Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ –MALDI-MS/MS

Abstract

Hepatocellular carcinoma(HCC) is serious condition associated with a high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (p<0.01), consistent with the iTRAQ results.The 14 proteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a possible association with HCC progression.

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

“…While miR-1 may play a role as a tumor suppressor gene in laryngeal carcinoma. Similarly, miR-200 is crucial for the maintenance of epithelial identity, behavior, and sensitivity to chemotherapy in ovarian cancer cell line (20,21), which confirmed our previous observation by miRNA microarrays with samples obtained from the same patients as this study (22). All these findings suggest that a functional relation is present between FN1 and platinum response, which supports our data in EOC.…”

Identification of key pathways and biomarkers in sorafenib‑resistant hepatocellular carcinoma using bioinformatics analysis

“…It participates in blood coagulation, inflammatory response, apoptosis regulation and the prevention process of metastasis in cancer cells (38,39). KNG1 is overexpressed in CRC and HCC (40) and is regarded as a potential prognostic marker for CRC, as patients with increased KNG1 expression exhibit decreased survival rates when compared with lower KNG1 expression patients (39,41). Additional studies reported that KNG1 may be involved in cholesterol and lipoprotein metabolism disturbance and take part in the complex interplay between the hemostatic system and immune response in hepatitis C virus (HCV)-associated HCC (39,40).…”

Comparative analysis of primary hepatocellular carcinoma with single and multiple lesions by iTRAQ-based quantitative proteomics

“…Particularly, the isobaric tags for relative and absolute quantitation (iTRAQ) profiling technology enables the quantitative and direct comparison of the proteome changes up to 8 samples simultaneously with very high sensitivity and protein coverage [21,22]. Several groups have reported the application of iTRAQ-based quantitative proteomics approach in the study of hepatic cancer, especially for the screening of diagnostic and prognostic protein biomarkers [23][24][25]. For instance, Huang et al have reported the iTRAQ-based quantitative analysis of the recurrence/metastasis of Huge HCC (diameter is larger than 10 cm) at different stages, and identified two biomarkers for distinguishing and predicting the early recurrence/metastasis behaviors of Huge HCC [26]; Wang et al have reported the serum proteome of metastatic HCC using the iTRAQ-based quantitative analysis and identified a metastasis-associated biomarker [27].…”