Identification Of Tumor-related Proteins For The Detection Of Liver And Pancreatic Cancer Using Several Proteomic Strategies

Liver is an important organ in human being which can carry out a multitude of biochemical reactions and play central roles on metabolism, energy conversion and regulation of immune response. Several infectious agents, chemical carcinogens and genetics factors contributed to the tumorigenesis of liver cancer, such as hepatocellular carcinoma (HCC). The five-year survival rate of HCC was less than 10% due to failure of early diagnosis. Alpha-fetoprotein (AFP) is only an available serologic biomarker for HCC diagnosis, however, about one third of HCC patients present with low levels of serum AFP in which some of the patients were in early stage. Therefore, discovery of additional biomarkers may improve early diagnosis of HCC as well as better understanding the mechanisms underlying tumorigenesis at the clinic. This study quantitatively compared the protein profiles between normal liver and several liver cancer cells corresponding to different AFP expression characteristics. Finally, 166 differentially expressed proteins were identified and five candidates were further verified at histological and serological levels, showing Annexin A2 and Tissue transglutaminase 2 (TGM2) could be served as potential biomarkers of HCC in serum. Meanwhile, we participated in human liver proteome project (HLPP) and involved in makes standard operating procedures for donor screening, sample collection and deciphering the related proteins of bile acid and bilirubin metabolism in the human liver proteome (HLP) dataset. Combined with the results of several experiments, we think the expression profile of HLP is the most comprehensive proteome dataset in human liver, reflecting the metabolic and physiological characteristics of healthy liver at the fasting condition. It gave important references and comparisons to liver diseases even hepatocelluar carcinoma.Pancreatic cancer was one of the most malignant digestive cancers worldwide. Because it was difficult to diagnose at an early stage and lacks of specific symptoms, its 5-year survival rate was less than 5%. CA19-9 was a common used biomarker of pancreatic cancer, but its diagnostic value was limited due to its poor sensitivity and specificity. Therefore, there is an urgent need to identify potential biomarkers for early diagnosis. Conditioned medium of pancreatic cancer and the adjacent normal pancreas organ cultures were collected and the tumor-related secretory proteins were enriched. Finally, 150 and 533 dissociative proteins were identified using thriple replicate shotgun LC-MS/MS strategy. The bioinformatics analysis revealed that about 35% and 43% proteins were localized to extracellular region and plasma membrane. Proteins which were involved in cell growth, immune and stress response might play important roles on the tumorigenesis of pancreatic cancer. This pancreatic cancer-related dissociative protein profile was helpful to search for potential biomarkers for early diagnosis of pancreatic cancer as well as better understand the mechanisms underlying tumorigenesis.