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Posts Tagged ‘Birc3’


Author and Reporter: Ritu Saxena, Ph.D.

On June 4, 2012, I authored a post on HBV and HCV-associated Liver Cancer: Important Insights from the Genome https://pharmaceuticalintelligence.com/2012/06/04/hbv-and-hcv-associated-liver-cancer-important-insights-from-the-genome/ reporting about the major role of chromatin remodeling complexes and involvement of both interferon and oxidative stress pathways in hepatocellular malignant proliferation and transformation based on the genes showing recurrent mutations in the observed genes.

In this post, I have discussed the latest research on cyclin B1 and Sec62 expression in PBMCs of HCC patients and how their elevated expression correlates to significantly to negative prognostic value in terms of recurrence-free survival.

Researchers at the Changhai and Gongli Hospital in Shanghai, Military Medical University, People’s Republic of China recently identified the candidate biomarkers for HBV-related HCC recurrence after surgery. The research was published in the June 2012 issue of Molecular Cancer journal. According to the group findings, Cyclin B1 and Sec62 may serve as effective biomarkers and potential therapeutic targets for HBV-related HCC recurrence after surgery.

Research article: Identification of cyclin B1 and Sec62 as biomarkers for recurrence in patients with HBV-related hepatocellular carcinoma after surgical resection. http://www.ncbi.nlm.nih.gov/pubmed/22682366

HCC background and Research Problem: Hepatocellular carcinoma is cancer of the liver. It is different from Metastaticc liver cancer, which starts in another organ (such as the breast or colon) and spreads to the liver. The most frequent factors causing HCC include chronic viral hepatitis (types B and C), alcohol intake and afla- toxin exposure.

In most cases, scarring of the liver referred to as cirrhosis is an important risk factor for HCC. Cirrhosis may be caused by:

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001325/.

However, patients with hepatitis B or C are at risk for liver cancer, even if they have not developed cirrhosis.

According to the data from International Agency for Research on Cancer, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, with over a half million deaths per annum. http://www-dep.iarc.fr/

In China, a very high infection rates with HBV have been reported. According to the recent statistics reported by Jemal et al in 2011, HCC cases occurring in China account for 55% of the total cases reported in the world. http://www.ncbi.nlm.nih.gov/pubmed?term=Global%20Cancer%20Statistics%20Jemal

Surgical resection, although provides an opportunity for cure, however, frequent recurrence post surgery has posed a major challenge to longterm survival. Pertinent to their research, authors state “Frequent tumor recurrence after surgery is related to its poor prognosis. Although gene expression signatures have been associated with outcome, the molecular basis of HCC recurrence is not fully understood..”.

Research: To determine the molecular basis of HCC, authors used the Peripheral blood mononuclear cells (PBMCs) to predict the recurrence of HCC after surgery. Use of PBMCs was in contrast to previous studies that used just the liver tissues. PBMCs have the advantage of being easily obtained in the clinical setting. Thus, identification of biomarkers using PBMCs would be a great way to predict the recurrence of HCC post surgery.

A microarray-based gene expression profiling was performed to indentify candidate genes related to HCC recurrence. In all, mRNA derived from 6 HCC cases (3 cases with recurrence and 3 without recurrence) were subjected to genome-wide analysis. Some critical genes were indentified including cyclin B1 (CCNB1), SEC62 homolog (S. cerevisiae) (SEC62), and baculoviral IAP repeat-containing 3 (BIRC3), suggesting that they probably play important roles in the pathogenesis of HCC recurrence. To confirm the results of microarray analysis, the mRNA and protein expressions of these 3 genes were measured in 80 HCC samples from HCC cases and 30 samples from healthy cases. The authors found that the transcriptional and protein expressions of cyclin B1, Sec62, and Birc3 in the PBMCs were significantly higher in HCC samples than those in the non-recurrent and normal samples.

Furthermore, to determine the clinicopathologic significance of cyclin B1, Sec62, and Birc3 in HCC, immunohistochemical analysis from 35 recurrent tissues and 45 nonrecurrent revealed that the protein levels of cyclin B1, Sec62, and Birc3 were substantially higher in the recurrent tissues than those in the non-recurrent samples. Thus, the immunohistochemical results from tissues were consistent with the previous transcriptional and protein results in PBMCs.

Conclusion of study:  The authors discussed that “In recent years, studies on malignant tumors has primarily focused on cell proliferation, migration, and apoptosis. Cyclin B1, Sec62, and Birc3, chosen in this study according to our microarray analysis, likely play important roles in cell proliferation and migration. They can exert a tumor-promoting effect on HCC by regulating cell cycle and protein translocation.” As derived from the statistical methods employed in the research, elevated cyclin B1 and Sec62 expression in PBMCs had a significantly negative prognostic value in terms of recurrence-free survival, which hints the potential use of these molecular markers to predict the risk of tumor recurrence after surgery and to act as therapeutic targets to reduce tumor recurrence and improve clinical therapies.

Thus, these results revealed that cyclin B1 and Sec62 may be candidate biomarkers and potential therapeutic targets for HBV-related HCC recurrence after surgery.

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