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By comparative proteome analysis we searched for characteristic alterations of human stomach adenocarcinoma tissue and paired surrounding normal tissue. Selected differential protein spots were identified with peptide mass fingerprinting based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and database searching. We identified protein alterations in 18 stomach cancer tissues compared with normal controls, comprising elevated levels of eight proteins, including 14-3-3 zeta, calcyclin, keratin, apolipoprotein A-1 precursor, proteasome activator complex subunit, nucleoside diphosphate kinase, nicotinamide N-methyltransferase, and pyridoxal kinase. Five proteins (CA11, prohibitin, peroxiredoxin 4, serum amyloid P component, and NADH-ubiquinone oxidoreductase 23 kDa subunit) were decreased. These data are valuable for identification of differentially expressed proteins involved in stomach cancer carcinogenesis, providing biomarker candidates to develop diagnostic and therapeutic tools.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and is a leading cause of death. To contribute to the development and improvement of molecular markers for diagnostics and prognostics and of therapeutic targets for the disease, we have largely expanded the currently available human liver tissue maps and studied the differential expression of proteins in normal and cancer tissues. Reference two-dimensional electrophoresis (2-DE) maps of human liver tumor tissue include labeled 2-DE images for total homogenate and soluble fraction separated on pH 3-10 gels, and also images for soluble fraction separated on pH 4-7 and pH 6-9 gels for a more detailed map. Proteins were separated in the first dimension by isoelectric focusing on immobilized pH gradient (IPG) strips, and by 7.5-17.5% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels in the second dimension. Protein identification was done by peptide mass fingerprinting with delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry (DE-MALDI-TOF-MS). In total, 212 protein spots (117 spots in pH 4-7 map and 95 spots in pH 6-9) corresponding to 127 different polypeptide chains were identified. In the next step, we analyzed the differential protein expression of liver tumor samples, to find out candidates for liver cancer-associated proteins. Matched pairs of tissues from 11 liver cancer patients were analyzed for their 2-DE profiles. Protein expression was comparatively analyzed by use of image analysis software. Proteins whose expression levels were different by more than three-fold in at least 30% (four) of the patients were further analyzed. Numbers of protein spots overexpressed or underexpressed in tumor tissues as compared with nontumorous regions were 9 and 28, respectively. Among these 37 spots, 1 overexpressed and 15 underexpressed spots, corresponding to 11 proteins, were identified. The physiological significance of the differential expressions is discussed.

Patients with a high preoperative TSH level and small thyroid volume are at high risk of developing hypothyroidism following hemithyroidectomy. Potential risk of postoperative hypothyroidism should be discussed with these patients when thyroid surgery is being considered for a diagnostic purpose.

PurposeThe present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer.Materials and MethodsWith various gastric tissues, we performed immunohistochemical staining for CD44v9.ResultsThe positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis.ConclusionThis study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.