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Updated: Mar 23, 2026
Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
Aberrant expression of Sonic hedgehog signaling in Peutz-Jeghers syndrome
Xiaoping Xu1, Juan Su2, Ran Li1
1Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Insights
Aberrant expression of SHH pathway molecules, including SHH, PTCH, and GLI1, was identified in Peutz-Jeghers polyps (PJPs). These molecules progressively increased from PJPs to colorectal cancer, suggesting a role in PJS polyp development.
Area of Science:
- Gastroenterology
- Molecular Biology
- Oncology
Background:
- The Sonic Hedgehog (SHH) signaling pathway is crucial for gastrointestinal development.
- SHH pathway dysregulation is implicated in various gastrointestinal neoplasms.
Purpose of the Study:
- To investigate the role of the SHH signaling pathway in Peutz-Jeghers Syndrome (PJS).
- To examine the expression of SHH, PTCH, and GLI1 in PJS-associated colorectal lesions.
Main Methods:
- Real-time PCR and immunohistochemistry were used to analyze gene and protein expression.
- Expression levels were compared between normal tissues and colorectal lesions (PJPs, adenomas, adenocarcinomas).
Main Results:
- SHH, PTCH, and GLI1 mRNA and protein expression were significantly elevated in PJPs compared to normal tissue.
- Expression levels increased progressively along the PJP-adenoma-adenocarcinoma sequence.
- Increased protein expression correlated positively with tumor grade, depth, and lymph node metastasis.
Conclusions:
- Aberrant expression of SHH pathway molecules is identified in PJS.
- These findings suggest a novel mechanism for the development of PJ polyps.
- The SHH pathway may represent a therapeutic target in PJS.
Abstract:
The SHH signaling pathway is critical for gastrointestinal development and organic patterning, and dysregulation of SHH pathway molecules has been detected in multiple gastrointestinal neoplasms. This study investigated the role of the SHH signaling pathway in PJS. Expression of SHH, PTCH, and GLI1 was examined by real-time PCR and immunohistochemistry in 20 normal tissues and 75 colorectal lesions (25 PJPs, 25 adenomas, and 25 adenocarcinomas). Expression of SHH, PTCH, and GLI1 mRNA was higher in PJPs than in normal tissue (P < .05) and gradually increased along the PJP-adenoma-adenocarcinoma sequence (P < .05). Immunostaining indicated that SHH expression was present in 60% of PJPs, 72% of adenomas, and 84% of carcinomas, whereas 68% of PJPs, 72% of adenomas, and 88% of carcinomas exhibited cytoplasmic expression of PTCH. Moreover, high GLI1 expression was detected in 56% of PJPs, 64% of adenomas, and 80% of carcinomas; and high nuclear expression of GLI1 was observed in 8 adenomas with atypia and 15 carcinomas. Increased SHH, PTCH, and GLI1 protein correlated positively with tumor grade (P = .012, P = .003, and P = .007, respectively), tumor depth (P = .024, P = .007, and P = .01), and lymph node metastasis (P = .05, P = .015, and P = .005). This study identified aberrant expression of SHH pathway molecules in PJS, and the findings may supply a novel mechanism for the development of PJ polyps.
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