Expression of circadian clock gene human Period2 (hPer2) in human colorectal carcinoma

BACKGROUND Recent studies have shown that disruption of circadian rhythms is one of the tumor promoting factors which contribute to mammalian cancer development and progression, but very little is known about the molecular changes of circadian genes in colorectal carcinoma (CRC). Thus, in this study, changes in the expression of human Period2 (hPer2), one of the key circadian clock regulators, in CRC and its correlation with prognosis were investigated. METHODS Immunohistochemical (IHC) staining and real-time PCR for hPer2 were performed for 38 CRC cases. RESULTS IHC analysis detected positive staining for hPer2 in 81.6% (31/38) of CRC tissues and 97.4% (37/38) of surrounding non-cancerous tissues (P < 0.05). Most colorectal cells in non-cancerous tissues were homogeneously stained. In contrast, in the paired cancerous tissues, a heterogeneous pattern was found with a significant portion of cancer cells displaying negative or weak hPer2 staining. In over 60% cases (24/38), the staining for hPer2 was much stronger in non-cancerous cells than in the paired cancerous cells. Well-differentiated cancer cells are more likely to maintain hPer2 expression than poorly-differentiated ones. Furthermore, associations of decreased hPer2 levels with patients' age, histological grade, TNM stage and expression of nucleus proliferation related antigen: Ki67 were also detected (P < 0.05). Expression of hPer2 did not correlate with that of either p53 or C-erB-2. Similar to hPer2 protein expression, quantitative RT-PCR for hPer2 also showed decreased mRNA expression in CRC. CONCLUSION These results suggest a role for hPer2 in normal colorectal cell function and the potential deregulation of hPer2 expression in the development, invasion, and metastasis of CRC.