AFAP1 and its naturally occurring antisense RNA are downregulated in gastric cancer samples

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 inva-sion 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.

Bioinformatic Prioritization and Functional Annotation of GWAS-Based Candidate Genes for Primary Open-Angle Glaucoma

“…ATP-binding cassette transporter A1 ( ABCA1 ) protein is a cholesterol and phospholipid transporter across the cell membrane, and mutation of this gene is associated with cancer and lipoprotein metabolism abnormality [ 79 , 80 ]. Although the association of AFAP1 and ABCA1 genes with cancer has been widely studied [ 81 , 82 ], there is a paucity of data showing the underlying mechanism in glaucoma. Cui et al used reverse transcription polymerase chain reaction and immunolabeling approaches to examine the expression of AFAP1, ABCA1, and GMDS in human ocular tissues.…”

A Review on the Role of AFAP1-AS1 in the Pathoetiology of Cancer

“…Except from a single low-sample size study in gastric cancer which reported down-regulation of AFAP1-AS1 in tumoral tissues versus nearby samples ( 6 ), other studies consistently reported over-expression of AFAP1-AS1 in different neoplastic tissues compared with non-neoplastic tissues of the same origin ( Table 3 ). Even in the mentioned study, levels of AFAP1-AS1 were higher in patients who showed lymphatic or vascular invasion in comparison with those without these properties ( 6 ).…”

“…Except from a single low-sample size study in gastric cancer which reported down-regulation of AFAP1-AS1 in tumoral tissues versus nearby samples ( 6 ), other studies consistently reported over-expression of AFAP1-AS1 in different neoplastic tissues compared with non-neoplastic tissues of the same origin ( Table 3 ). Even in the mentioned study, levels of AFAP1-AS1 were higher in patients who showed lymphatic or vascular invasion in comparison with those without these properties ( 6 ). Moreover, different statistical methods have been applied to assess correlations between expression level of AFAP1-AS1 and clinical outcomes, all of them reporting significant impact of up-regulation of this lncRNA on increasing malignant behaviors of tumors and decreasing patients’ survival.…”

“…Both AFAP1 and FAP1-AS1 participate in the carcinogenesis through modulation of related signaling pathways. AFAP1 has acknowledged roles in the pathogenesis of a number of cancers, namely breast ( 4 ) and prostate cancer ( 5 ), yet its expression has been found to decreased in gastric cancer samples ( 6 ). AFAP1-AS1 is mainly regarded as an oncogenic lncRNA ( 1 ).…”

Differential expression of long non-coding RNAs as diagnostic markers for lung cancer and other malignant tumors

“…LncRNAs such as AFAP1-AS1, ADAMTSP-AS2, and GAS5 with suppressed expression levels in lung cancer are rarely used as diagnostic markers for other malignant tumors. Esfandi et al [ 126 ] evaluated the clinical value of lncRNA AFAP1-AS1 in gastric cancer and confirmed that AFAP1-AS1 is down-regulated in gastric cancer compared to para-carcinoma tissues, and could therefore, be used as a diagnostic biomarker. Chen et al [ 127 ] evaluated the expression and diagnostic significance of the two new ceRNAs in esophageal squamous cell carcinoma (ESCC).…”