Department of Surgery, Huashan Hospital, Fudan University, Shanghai, China.
World J Surg Oncol. 2011 Dec 13;9:166. doi: 10.1186/1477-7819-9-166.
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.
Immunohistochemical (IHC) staining and real-time PCR for hPer2 were performed for 38 CRC cases.
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.
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.
最近的研究表明，生物钟节律的破坏是促进哺乳动物癌症发生和发展的肿瘤促进因素之一，但对于结直肠癌（CRC）中生物钟基因的分子变化知之甚少。因此，在这项研究中，研究了关键生物钟调节因子之一人 Period2（hPer2）在 CRC 中的表达变化及其与预后的相关性。
对 38 例 CRC 病例进行 hPer2 的免疫组织化学（IHC）染色和实时 PCR。
hPer2 的 IHC 分析检测到 38 例 CRC 组织中 81.6%（31/38）和 97.4%（37/38）的周围非癌组织存在阳性染色（P<0.05）。非癌组织中的大多数结直肠细胞呈均匀染色。相比之下，在配对的癌组织中，发现存在异质性模式，相当一部分癌细胞显示阴性或弱阳性 hPer2 染色。在超过 60%的病例（24/38）中，非癌细胞中 hPer2 的染色强度明显高于配对的癌组织。分化良好的癌细胞比分化不良的癌细胞更有可能维持 hPer2 的表达。此外，还检测到 hPer2 水平降低与患者年龄、组织学分级、TNM 分期和核增殖相关抗原：Ki67 的表达有关（P<0.05）。hPer2 的表达与 p53 或 C-erB-2 的表达无关。与 hPer2 蛋白表达相似，hPer2 的实时定量 RT-PCR 也显示 CRC 中 mRNA 表达降低。
这些结果表明 hPer2 在正常结直肠细胞功能中起作用，并且 hPer2 表达的潜在失调可能在 CRC 的发展、浸润和转移中起作用。
