expression in leukemia patients and its roles in oncogenesis in ALL.…”

Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview

“…In breast cancer, PHF2 had been shown to be phosphorylated by PKA and to promote cAMP-induced mesenchymal-epithelial transition (MET) 179 . In Clear Cell Renal Cell Carcinoma (CCRCC), high expression of PHF2 is associated with longer survival and smaller tumor size 180 .…”

PHF2 histone demethylase prevents DNA damage and genome instability by controlling cell cycle progression of neural progenitors

“…Working with them, PHF2 regulates various differentiation processes (16)(17)(18). Alterations in PHF2 have been identified in several cancer types (19)(20)(21). In-terestingly, PHF2 mutations have been found in patients with autism spectrum disorder (ASD) (22)(23)(24).…”