![]() ![]() How to get the tumour-originated proteins which could be released into the blood is an important issue in cancer biomarker discovery. But only secreted proteins with dysregulated abundance in blood have the potential for clinical application. Tissue-based proteomic studies have also been carried out for biomarker discovery ( Kikuchi et al, 2012). However, identification of low-abundance proteins in the blood remains a challenge due to the complexity of the blood proteome. Thus, new biomarkers are urgently needed, especially for AFP-negative HCC patients.Īs a kind of body fluid commonly used in the clinic, blood is an ideal source for biomarker discovery. However, the sensitivity of AFP is insufficient ( Daniele et al, 2004). The elevation of AFP is a risk factor for HCC and can be used to help define patients at risk. Alpha-fetoprotein (AFP) is recommended for HCC screening and surveillance by many guidelines from Asia such as the Asian Pacific Association for the Study of the Liver (APASL) ( Omata et al, 2010) and the Japan Society of Hepatology (JSH) (2010). ![]() Screening programs have improved the early detection of HCC ( Sherman, 2005), especially in high-incidence regions such as Asia ( Mittal and El-Serag, 2013). The mortality of HCC is high mainly due to the late diagnosis. Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Novel HCC candidate serum markers were found through in-depth proteomic analysis of TIF, which demonstrated the successful utility of TIF in cancer serum biomarker discovery. In addition, serum THBS2 was found to be a novel independent indicator for poor prognosis of HCC. And the combination of serum SPARC and THBS2 could also distinguish HCC patients from benign liver disease patients (AUC=0.93, sensitivity=80%, specificity=94%). The combination of serum SPARC and THBS2 could distinguish HCC (AUC=0.97, sensitivity=86%, specificity=100%) or AFP-negative HCC (AUC=0.95, sensitivity=91%, specificity=93%) from healthy controls. ELISA result showed that the serum levels of SPARC and THBS2 in HCC patients were both significantly higher than those in healthy controls. Two overexpressed extracellular matrix proteins, SPARC and thrombospondin-2 (THBS2) were selected for further validation. ![]() Among them, 232 proteins were significantly upregulated in HCC-TIF and 257 proteins down-regulated. Totally, 3629 proteins were identified and 3357 proteins were quantified in TIF samples. Two proteins were selected for ELISA validation in serum samples. Sixteen paired TIF samples from HCC tumour and adjacent non-tumour tissues were analysed by isobaric tags for relative and absolute quantitation (iTRAQ) method. As a proximal fluid between body fluids and intracellular fluid, tissue interstitial fluid (TIF) is a suitable source for serum biomarker discovery. New serum biomarkers for HCC screening are needed, especially for alpha-fetoprotein (AFP) negative patients. The blood plasma, though, is confined within the blood vessels.Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. In terms of composition, the interstitial fluid is similar to the blood plasma since the two continuously exchange substances across capillary walls. ![]() It provides a means of delivering materials to the cells, intercellular communication, and removal of metabolic waste. Its main function is to bathe and surround the cells of the body. It is composed of water, amino acids, sugars, fatty acids, coenzymes, hormones, neurotransmitters, salts, and cellular products. The interstitial fluid is the fluid that fills the spaces between cells. The interstitial fluid and the blood plasma are the major components of the extracellular fluid. cerebrospinal fluid, synovial fluid, aqueous humour, serous fluid, gut fluid, etc.). It is composed of blood plasm a, interstitial fluid, lymph and transcellular fluid (e.g. It makes up about 26% of the total body water composition in humans. The extracellular fluid pertains to all body fluid outside the cell(s). It bathes and surrounds the cells of the body, and provides a means of delivering materials to the cells, intercellular communication, and removal of metabolic waste. The fluid found in the intercellular spaces composed of water, amino acids, sugars, fatty acids, coenzymes, hormones, neurotransmitters, salts, and cellular products. ![]()
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