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Hepatic somatostatin receptor 2 expression during premalignant stages of hepatocellular carcinoma
N M Abdel-Hamid1, O M Mohafez, S Zakaria
1Biochemistry Department, College of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt, nabilmohie@yahoo.com.
Abstract:
Growth and antigrowth hormones were occasionally investigated in hepatocarcinoma. Somatostatin regulates cell proliferation and inhibits the secretion of many growth factors engaged to tumors through a group of receptors, including somatostatin receptor type 2 (SSTR2). Caspase-3 is a transcription factor which is elevated in liver cancers. The most commonly approved marker for liver cancer is alpha fetoprotein (AFP), although it has no more than 65% sensitivity and specificity. Hepatocarcinoma is also mediated by oxidative stress. Four groups of mice were used in this work: a control group and another three groups (Gp 2, 3, and 4) used for induction of HCC with a single subnecrotic dose of diethylnitrosamine (DENA). Gp 2 was sacrificed on the last day after 8 weeks, Gp 3 after 16 weeks, and Gp 4 after 24 weeks. Both liver tissue SSR2 protein and mRNA, liver AFP, and caspase-3 mRNA expression, concomitant to tissue malondialdehyde (MDA), were significantly elevated with depressed reduced glutathione (GSH). The change was much more prominent and stage dependent for SSR2. These effects were supported by graded histological abnormalities. The study encourages the use of liver tissue SSR2 protein and mRNA as a reliable tumor marker for liver cancer rather than AFP which is always misleading during silent stages of hepatocarcinogenesis.
Insights
Somatostatin receptor type 2 (SSTR2) shows promise as a reliable biomarker for liver cancer, outperforming alpha fetoprotein (AFP). Elevated SSTR2 levels correlate with hepatocarcinogenesis progression.
Area of Science:
- Hepatocellular carcinoma (HCC) research
- Biomarker discovery
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a major global health concern.
- Current biomarkers like alpha fetoprotein (AFP) have limited sensitivity and specificity.
- Somatostatin receptor type 2 (SSTR2) and caspase-3 are implicated in liver cancer progression, alongside oxidative stress markers.
Purpose of the Study:
- To evaluate somatostatin receptor type 2 (SSTR2) as a potential tumor marker for hepatocarcinogenesis.
- To compare the efficacy of SSTR2 with alpha fetoprotein (AFP) in detecting liver cancer.
- To investigate the role of caspase-3 and oxidative stress in hepatocarcinogenesis.
Main Methods:
- Induction of hepatocellular carcinoma (HCC) in mice using diethylnitrosamine (DENA).
- Assessment of liver tissue SSTR2 protein and mRNA expression at 8, 16, and 24 weeks post-induction.
- Measurement of liver AFP, caspase-3 mRNA, malondialdehyde (MDA), and reduced glutathione (GSH) levels.
- Histopathological evaluation of liver tissues.
Main Results:
- Significantly elevated SSTR2 protein and mRNA, AFP, and caspase-3 mRNA were observed in HCC-induced mice.
- Increased malondialdehyde (MDA) and decreased reduced glutathione (GSH) indicated elevated oxidative stress.
- SSTR2 expression showed a prominent and stage-dependent increase, correlating with histological abnormalities.
- AFP levels were less reliable, particularly in the early stages of liver cancer.
Conclusions:
- Liver tissue SSTR2 protein and mRNA are reliable and sensitive biomarkers for hepatocarcinogenesis.
- SSTR2 demonstrates superior diagnostic potential compared to AFP for early and advanced liver cancer detection.
- The findings support the use of SSTR2 as a promising marker for monitoring liver cancer progression.
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