The Association between Functional Polymorphisms of COX-2 and Serum PGE2 Level in ESCC Patients in North of Iran

Sheshpoli, Maryam Sadegh; Khajeniazie, Safoura; Khoshnia, Masoud; Behnampour, Nasser; Saeidi, Mohsen; Moradi, Abdolvahab

doi:10.5539/jmbr.v9n1p133

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“…This may be described by having a +8473 (TC/CC) SNP (into 3′-UTR COX2) in 44% of the samples, based on our previous project. 32 Researchers have previously described that miR-146a directly binds into 3′-UTR COX2 and downregulate COX2 expression and subsequently decreased prostaglandin level. However, the mutation in 3ʹ-UTR COX2 disrupts the miR-binding site somehow prevents the regulatory effect of miR146a on COX2.…”

Section: Figurementioning

confidence: 99%

<p>MicroRNA-146a as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma</p>

Poli

Khajeniazi

Behnampour³

et al. 2020

CMAR

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Background and Aims: MicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3ʹ-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression. Materials and Methods: We quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time-PCR. Statistical analyses were conducted using one-sample t-test. Receiveroperating characteristic (ROC) curve and Kaplan-Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman's rho analysis. Results: The results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions (P-value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls (P-value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, P-value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, P-value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, P-value=0.453). Survival analysis by Kaplan-Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span. Conclusion: COX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.

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Section: Figurementioning

confidence: 99%