Identification and analysis of tumour-associated antigens in hepatocellular carcinoma

Yy, Shi; Wang, Hao-Chien; Yh, Yin; Ws, Sun; Y, Li; Cq, Zhang; Wang, Y; Wang, S; Wf, Chen

doi:10.1038/sj.bjc.6602460

Cited by 84 publications

(71 citation statements)

References 40 publications

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“…Consistent with recent studies demonstrating overexpression of PcG genes in cancer (Vonlanthen et al, 2001;Sellers and Loda, 2002;Kleer et al, 2003;Raaphorst et al, 2003;Breuer et al, 2004;Kim et al, 2004;Shi et al, 2005), we found that both BMI-1 and EZH2 are strongly expressed by a variety of tumours (Table 3; Supplementary Material; Figure 1). This broad upregulation in cancer makes them attractive immunotherapeutic targets for malignant disease.…”

Section: Discussionsupporting

confidence: 91%

“…Several recent studies suggest that they also contribute to the development of cancer in humans. Aberrant PcG protein expression, such as overexpression, failure of downregulation or coexpression, has been reported in Hodgkin's lymphoma , B-cell lymphoma , mantle cell lymphoma (Bea et al, 2001;Visser et al, 2001), prostate cancer (Sellers and Loda, 2002;Varambally et al, 2002), breast carcinoma (Kleer et al, 2003;Raaphorst et al, 2003;Kim et al, 2004), HCC (Shi et al, 2005) and during lung carcinogenesis (Vonlanthen et al, 2001;Breuer et al, 2004). Some of these altered patterns of expression may be of diagnostic and prognostic relevance (Varambally et al, 2002;Raaphorst et al, 2003;Breuer et al, 2004;Kim et al, 2004).…”

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confidence: 99%

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The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens

Steele

Torr

Noakes³

et al. 2006

Br J Cancer

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We used SEREX technology to identify novel tumour-associated antigens in patients with primary hepatocellular carcinoma and found serological responses to the polycomb group (PcG) protein BMI-1, which is overexpressed in a range of different tumour types. Further studies identified T-cell responses to both BMI-1 and another PcG protein, EZH2, in cancer patients and at relatively lower levels in some normal donors. We next identified several CD8 þ T-cell epitopes derived from BMI-1 and EZH2 and demonstrated that EZH2-derived peptides elicited more significant interferon-g (IFN-g) release than BMI-1-derived peptides. That CD8 þ T cells were responsible for the observed responses was confirmed for EZH2 by both IFN-g capture assays and tetramer staining using an HLA-A0201-restricted, EZH2-derived YMSCSFLFNL (aa 666 -674) epitope. The ability of YMSCSFLFNL (aa 666 -674) to stimulate the in vitro expansion of specific T cells from peripheral blood lymphocytes was greatly enhanced when the CD25 þ T-cell population was depleted. EZH2-specific cytotoxic T lymphocyte clones specific for two HLA-A0201 epitopes were generated and found to recognise endogenously processed EZH2 in both HLA-matched fibroblasts and tumour cell lines. Given the widespread overexpression of PcG proteins in cancer and their critical role in oncogenesis, these data suggest that they may be useful targets for cancer immunotherapy.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens

Steele

Torr

Noakes³

et al. 2006

Br J Cancer

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“…Transgelin has been shown to bind to and colocalize with F-actin, indicating that it may be involved in cell differentiation by stabilizing the cytoskeleton through actin binding, 12,13 and diminished expression of this protein has been reported in a variety of cell types on transformation [14][15][16] as well as in several human cancers, including lung, renal, prostate and breast cancer. 14,[17][18][19] According our current knowledge, there are few reports on its role in progression of colorectal cancer.…”

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confidence: 99%

Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients

et al. 2009

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We performed comparative proteomic analysis of colorectal cancer to investigate potential target proteins correlated with carcinogenesis and prognosis. Among them, transgelin, a 22 kDa protein also called SM22, was identified as a novel tumor suppressor protein, but little is known about this protein in tumors so far. A remarkable reduced expression of transgelin was found in colorectal cancer samples compared with normal colorectal mucosa. The effect of 5-aza-2 0 -deoxycytidine as a demethylation agent would obviously restore the original expression level of transgelin, implicating DNA hypermethylation of transgelin is important in the regulation of transgelin transcription in colorectal cancer. As a control, the investigation at cell line level confirms that transgelin protein comes from epithelium but not mesenchymal cells. Further, immunohistochemical staining for transgelin was performed on paraffin sections of 62 and 126 cases of normal colorectal mucosa and colorectal cancer specimens, respectively. As compared to normal colorectal tissue, we observed a significantly lower transgelin expression in colorectal cancer samples (Po0.001). Survival analysis demonstrated that patients without transgelin expression had shorter overall survival, whereas patients with transgelin expression had better survival (P ¼ 0.006). Multivariate analysis showed that negative transgelin expression was an independent prognostic indicator for patient's survival. Our results suggest that transgelin as a suppressor may serve as important biomarker of malignancy. Loss of transgelin involves gene promoter hypermethylation and is closely associated with poor overall survival in colorectal cancer patients.

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“…5D), implying that the overexpression of TAGLN2 could only be partially ascribed to the DNA amplification because there might be multiple mechanisms C18 C05 C35 C04 C09 C06 C24 C51 C16 C19 C08 C39 C21 C28 C10 C27 C41 C11 C23 C30 C02 C03 C12 C07 C14 C20 C34 C22 C13 C32 C26 C38 C36 C37 C17 C31 C29 C33 C40 C01 C12 C28 C03 C07 C08 C09 C05 C02 C10 C22 C14 C23 C30 C17 C16 C13 C15 C21 C11 C01 C09 C18 C22 C40 C19 C41 C38 C26 C23 C24 C29 C21 C36 C08 C17 C25 C04 C11 C05 C37 C32 C06 C30 C31 C33 C02 C34 C14 C28 C07 C03 C12 C16 C27 C10 C20 C39 C13 C15 C35 C01 C13 C15 C28 C07 C08 C03 C05 C12 C10 C02 C09 C23 C14 C17 C16 C21 C22 C30 involved in the upregulation of TAGLN2. In addition, some reports indicated that TAGLN2 was also overexpressed in gastric cancer [34] and HCC [42], where TAGLN2 was even considered as a diagnostic marker for HCC. However, very little is known about the actual effect of TAGLN2 on hepatocarcinogenesis and tumor progress.…”

Section: Tagln2 Involving Chromosome 1q21 In Hccmentioning

confidence: 99%

Correlation between genomic DNA copy number alterations and transcriptional expression in hepatitis B virus‐associated hepatocellular carcinoma

Huang

Sheng²,

Shen

et al. 2006

FEBS Letters

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Human hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, in which the genetic mechanisms of oncogenesis are still unclear. To investigate whether the genomic DNA copy number alterations may contribute to primary HCC, the cDNA microarray-based comparative genomic hybridization (CGH) analysis was here performed in 41 primary HCC infected by hepatitis B virus and 12 HCC cell lines. The resulting data showed that, on average, 7.25% of genomewide DNA copy numbers was significantly altered in those samples (4.61 ± 2.49% gained and 2.64 ± 1.78% lost). Gains involving 1q, 6p, 8q and 9p were frequently observed in these cases; and whilst, losses involving Ip, 16q and 19p occurred in most patients. To address the correlation between the alteration of genomic DNA copy numbers and transcriptional expression, the same cDNA microarray was further applied in 20 HCC specimens and all available cell lines to figure out the gene expression profiles of those samples. Interestingly, the genomic DNA copy number alterations of most genes appeared not to be in generally parallel with the corresponding transcriptional expression. However, the transcriptional deregulation of a few genes, such as osteopontin (SPP1), transgelin 2 (TAGLN2) and PEG10, could be ascribed partially to their genomic aberrations, although the many alternative mechanisms could be involved in the deregulation of these genes. In general, this work would provide new insights into the genetic mechanisms in hepatocarcinogenesis associated with hepatitis B virus through the comprehensive survey on correlation between genomic DNA copy number alterations and transcriptional expression.

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Identification and analysis of tumour-associated antigens in hepatocellular carcinoma

Cited by 84 publications

References 40 publications

The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens

The polycomb group proteins, BMI-1 and EZH2, are tumour-associated antigens

Transgelin as a suppressor is associated with poor prognosis in colorectal carcinoma patients

Correlation between genomic DNA copy number alterations and transcriptional expression in hepatitis B virus‐associated hepatocellular carcinoma

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