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Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma
Yu Zhang1, Xiaoping Huang, Jun Qi
1State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China.
Abstract:
Androgen-induced proliferation shutoff gene AS3, also known as APRIN, is a growth inhibitory gene that is initially implicated in prostate cancer. This gene is required for androgen-dependent growth arrest and is a primary target for 1,25(OH)(2)D(3) and androgens. Allelic loss at AS3 locus has been linked to a variety of cancers. However, the correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma (ESCC) is not well established. In this study, the genomic and expression alterations of AS3 in ESCC and their clinical significance are evaluated. Loss of heterozygosity (LOH) analysis using an AS3 intragenic microsatellite marker D13S171 revealed 72% allelic loss at AS3 locus in ESCC, which is significantly correlated with higher pathological grade (P=0.042). RT-PCR examination showed that AS3 mRNA obviously decreased in 44% tumors and its down-regulation was correlated with the sex of patients (P=0.03). Furthermore, the correlation between genomic and expression alterations of AS3 gene was analyzed in 18 ESCC specimens, which indicated that the consistency between allelic loss and decreased mRNA expression of AS3 was relatively poor. The results of this study indicate that the aberrant expression of AS3 may be involved in the tumorigenesis of esophagus and is responsible for the male predominance of ESCC.
Insights
The AS3 gene, crucial for growth control, shows significant allelic loss and reduced expression in esophageal squamous cell carcinoma (ESCC), particularly in males, suggesting its role in ESCC development and male predominance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- AS3 (APRIN) is a growth inhibitory gene involved in androgen-dependent growth arrest, implicated in prostate cancer.
- Allelic loss at the AS3 locus is associated with various cancers, but its role in esophageal squamous cell carcinoma (ESCC) is unclear.
Purpose of the Study:
- To evaluate genomic and expression alterations of AS3 in ESCC.
- To determine the clinical significance of these AS3 alterations in ESCC.
Main Methods:
- Loss of heterozygosity (LOH) analysis using microsatellite marker D13S171.
- Reverse transcription-polymerase chain reaction (RT-PCR) for AS3 mRNA expression analysis.
- Correlation analysis between genomic alterations, mRNA expression, and clinical parameters.
Main Results:
- 72% allelic loss at the AS3 locus in ESCC, correlated with higher pathological grade (P=0.042).
- AS3 mRNA down-regulation observed in 44% of ESCC tumors, linked to patient sex (P=0.03).
- Poor consistency between allelic loss and decreased AS3 mRNA expression.
Conclusions:
- Aberrant AS3 expression may contribute to esophageal tumorigenesis.
- Altered AS3 expression could explain the male predominance observed in ESCC.