Hepatocellular carcinoma (HCC) is the most common type of liver cancer. This type of cancer has been observed with prevalence as the third leading cause of death from cancer worldwide and as the ninth leading cause of cancerous mortality in the United States. People with hepatitis B or C are considered to be at high risk for this kind of cancer. Remarkably poor prognostic HCC patients with low survival rates commonly possess intra-hepatic metastases that are either tumor thrombi in the portal vein or intra-hepatic spread. It is uncommon for them to die of extra-hepatic metastases. Therefore, identifying metastatic HCC has become vital and clinically challenging in efforts of timely therapeutic intervention to improve the survival rate of patients who suffer from this disease.
To date, studies that look for an accurate molecular profiling model have been developed to identify these patients in advance for a better treatment or intervention. An approach has been to focus on identifying individual candidate genes characterizing metastatic HCC. Another direction has been to find a global genome scale solution by using microarray technology to obtain a gene expression for this carcinoma. Among research following the latter was that developed by Qing-Hai Ye et al., Nature Medicine, Volume 9, Number 4, April 2003. They applied cDNA microarray-based gene expression profiling with compound co-variate predictors for primary HCC, metastatic HCC, and metastasis-free HCC binary classification tasks on a dataset of 87 observations and 9984 features taken from 40 hepatitis B-positive Chinese patients. Notably, a robust 153-gene model was generated to successfully classify tumor-thrombi-in-the-portal-vein samples with metastasis-free samples. However, they admitted distinguishing primary tumor samples from their matched-metastatic lesions were still a challenge. In this molecule signature, a gene named osteopontin, a secreted phosphoprotein, served as the lead gene in diagnosing HCC metastasis.
The analysis is based on the metastatic status of HCC, which is clinically predetermined. However, the validation of the class definition is needed to investigate if the data are sufficient to translate the three classes predefined. We will use some statistical clustering algorithms to validate the class defined. After that, we will conduct variable selection to find markers that are differentially expressed genes among clinical groups validated from this research. Next, using the compound markers found by this research, we will develop a statistical model to predict a new patient’s HCC type for intervention. The generalized performance of the prediction model will be evaluated via a cross-validation test. This study aims to build a highly accurate model that renders a better classification of the fore-mentioned clinical groups of HCC and thus enhances the rate of predicting metastatic patients.
|Commitee:||Suaray, Kagba, Zhou, Tianni|
|School:||California State University, Long Beach|
|Department:||Mathematics and Statistics|
|School Location:||United States -- California|
|Source:||MAI 58/02M(E), Masters Abstracts International|
|Subjects:||Biostatistics, Genetics, Bioinformatics, Artificial intelligence|
|Keywords:||Gene expression profile, Hepatocellular carcinoma, Machine learning, Statistical algorithms, Statistical genetics, Tissue classification|
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