Expression of cancer/testis (CT) antigens in Chinese hepatocellular carcinoma and its correlation with clinical parameters

Peng, Jie; Chen, Hongsong; Mou, Dong-Cheng; Cao, Ji; Xu, Cong; Qin, Liu-liang; Wei, Lai; Leng, Xi-sheng; Wang, Yu; Chen, Weifeng

doi:10.1016/j.canlet.2004.07.028

Cited by 67 publications

(67 citation statements)

References 21 publications

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“…41 In ovarian cancer, higher frequencies of NY-ESO-1 expression were found in serous carcinomas, whereas tumours of borderline malignancy or cystadenomas were negative. 47 In another study, no relationship was found between NY-ESO-1 expression and ovarian cancer grade although 96% of patients in this series had advanced stage disease, so no real assessment was undertaken of patients whose disease carried a good prognosis. 28,46 In SCC of the head and neck, NY-ESO-1 expression was less frequent than for MAGE-A1 and MAGE-A3.…”

Section: Factors Affecting Ny-eso-1 Expression In Tumoursmentioning

confidence: 70%

“…In contrast, NY-ESO-1 expression has also been reported in earlier stages of disease, premalignant lesions or cancers that retain a differentiated phenotype. Examples include SCC of the oesophagus, 27 one series of hepatocellular carcinoma, 47 carcinoma-in situ of the testis 22 and fibro-adenomas of the breast. 5 …”

Section: Factors Affecting Ny-eso-1 Expression In Tumoursmentioning

confidence: 99%

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Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

et al. 2006

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Summary Since the early 1990s, numerous cancer Ag have been defined and for a handful of these there is now some clinical experience, which has made it possible to assess their value as targets for cancer immunotherapy. The cancer-testis Ag have been particularly attractive because their expression is limited to cancer and virtually no nonmalignant cells apart from germ cells and trophoblast. Among these, NY-ESO-1 has been the focus of our attention. The exceptional immunogenicity of this Ag coupled with its widespread distribution among many cancer types make it a very good vaccine candidate, with the potential to be used in vaccines against many types of malignancies. This article reviews emerging knowledge about the biology of NY-ESO-1 and experience with the early clinical development of vaccines directed against NY-ESO-1. These early studies have yielded a wealth of information about the immunology of NY-ESO-1 and set the scene for future clinical strategies for immune targeting of cancer.Key words: cancer immunology, cancer-testis Ag, cancer vaccine, dendritic cell, ISCOMATRIX, NY-ESO-1. Biology of NY-ESO-1NY-ESO-1 was first discovered using 'SERological identification of antigens by recombinant EXpression cloning' (SEREX). This is a method used for identifying the antibody repertoire of cancer-bearing patients by screening their serum against an expression library that typically displays protein Ag derived from a cancer source such as an autologous tumour or a cell line. In this case, NY-ESO-1 was found by using serum from a patient with squamous cell carcinoma (SCC) of the oesophagus. 1,2 Expression of NY-ESO-1 protein has been shown in multiple cancer types (Table 1), as well as in spermatogonia, oogonia and placenta. 3,4 Although NY-ESO-1 mRNA expression has been detected at low levels in some other normal tissues, it is unclear whether this is significant in the absence of detectable protein. 4,5 Other genes with similar names (NY-ESO-2, -3, -4, -5, -6, -7, -8) have no homology with NY-ESO-1. 2 The NY-ESO-1 gene is located on chromosome Xq28, 1 which carries a disproportionately high number of cancertestis (CT) Ag genes. 6 Up to 10% of the genes on chromosome X are CT Ag genes. The expression of these genes seems to be related to the demethylation of the promoter regions because experimental demethylation leads to the upregulation of CT Ag expression. [7][8][9][10][11][12][13][14][15][16][17][18] The NY-ESO-1 gene encodes a protein of 180 amino acids with M r 18 kDa, 2 which is expressed primarily in the cytoplasm although nuclear expression can be seen in some spermatogonia. 4 A homologue of NY-ESO-1, termed LAGE-1, was identified using representational difference analysis. 14 LAGE-1 and NY-ESO-1 are 84-89% homologous at the protein level. 14 Alternative splicing of LAGE-1 mRNA leads to the expression of two major transcripts encoding proteins of 210 and 180 amino acids, respectively. LAGE-1 is expressed in a wide variety of cancers (Table 1), usually, but not always, in conjunction with NY-ESO-1 or ...

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Section: Factors Affecting Ny-eso-1 Expression In Tumoursmentioning

confidence: 70%

Section: Factors Affecting Ny-eso-1 Expression In Tumoursmentioning

confidence: 99%

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

et al. 2006

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“…The malignant transformation of these antigens is frequently associated with the activation or depression of genes, resulting in the expression of the antigens. More than 50 types of CTA have been identified thus far, including MAGE, GAGE, PAGE, NY-ESO-1, SSX, SPANX and XAGE (4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Hepatocellular carcinoma patients highly and specifically expressing XAGE-1 exhibit prolonged survival

et al. 2010

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Abstract. XAGE-1 is classified into the group of a new family of cancer-testis antigens (CTA) and has the four transcript variants of XAGE-1a, XAGE-1b, XAGE-1c and XAGE-1d. Immunohistochemistry was used to investigate the expression of XAGE-1 transcript variants in Chinese patients with hepatocellular carcinoma (HCC). Reverse transcriptionpolymerase chain reaction (RT-PCR) and real-time RT-PCR were used to analyze XAGE-1 gene expression, and XAGE-1 protein expression was examined by immunohistochemistry. Furthermore, the clinical correlation of XAGE-1 expression was analyzed. The expression of the XAGE-1 mRNA was investigated in the tissues of 96 HCC patients and all XAGE-1 isoforms were detected in these tissues. Three types of XAGE-1 transcript variants (XAGE-1b, XAGE-1c and XAGE-1d) showed high specific and frequent expression in HCC tissues, with the positive expression rate of XAGE-1b, XAGE-1c and XAGE-1d being 41.7% (40/96), 15.6% (15/96) and 26.0% (25/96), respectively. XAGE-1b was the dominant type, but none of the three were detected in adjacent non-HCC tissues. Only 2 cases of XAGE-1a mRNA expression were observed. Moreover, XAGE-1 protein was detected in 39 of 96 HCC patients, but none in the adjacent non-cancerous tissue and normal liver tissue. No relationship was found between the expression of XAGE-1 and clinical parameters, such as age, gender, tumor size, TNM staging, serum AFP level and infection with hepatitis virus. Patients with XAGE-1b-positive transcript variant exhibited shorter 2-year survival times. The high frequency and specificity of XAGE-1, particularly XAGE-1b, in HCC indicates that their products may predict the prognosis of HCC patients and be novel targets for antigen-specific immunotherapy to HCC.

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“…SPAG9 belongs to the c-Jun-NH 2 terminal kinase-interacting protein family (28). Proteins from this family function in cell growth, proliferation, apoptosis and tumor development (29,30), and are expressed in renal cell carcinoma, and ovarian, cervical, breast, thyroid and colorectal cancer tissues, SPAG9 provokes a strong humoral immune response, and its autoantibody can be detected in the peripheral blood of patients with the aforementioned types of cancer (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). The current study hypothesized that anti-SPAG9 antibody may be detected in the peripheral blood of patients with HCC, and that, in combination with serum AFP levels, it may provide a reliable diagnostic test for HCC, particularly for AFP-negative patients.…”

Section: Introductionmentioning

confidence: 99%

“…The expression of these antigens is normally restricted to the testis, but these antigens are also expressed (22)(23)(24). Several studies have revealed that CTAs are highly expressed in the tumor tissue of patients with HCC (25)(26)(27). SPAG9 belongs to the c-Jun-NH 2 terminal kinase-interacting protein family (28).…”

Section: Introductionmentioning

confidence: 99%

Serum levels of anti‑sperm‑associated antigen 9 antibody are elevated in patients with hepatocellular carcinoma

Ren

Zou

et al. 2017

Oncol Lett

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Abstract. At present, there is a high incidence of viral hepatitis and high mortality rates due to hepatocellular carcinoma (HCC) in China. In the current study, the quantification of antibodies against the cancer-testis antigen sperm-associated antigen 9 (SPAG9), alone and combined with α-fetoprotein (AFP), were evaluated as biomarkers for the diagnosis of HCC. The levels of anti-SPAG9 antibody and AFP were quantified in serum samples from patients with HCC and hepatitis or cirrhosis, as well as healthy volunteers. The results revealed that the serum levels of anti-SPAG9 immunoglobulin G antibody in patients with HCC were significantly higher compared with those in patients with hepatitis/cirrhosis and healthy controls. Using receiver operator characteristic curves, the area under the curve (AUC, 0.870) of SPAG9 as a diagnostic marker of HCC was significant [P<0.001; 95% confidence interval (CI), 0.793-0.947], whereas the AUC of AFP was 0.832 (P<0.001; 95% CI, 0.736-0.928). Serum anti-SPAG9 antibody levels exhibited significant potential for the differential diagnosis of HCC, with an AUC value of 0.729, (P=0.008; 95% CI, 0.559-0.899). Similarly, serum AFP levels exhibited significant value for the differential diagnosis of HCC, with an AUC value of 0.842 (P<0.001; 95% CI, 0.732-0.953). When combined with quantification of AFP, the diagnostic sensitivity and specificity of anti-SPAG9 levels were increased. In summary, the results suggested that anti-SPAG9 antibody is a potential early diagnostic marker of HCC. IntroductionHepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major risk factors for the development of human hepatocellular carcinoma (HCC) (1-3). The incidence of HCC in China is ~100/100,000 population, and a principal component of the attributable risk is chronic HBV infection (4), with >50% of the global HCC burden attributed to HBV (5). In China, ~10% of patients with HCC suffer from HCV infection, and certain patients have HBV and HCV co-infections (6). In the USA, Europe and Japan, >50% of current cases of HCC are attributable to HCV infection, and the majority of these patients have cirrhosis (7-9). The time from initial diagnosis of chronic hepatitis to the development of HCC may span several decades; once cirrhosis is established, HCC develops at a yearly rate of 1-4% (10).In China, the majority of patients with HCC present with advanced-stage disease, and HCC has become the second leading cause of mortality (11). Early diagnosis relies on non-invasive biomarkers, imaging and clinical parameters, with markers such as α-fetoprotein (AFP), the proportion of the fucosylated isoform of AFP to total AFP, AFP-L3 and des-gamma-carboxy-prothrombin (DCP) being Food and Drug Administration-approved for use in the surveillance of high-risk populations (12,13). However, the clinical value of these biomarkers is a subject of debate (14). In Japan, three biomarkers are combined for surveillance (15,16), and this combined testing has a high level of sensitivity and specificity (17,18). In Ch...

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Expression of cancer/testis (CT) antigens in Chinese hepatocellular carcinoma and its correlation with clinical parameters

Cited by 67 publications

References 21 publications

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

Hepatocellular carcinoma patients highly and specifically expressing XAGE-1 exhibit prolonged survival

Serum levels of anti‑sperm‑associated antigen 9 antibody are elevated in patients with hepatocellular carcinoma

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