Method for improved hepatocellular cancer diagnosis

A method of diagnosing a hepatocellular mass comprising:

• (a) quantifying the levels of one or more specified MET, DHFR, MDR1, and ALDHA1 fragment peptides in a protein digest prepared from a tissue sample obtained from the liver of a patient and calculating the level of said one or more MET, DHFR, MDR1, and ALDHA1 peptides in said sample by selected reaction monitoring using mass spectrometry;
• (b) comparing the level of said one or more MET, DHFR, MDR1, and ALDHA1 fragment peptides to a pair of reference levels, wherein
• a MET fragment peptide is compared to a MET benign hepatocellular adenoma reference level and a MET pre-malignant dysplastic nodule or malignant carcinoma reference level,
• a DHFR fragment peptide is compared to a DHFR benign hepatocellular adenoma reference level and a DHFR pre-malignant dysplastic nodule or malignant carcinoma reference level,
• an MDR1 fragment peptide is compared to an MDR1 benign hepatocellular adenoma reference level and an MDR1 pre-malignant dysplastic nodule or malignant carcinoma reference level, and
• an ALDHA1 fragment peptide is compared to an ALDHA1 benign hepatocellular adenoma reference level and an ALDHA1 pre-malignant dysplastic nodule or malignant carcinoma reference level;
• (c) determining that the liver mass is a benign hepatocellular adenoma or a pre-malignant dysplastic nodule or malignant carcinoma, using the criteria wherein:
• a level of MDR1 fragment peptide lower than said MDR1 benign hepatocellular adenoma reference level indicates that the mass is a benign hepatocellular adenoma;
• a level of ALDHA1 fragment peptide lower than said ALDHA1 benign hepatocellular adenoma reference level indicates that the mass is a benign hepatocellular adenoma;
• a level of MDR1 fragment peptide higher than said MDR1 ALDHA1 pre-malignant dysplastic nodule or malignant carcinoma reference level indicates that the mass is a pre-malignant dysplastic nodule or malignant carcinoma reference;
• a level of ALDHA1 fragment peptide higher than said ALDHA1 pre-malignant dysplastic nodule or malignant carcinoma reference level indicates that the mass is a pre-malignant dysplastic nodule or malignant carcinoma reference;
• a level of MET fragment peptide higher than said MET benign hepatocellular adenoma reference level indicates that the mass is a benign hepatocellular adenoma;
• a level of DHFR fragment peptide higher than said DHFR benign hepatocellular adenoma reference level indicates that the mass is a benign hepatocellular adenoma;
• a level of MET fragment peptide lower than said MET pre-malignant dysplastic nodule or malignant carcinoma reference level indicates that the mass is a pre-malignant dysplastic nodule or malignant carcinoma reference;
• and
• a level of DHFR fragment peptide lower than said pre-malignant dysplastic nodule or malignant carcinoma reference level indicates that the mass is a pre-malignant dysplastic nodule or malignant carcinoma.