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Published on: May 1, 2019
AFAP1 and its naturally occurring antisense RNA are downregulated in gastric cancer samples
Farbod Esfandi1, Mohammad Taheri2, Amir Namvar1
1Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran 19857-17443, Iran.
Abstract:
Actin filament-associated protein 1 (AFAP1) encodes a protein which is an SRC proto-oncogene, non-receptor tyrosine kinase binding partner. This protein alters actin filament integrity in reaction to cellular signals. A long non-coding RNA, namely AFAP1-antisense RNA 1 (AS1), is transcribed from the antisense strand of this gene and potentially regulates its expression. In the present study, the expression levels of these two genes were evaluated in 30 gastric cancer samples and adjacent non-cancerous tissues (ANCTs) to identify their importance in this type of human malignancy. These two genes were significantly downregulated in gastric tumor samples compared with ANCTs (expression ratio 0.26 and 0.36, P=0.001 and P=0.04 for AFAP1 and AFAP1-AS1, respectively). Relative expressions of these two genes were associated with the location of primary tumor, in that AFAP1 and AFAP1-AS1 were significantly downregulated in all cardia tumor types compared with their paired ANCTs (P=0.04 and P=0.001, respectively). There were indications of a significant association between the expression levels of AFAP1 and peritoneal invasion and smoking history (P=0.05). Additionally, a lower expression level of AFAP1 was detected in younger patients and in high grade tumor types compared with olders and low grade tumors respectively (P=0.01 and P=0.04, respectively) and significantly higher expression levels of AFAP1-AS1 in patients with lymphatic/vascular invasion compared with those without lymphatic/vascular invasion (P=0.01). Furthermore, significant pairwise correlations were identified between the transcript levels of these genes in tumoral tissues and ANCTs (P values<0.05). The diagnostic power of AFAP1 and AFAP1-AS1 in gastric cancer was calculated as area under the curve (AUC) 0.75 and 0.67, respectively. The combination of the transcript levels of these two genes significantly enhanced the diagnostic power compared with diagnostic power of each gene (AUC, 0.76; P<0.001). The present study demonstrates the dysregulation of AFAP1 and AFAP1-AS1 in gastric cancer tissues in association with the clinicopathological data of patients and demonstrates the potential of these genes as diagnostic biomarkers.
Insights
Actin filament-associated protein 1 (AFAP1) and its antisense RNA 1 (AS1) are downregulated in gastric cancer. Their combined analysis shows potential as diagnostic biomarkers for this malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Actin filament-associated protein 1 (AFAP1) is a binding partner of SRC proto-oncogene, a non-receptor tyrosine kinase.
- AFAP1 influences actin filament integrity in response to cellular signals.
- AFAP1-antisense RNA 1 (AS1) is a long non-coding RNA transcribed from the AFAP1 gene's antisense strand, potentially regulating its expression.
Purpose of the Study:
- To evaluate the expression levels of AFAP1 and AFAP1-AS1 in gastric cancer.
- To identify the clinical significance and diagnostic potential of AFAP1 and AFAP1-AS1 in gastric cancer.
Main Methods:
- Gene expression analysis of AFAP1 and AFAP1-AS1 in 30 gastric cancer tissues and adjacent non-cancerous tissues (ANCTs).
- Correlation analysis between gene expression and clinicopathological data (tumor location, peritoneal invasion, smoking history, patient age, tumor grade, lymphatic/vascular invasion).
- Assessment of diagnostic power using Area Under the Curve (AUC).
Main Results:
- Both AFAP1 and AFAP1-AS1 were significantly downregulated in gastric tumor samples compared to ANCTs (expression ratios 0.26 and 0.36, respectively).
- Downregulation was observed in cardia tumors, and AFAP1 expression correlated with peritoneal invasion and smoking history.
- Lower AFAP1 levels were associated with younger patients and higher tumor grades, while higher AFAP1-AS1 levels correlated with lymphatic/vascular invasion. The combined AUC was 0.76.
Conclusions:
- AFAP1 and AFAP1-AS1 are dysregulated in gastric cancer, with expression levels linked to various clinicopathological features.
- These genes exhibit potential as diagnostic biomarkers for gastric cancer, with combined analysis improving diagnostic accuracy.
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