Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation

Abstract

Familial aggregation of hepatocellular carcinoma (HCC), the third leading cause of cancer death worldwide, has shown to be a common phenomenon. We investigated the association between the genetic background and HCC familial aggregation. Serum samples were collected from HCC family members and normal control family members for screening the differentially expressed protein peaks with the approach of surface-enhanced laser desorption ionization time-of-flight mass spectrometry. Potential genetically associated protein peaks were selected and further identified by matrix assisted laser desorption ionization-time of flight mass spectrometry. A panel of six protein peaks (m/z 6432. 94, 8478.35, 9381.91, 17284.67, 17418.34, and 18111.04) were speculated to reflect the genetic susceptibility of HCC familial aggregation. Three of them (m/z 6432.94, 8478.35, and 9381.91) were selected to identify as the candidate proteins. Nine identified proteins, including mostly apolipoprotein family (ApoA1, ApoA2, ApoC3, ApoE) and serum amyloid A protein (SAA), were found overexpressed in the multiple HCC cases family members. The comparative proteomic profiles have suggested that genetic factors ought to be taken into account for familial aggregation of HCC. (Cancer Sci 2012; 103: 1833-1838 H epatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers, and ranks the third cause of cancer related death in the world (9.2% of the total).(1,2) Among different geographical regions, large variation of morbidity and risk factors were observed, with the highest rate in Asian, and lowest rate in the US as well as Europe countries.(3,4) Hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and chronic exposure to aflatoxin play crucial roles in hepatocarcinogenesis among Asian people, while fatty liver disease and high consumption of alcohol are the dominant causes among low incidence regions.(5,6) The HCC incidence rate is remarkably high in China, accounting for approximately 55% of annual new cases in the world.(7) Particularly in Guangxi province of China, an endemic area of HBV infection, the HCC mortality has risen as the first cause of malignant cancer-relative death. (8) It is well-accepted that HBV infection constitutes the main etiological factor of HCC, while the process of hepatocarcinogenesis integrates multi-stages and multi-factors, including interactions of HBV, chemical carcinogen, and genetic susceptibility.(9) In addiction, the literature conveys that the lifetime risk of developing HCC for HBV infected individuals has been estimated to be 40%, (10) implying that a wide individual discrepancy exists in the HCC susceptibility, and that environmental factors alone are insufficient to fully address the familial aggregation of HCC. (11,12) We have observed that most HCC occurs obviously in clusters by geographical distribution or by family aggregation in Guangxi, China. Family aggregation of HCC has received researchers' attention for decades. Pedigree studies are frequently carried out to val...

Tracking the important role of JUNB in hepatocellular carcinoma by single‑cell sequencing analysis

“…By integrating differential expression analysis, ChIP-seq data and PPI networks, the present results suggested that the JunB proto-oncogene (JUNB) may serve an important role in the development and progression of HCC and the immune response. In addition, apolipoprotein A2 (APOA2), which encodes a genetically susceptible protein in HCC (19), was found to exhibit the same expression pattern as JUNB. The present results may contribute to the identification of novel therapeutic targets for the treatment of HCC patients.…”

Genome‐wide association analysis identifies a GLUL haplotype for familial hepatitis B virus‐related hepatocellular carcinoma

“…From this point of view, HCC can be classified by the patient's family history into familial and sporadic cases, with greater than 80% of HCC cases belonging to the latter. [13][14][15] Specifically, Shih et al performed an association analysis similar to the methods of GWAS but with a short coverage range of only 67 SNPs, of which they identified 2 associated haplotype blocks within 3 0 -phosphoadenosine 5 0 -phosphosulfate synthase 1 (PAPSS1), albeit with low significance (P7.5E-3). Individuals with a family history of HCC have an increased overall risk of developing HCC compared with those without a family history.…”

“…12 Previous familial HCC studies used methods including protein mass spectrometry, clinical and pathological characteristic association, and association analysis of a limited number of single-nucleotide polymorphisms (SNPs). [13][14][15] Specifically, Shih et al performed an association analysis similar to the methods of GWAS but with a short coverage range of only 67 SNPs, of which they identified 2 associated haplotype blocks within 3 0 -phosphoadenosine 5 0 -phosphosulfate synthase 1 (PAPSS1), albeit with low significance (P7.5E-3). 15 Therefore, to our knowledge, the specific genetic factors correlated with familial HCC have not yet been studied by GWAS, most likely due to the difficulty in collecting sufficient familial HCC cases.…”

Identification and Validation of Stage‐Associated Serum Biomarkers in Colorectal Cancer Using MS‐Based Procedures

“…Between the proteins identified in the discovery phase, there was a significant enrichment of proteins involved in the complement and coagulation activation cascades (C5, C8G, C1QC, C7, and C9), which were previously considered as biomarkers of different cancers, [17] and several apolipoproteins also reported as plasma biomarkers for different types of cancer and obesity-cancer association. [22] In contrast to these tumors, our results showed a clear decline of APOC3 associated to CRC progression, providing a significant statistical value for diagnosis. In addition, C-reactive protein (CRP), an inflammation-related protein, increased exponentially in the serum of late-stage patients.…”