Journal of Proteomics & Bioinformatics
Open Access
ISSN: 0974-276X
ISSN: 0974-276X
S K Jain, Shabnam Malik, Maryam Ranjpour, Saima Wajid and Deepshikha Pande-Katare
A. T Still University, USA
Posters & Accepted Abstracts: J Proteomics Bioinform
Post Human Genome Project era has opened new vistas for understanding gene expression and initiated several specialized â��Omicsâ��. Proteomics, one of these â��Omicsâ�� is the analysis of total cellular proteins under different physiological and pathological conditions and is useful for discovery of novel biomarkers for prediction, diagnosis and monitoring the progression of cancers by analysis of total cellular and/or serum proteins. Specific biomarkers can also help in monitoring the efficacy of therapeutic intervention. Hepatocellular carcinoma (HCC) is one of the highly prevalent cancers having high morbidity and mortality associated with it. At present, the analysis of serum �±-fetoprotein levels is the most accepted diagnostic test for HCC. However, it has relatively low sensitivity and specificity and has limited use. Our group has been working on cancer proteomics with the aim to develop biomarkers for early detection of HCC. We have developed a novel animal model to study chemically induced liver cancer. The serum protein profiles at various stages of disease progression have been analyzed by 2D electrophoresis. A number of differentially expressed proteins have been detected, some of which bear direct correlation with disease progression. Histopathology and marker enzyme analyses have been used to confirm and monitor the initiation of tumors and disease progression. Few proteins of interest have been characterized by MALDI-TOF and LC-MS/MS. We report the analysis of two of these proteins. The levels the first protein are elevated during very early stage of cancer initiation and remain elevated thereafter. The cloning and high level expression of this protein has been achieved. The sequencing of its gene revealed presence of four, earlier unknown specific point mutations. The mutated protein shows immunogenicity and the diseased animals have circulating antibodies against it. The structure-function analysis provided important clues about the mechanistic aspect of these mutations. Sera of clinically confirmed HCC patients have elevated levels of this protein that supports its potential as probable biomarker for diagnosis of HCC. Another protein which is of great interest has multiple actions and shows biphasic response. It is elevated at the early stage and has a role in Tumor initiation. At later stage, it is highly down regulated. It acts as mediator of apoptosis which is down regulated at this stage. This in turn, promotes cancer progression. The real time PCR analysis of transcriptome reveals that the regulation of expression of this protein is at the transcriptional level. These findings are important in understanding the molecular mechanism of HCC development. The implications of these studies will be discussed.
Email: skjain@jamiahamdard.ac.in