TY - JOUR ID - 90228 TI - Modulation of EphA7 and pEphA7 Protein Expression: Potential Biomarkers for Early Detection of Hepatocellular Carcinoma JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Priya, Shivani AU - Kma, Lakhon AD - Cancer & Radiation Countermeasures Unit, Department of Biochemistry, North-Eastern Hill University, Shillong-793022, India. Y1 - 2022 PY - 2022 VL - 23 IS - 8 SP - 2843 EP - 2850 KW - Hepatocellular carcinoma KW - Biomarker KW - diethylnitrosamine KW - EphA7 DO - 10.31557/APJCP.2022.23.8.2843 N2 - Background: Hepatocellular carcinoma (HCC) is one of the leading drivers of cancer-related mortality in the world. As a result, researchers are constantly looking for ways to optimize the screening and diagnosis of the said malignancy. Objective: To establish the mice model of hepatocellular carcinoma with the administration of a suitable dose of diethylnitrosamine (DEN) and examine the utility of EphA7 and pEphA7 as ideal diagnostic markers in HCC. Methods: Swiss Albino (BALB/c) mice of around 10-12 weeks old were exposed to a known hepatocarcinogen-diethylnitrosamine at a dose of 20 mg/kg body weight at weekly intervals for a period of 4, 8, 12, & 16 weeks. Blood was collected from mice of different experimental groups, and age-matched control and serum were separated from whole blood samples. The liver homogenate was prepared after completion of treatment, and the resulting supernatant was used for enzyme assays. A range of liver biomarker enzyme assays such as Gamma-glutamyl transpeptidase (GGT), Acetylcholine esterase (AChE), GPx activity and GSH level, Heme oxygenase-1 (HO-1), GPC3 and alpha-fetoprotein (AFP) level along with the expression of Caspase-3, EphA7 and pEphA7 were evaluated. Results: An elevation in body weight and relative liver weight across the treatment period (4, 8, 12, 16 weeks) was observed in DEN-treated mice. Significant differences in GGT levels between control and DEN treated mice were noted in the present study (P < 0.005). In the 16th week of the treatment period, a significant difference in AchE level was noted between the treated and control group (P < 0.001). However, there was no statistically significant difference in the levels of SGOT and SGPT levels between the control and DEN treated groups (P > 0.001). Lower GSH and GPx levels were demonstrated in the treated mice as compared to control over all the treatment period. Loss of Caspase-3 expression and significant differences in expression of HO-1 activity in treated vs. non-treated group of mice were observed. Significant differences in EphA7 and pEphA7 protein expression levels were noted in the DEN-treated vs. control groups across all the treatment periods (4 weeks: P < 0.05; 8 weeks: P < 0.05; 12 weeks:  P < 0.005; 16 weeks: P < 0.05). Conclusion: The present study indicated that EphA7 and phosphoEphA7 over-expression might contribute to the malignancy transition, invasion development, and metastasis of HCC. As a result, along with the known markers such as AFP and others, EphA7 and pEphA7 could be a very putative biomarkers of HCC, particularly at a very early stage of cancer development. UR - https://journal.waocp.org/article_90228.html L1 - https://journal.waocp.org/article_90228_c571d5e894d52aff5c03660be18e5b0e.pdf ER -