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Abstract:  
Background: The type I inositol polyphosphate-5-phosphatase A (INPP5A) is involved in different cellular events such as cell proliferation. Since INPP5A, HLAG1, IL-10, and MMP-21 genes play fundamental roles in ESCC tumorigenesis, we aimed in the present study to clarify the possible interplay of these genes and explore its potential as a predictor marker for diagnostic in the disease. Methods: Gene expression analysis of INPP5A, HLAG-1, IL-10, and MMP-21 was performed using relative comparative real-time PCR in 56 ESCCs compared to their margin normal tissues. Immunohistochemical staining was accomplished for INPP5A in ESCCs. Analysis of receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC) were applied to evaluate the diagnostic capability of candidate genes. Results: High levels of HLA-G1, MMP-21, and IL-10 were detected in nearly 23.2%, 62.5%, 53.5% of ESCCs compared to the normal tissues, respectively, whereas INPP5A underexpression was detected in 19.6% of ESCCs, which all tested genes indicated significant correlations with each other. The protein expression levels of INPP5A in ESCC tissues were significantly lower than in the non-tumor esophageal tissues (P = 0.001). Interestingly, the concomitant expression of the INPP5A/HLA-G1, INPP5A/MMP-21, INPP5A/IL-10, HLA-G1/ MMP-21, HLA-G1/ IL-10, and MMP-21/ IL-10 was significantly correlated to several clinicopathological variables. INPP5A, HLA-G1, MMP-21, and IL-10 resulted in being the best candidates to discriminate tumor/non-tumor groups due to the total AUCs of all combinations (>60 %). Conclusion: Our observations highlight the role of the INPP5A/HLAG-1/IL-10/ MMP-21 axis in ESCC development. Notably, the results of ROC analysis imply that the combined detection of INPP5A, HLA-G1, IL-10, and MMP-21 might serve as promising predictors for diagnostic in ESCC patients with relatively high sensitivity and specificity.
     
Type of Study: Full Length | Subject: Cancer Biology

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