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PTCH1 是 Hedgehog 信号通路的受体,与结直肠癌的转移潜能相关。

PTCH1, a receptor of Hedgehog signaling pathway, is correlated with metastatic potential of colorectal cancer.

机构信息

Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, People's Republic of China.

出版信息

Ups J Med Sci. 2010 Aug;115(3):169-75. doi: 10.3109/03009731003668316.

Abstract

BACKGROUND

Approximately 90% of colorectal cancer (CRC) deaths arise from the metastatic dissemination of primary tumors. It is difficult to predict metastasis of colorectal cancer, especially for patients with the same pathological subtype and differentiation. AIMS. To identify biomarkers for predicting CRC metastasis.

PATIENTS AND METHODS

We collected 19 primary tumors of CRC with identical pathological subtype, differentiation, and comparable Dukes' stages from patients with matched age and gender but completely different prognosis. Patients were divided into one high-risk and one low-risk group for metastasis. The expression levels of SHH, PTCH1, and sFRP1, which are components of the Hedgehog signaling pathway, were determined by real-time reverse transcription polymerase chain reaction (RT-PCR). To investigate further the correlation between expression level of PTCH1 and metastatic potential of CRC cells, we compared the mRNA and protein levels of the PTCH1 gene in LoVo cells with high metastatic potential and in HT-29, SW480, and SW620 cells with low metastatic potential by RT-PCR and flow cytometry.

RESULTS

We found that tumor tissues in the high-risk group for metastasis expressed lower levels of PTCH1 mRNA than did those in the low-risk group. Similarly, mRNA and protein levels of PTCH1 were inversely correlated with the metastatic potential of CRC cell lines. Expression levels of SHH and sFRP1 genes did not differ between the two groups.

CONCLUSION

Our data suggest that PTCH1 might be a potential biomarker that could discriminate CRC with high from that with low metastatic risk.

摘要

背景

大约 90%的结直肠癌(CRC)死亡是由原发性肿瘤的转移扩散引起的。预测结直肠癌的转移是困难的,特别是对于具有相同病理亚型和分化的患者。目的:确定预测 CRC 转移的生物标志物。

患者和方法

我们从具有匹配年龄和性别但完全不同预后的患者中收集了 19 例具有相同病理亚型、分化和可比 Dukes 分期的 CRC 原发性肿瘤。患者被分为转移的高风险和低风险组。通过实时逆转录聚合酶链反应(RT-PCR)测定 Hedgehog 信号通路的组成部分 SHH、PTCH1 和 sFRP1 的表达水平。为了进一步研究 PTCH1 的表达水平与 CRC 细胞转移潜能之间的相关性,我们通过 RT-PCR 和流式细胞术比较了高转移潜能的 LoVo 细胞和低转移潜能的 HT-29、SW480 和 SW620 细胞中 PTCH1 基因的 mRNA 和蛋白水平。

结果

我们发现转移高风险组的肿瘤组织中 PTCH1 mRNA 的表达水平低于低风险组。同样,CRC 细胞系中 PTCH1 的 mRNA 和蛋白水平与转移潜能呈负相关。两组之间 SHH 和 sFRP1 基因的表达水平没有差异。

结论

我们的数据表明,PTCH1 可能是一种潜在的生物标志物,可区分具有高转移风险和低转移风险的 CRC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00fe/2939517/0bbd4621a4c3/UPS-0300-9734-115-169-g001.jpg

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