Expression of SSX-2 and SSX-4 Genes in Neuroblastoma

The SSX genes are members of the family of cancer/testis antigens that encode tumor-associated antigens recognizable by autologous cytolytic T lymphocytes. Their expression is common in tumors of diverse lineages and absent in normal tissues except testis and thyroid. In this study, sixty-seven neuroblastomas (NB) (12 stage 1, 13 stage 2, 12 stage 3, 12 stage 4S and 13 stage 4) were examined by RT-PCR and a sensitive chemiluminescent detection method for SSX-2 and SSX-4 expression. Seventy-two percent (13/18) of stage 4 NB expressed SSX-2 and 67% (12/18) expressed SSX-4. SSX-2 and SSX-4 positivity correlated with metastatic NB stage 4 (p=0.02 and p=0.006, respectively). Sensitivity experiments showed SSX-2 detection was one tumor cell in 106 normal cells, and one in 104 for SSX-4. All normal tissues (n=6), with the exception of testis, normal bone marrow (BM, n=12) and normal peripheral blood (PBL, n=10) were negative for SSX-2 and SSX-4 expression. Thirty-two BM and 14 PBL obtained from 35 stage 4 NB patients at 24 months from their diagnosis were evaluated for SSX-2 expression. Unlike another cancer/testis antigen, GAGE, only one BM sample was positive, and no prognostic utility could be established. Further investigation of SSX expression at other relevant time points is warranted.

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Validation of immunogenic PASD1 peptides against HLA-A*24:02 colorectal cancer

Immunotherapy ◽

10.2217/imt-2019-0073 ◽

2019 ◽

Vol 11 (14) ◽

pp. 1205-1219 ◽

Cited By ~ 1

Author(s):

Joanne EC Soh ◽

Nadiah Abu ◽

Ismail Sagap ◽

Luqman Mazlan ◽

Azyani Yahaya ◽

...

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Treatment Options ◽

Rt Pcr ◽

Normal Tissues ◽

Cancer Testis Antigens ◽

Protein Expressions ◽

Mrna And Protein Expression ◽

Polymerase Chain ◽

Cancer Testis

Colorectal cancer is the third commonest malignancy in Asia including Malaysia. The immunogenic cancer-testis antigens, which are expressed in a variety of cancers but with limited expression in normal tissues except the testis, represent an attractive approach to improve treatment options for colorectal cancer. We aimed to validate four PASD1 peptides as the immunotherapeutic targets in colorectal cancer. First, PASD1 mRNA and protein expression were determined via real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. The PASD1 peptides specific to HLA-A*24:02 were investigated using IFN-y-ELISpot assay, followed by the cytolytic and granzyme-B-ELISpot assays to analyze the cytolytic effects of CD8+ T cells. Gene and protein expressions of PASD1 were detected in 20% and 17.3% of colorectal cancer samples, respectively. PASD1(4) peptide was shown to be immunogenic in colorectal cancer samples. CD8+ T cells raised against PASD1(4) peptide were able to lyze HLA-A*24:02+ PASD1+ cells. Our results reveal that PASD1(4) peptide represents a potential target for colorectal cancer.

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Prognostic Impact of Cancer Testis Antigens Expression in Advanced Stage Multiple Myeloma Patients.

Blood ◽

10.1182/blood.v110.11.4733.4733 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4733-4733 ◽

Cited By ~ 1

Author(s):

Valéria C.C. Andrade ◽

André L. Vettore ◽

Manuella S.S. Almeida ◽

José S.R. Oliveira ◽

Maria de Lourdes L.F. Chauffaille ◽

...

Keyword(s):

Bone Marrow ◽

Cell Line ◽

Prognostic Impact ◽

Advanced Stage ◽

Normal Tissues ◽

Cancer Testis Antigens ◽

Three Samples ◽

Cox's Regression ◽

Ct Antigens ◽

Cancer Testis

Abstract Background: Cancer testis antigens have become the most extensively studied antigen group in the field of tumor immunology. Aims: This study aims to analyze global expression of 14 CT (cancer/testis) antigens in MM to identify possible prognostic markers and therapeutic targets. Patients and Methods: The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in: 15 normal tissues, one pool of 10 normal bone marrow samples, three normal tonsils and bone marrow aspirates from six normal donors, three monoclonal gammophaties of undetermined significance (MGUS), five solitary plasmacytomas, 39 MM samples (95% advanced stage) and MM cell line U266. CodeLink Human UniSet I Bioarrays 10,000 genes was used for arrays analyses. Results: SPA17 was positive in all normal tissues and was excluded for further analyses. MAGEC1/CT7 was positive in bone marrow aspirates from one MGUS and in one plasmacytoma. U266 cell line was positive for all CT antigens, except SSX1. The frequencies of CT antigens expression in MM patients were: MAGEC1/CT7 = 30/39 (77%); LAGE-1 = 19/39 (49%); MAGEA3/6 = 16/39 (41%); MAGEA2 = 14/39 (36%); GAGE family = 13/39 (33%); NY-ESO-1 = 13/39 (33%); BAGE-1 = 12/39 (28%); MAGEA1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGEA12 = 8/39 (20.5%); MAGEA4 and MAGEA10 = 0%. Cox’s regression model showed that GAGE family positivity and number of positive CT antigens > 6 were independent prognostic factors when all patients were analyzed. However, MAGEC1/CT7 expression was the only independent prognostic factor when non-transplanted patients where analyzed. Three samples predominantly positive (> 6) and three samples predominantly negative (0 or 1) for the 13 analyzed CT antigens were submitted to microarrays analyses. 147 genes were overexpressed in predominantly positive CT antigens samples. Conclusions: Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 seem good candidates for immunotherapy, since together they are overexpressed in 85% of our MM cases. Besides, GAGE family expression, number of CT antigens > 6 and MAGEC1/CT7 seem to have impact on MM prognosis. Also, the results of arrays analyses corroborate the hypothesis that MM can be separate in two groups: predominantly positive and predominantly negative for CT antigens, meaning that these antigens may have important role for MM biology.

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Molecular Profiling of Cancer Testis Antigens in Chronic Lymphocytic Leukemia.

Blood ◽

10.1182/blood.v114.22.4701.4701 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4701-4701

Author(s):

Jason A Dubovsky ◽

Emmanuel Berchmans ◽

John J. Powers ◽

Lin Hui-Yi ◽

Yang Gao ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Fish Analysis ◽

Rt Pcr ◽

Chi Square ◽

Clinical Criteria ◽

Cancer Testis Antigens ◽

Mutational Status ◽

Cancer Testis

Abstract Abstract 4701 Background Chronic Lymphocytic Leukemia (CLL) is characterized by the progressive accretion of long-lived mature B-lymphocytes. Although the classical Rai and Binet staging is still commonly used, a new molecular understanding has identified specific signatures which could help predict disease progression and survival. Given the recent success of immunotherapeutic strategies and immunomodulatory drugs in the treatment of CLL we sought to identify potentially immunologically relevant targets and their relation to well known disease criterion. Methods Our study characterized the mRNA expression of 29 known cancer-testis antigens (CTAs) in 66 patients with CLL at varying stages of disease using a RT-PCR based expression panel. Relevant clinical criterion such as RAI stage, B2m, ZAP-70, IGVH mutational status, CD38, cytogenetics by FISH analysis, WBC count, age, gender, and treatment among others were then taken into account. The binary RNA expression data associated with the clinical and demographic factors were evaluated using chi-square or Wilcoxon rank sum analysis. Results Of the cancer-testis antigens tested, the MAGE family of CTAs revealed statistically significant correlations with multiple clinical criteria. Our analysis reveals a correlation between previous chemo-immunotherapy treatment and MAGE-A1, B2, E1, MAD-CT-2, SPA-17, and PAGE-5 expression. Beyond treatment, total white blood cell count was shown to have a significant association with MAGE family members A1, A3, and B2 expression. In addition, MAD-CT-2 and MAGE-B2 were significantly correlated with the expression of FMC-7 and SSX-4 and LAGE-1 correlated with the presence of B-cell symptomatology. Conclusions Preliminary RT-PCR based CTA phenotyping has unveiled interesting correlations to clinical criteria, opening multiple avenues for future immunotherapeutic interventions as well as possible prognostic value in CLL. Further investigation to better understand the biological value of this information in warranted. Disclosures: Pinilla: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Research Funding; exelixis: Research Funding.

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Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer

Scientific Reports ◽

10.1038/s41598-021-04510-2 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Monireh Mohsenzadegan ◽

Mahdieh Razmi ◽

Somayeh Vafaei ◽

Maryam Abolhasani ◽

Zahra Madjd ◽

...

Keyword(s):

Bladder Cancer ◽

Histological Grade ◽

Immunohistochemical Analysis ◽

Tumor Aggressiveness ◽

P Values ◽

Normal Tissues ◽

Cancer Testis Antigens ◽

Clinicopathological Significance ◽

The Common ◽

Cancer Testis

AbstractMelanoma antigen gene (MAGE)-A6 and MAGE-A11 are two of the most cancer-testis antigens overexpressed in various types of cancers. However, the clinical and prognosis value of MAGE-A6 and MAGE-A11 co-expression in the pathophysiology of the bladder is unknown. Three studies were selected from GEO databases in order to introduce the common genes that are involved in bladder cancer. Then immunohistochemical analysis for staining pattern and clinicopathological significance of suggested markers, MAGE-A6 and MAGE-A11, were performed in 199 and 213 paraffin-embedded bladder cancer with long adjacent normal tissues, respectively. A significant and positive correlation was found between both nuclear and cytoplasmic expressions of MAGE-A6 as well as expression of cytoplasmic MAGE-A11 with histological grade, PT stage, lamina propria invasion, and LP/ muscularis (L/M) involvement (all of the p-values in terms of H-score were < 0.0001). Additionally, significant differences were found between both nuclear and cytoplasmic MAGE-A6/MAGE-A11 phenotypes with tumor size (P = 0.007, P = 0.043, respectively), different histological grades, PT stage, LP involvement, and L/M involvement (all of the p-values for both phenotypes were < 0.0001). The current study added the value of these novel markers to the bladder cancer clinical settlement that might be considered as an admirable target for immunotherapy.

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Gene Expression Profiling and Real-Time PCR Analyses Make It Possible To Identify Novel Potential Cancer-Testis Antigens in Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.1793.1793 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1793-1793

Author(s):

Maud Condomines ◽

Dirk Hose ◽

Thierry Reme ◽

John de Vos ◽

Guilhem Requirand ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Real Time ◽

Expression Profiles ◽

Differentially Expressed ◽

Rt Pcr ◽

Normal Tissues ◽

Present Call ◽

The Mean ◽

Cancer Testis

Abstract The identification of novel tumor-associated antigens is critical for the development of immunotherapeutic strategies. Cancer-testis (CT) antigens represent attractive targets due to their restricted pattern of expression. More than 90 CT genes have been previously classified into four categories according to their expression profiles: testis-restricted (expression in testis and tumor samples only), “tissue restricted” (mRNA detected in 2 or fewer non-gametogenic tissues), “differentially expressed” (mRNA detected in three to six non-gametogenic tissues), and “ubiquitously expressed”. Among those, we previously reported that 18 CT genes were expressed by primary myeloma cells (MMC) of more than 10% of patients with multiple myeloma (MM). This study aimed at finding novel putative CT genes expressed in MM using cDNA microarray analysis and real-time RT-PCR validation. Gene expression profiles of 5 testis samples, 64 MMC, 7 normal memory B cell (MB), 7 normal bone marrow plasma cell samples and 23 normal tissue samples available on a public database were obtained using Affymetrix U133AB microarrays. Out of 45000 probe sets of Affymetrix U133 AB chips, we selected 16982 probe sets which had a “Present” Affymetrix Call in MMC of at least 6/64 patients and in 3/5 testis samples. In order to select genes with a similar pattern of expression than the known CT genes, we developed 4 independent filters making it possible to keep a high number of known CT genes while decreasing the total number of probe sets. Firstly, 2514 of 16982 probe sets had a ratio of the mean signal in MMC with a Present call / mean signal in MB > 2.5. Secondly, 541 of these 2514 probe sets had a Present call in less than 7 of the 23 normal tissues. Thirdly, 333 of these 541 probe sets had a ratio of the mean signal in MMC with a Present call / mean signal in MMC with an Absent call > 2.5. Fourthly, we removed genes whose expression profiles were discordant with different probe sets or discordant with data of the literature. The final probe set list contains 88 probe sets which include 13 of 18 known CT genes reported in MM, thus resulting in a 190-fold enrichment. The expression in 13 normal tissues and in MM samples of 21 out of these 75 putative novel CT genes was investigated by real time RT-PCR. Seven genes were ubiquitously expressed or poorly expressed in MMC samples and further deleted. According to the previously defined CT gene categories, we found one novel “testis-restricted” (TEX14), 8 “tissue-restricted” and 5 “differentially expressed” CT genes. Immunogenicity of one gene product - IGSF11 - was already demonstrated in other cancers by identifying a T-cell epitope. Two genes - NLGN4X and FAM133A - are located in X chromosome and 2 genes - CTNNA2 and FAM133A - are expressed only in brain and testis. In conclusion, by analyzing gene expression patterns with Affymetrix microarrays, we found 75 novel putative CT antigen candidates expressed in MMC of 10 to 100% of patients. Real time RT-PCR validation made it possible to confirm the CT status of 14 genes out of the 21 tested. Further studies are warranted to determine their immunogenicity.

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Treatment of Chronic Lymphocytic Leukemia with a Hypomethylating Agent Induces Expression of NXF2, An Immunogenic Cancer Testis Antigen

Blood ◽

10.1182/blood.v112.11.4207.4207 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4207-4207

Author(s):

Jason A Dubovsky ◽

Douglas G McNeel ◽

John J. Powers ◽

Eduardo M. Sotomayor ◽

Javier Pinilla

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Antigen Presentation ◽

Lymphocytic Leukemia ◽

Active Immunotherapy ◽

Aberrant Expression ◽

Normal Tissues ◽

Cancer Testis Antigens ◽

Solid Malignancies ◽

Specific Proteins ◽

Cancer Testis

Abstract Critical to success of active immunotherapy against cancer is the identification of immunologically recognized cancer-specific proteins with low tolerogenic potential. Cancer testis antigens (CTAs) in particular, fulfill this requirement as a result of their aberrant expression restricted to cancer cells and lack of expression in normal tissues bypassing tolerogenic mechanisms against self. Although CTAs have been extensively studied in solid malignancies little is known regarding their expression in chronic lymphocytic leukemia (CLL). Using a two-pronged approach we evaluated the immunogenicity of 29 CTAs in 22 patients with CLL and correlated these results to RTPCR data from CLL cell lines and patient cells. We identified IgG specific antibodies for one antigen, NXF2 and confirmed this response by ELISA and Western blot. We found that treatment of CLL with 5-aza-2′-deoxycytidine can induce expression of NXF2 that lasted for several weeks after treatment. Treatment also increased levels of MHC and costimulatory molecules (CD80, CD86, and CD40) necessary for antigen presentation. In addition, we identified other promising antigens such as NY-ESO-1 and MAGE which may have potential immunotherapeutic application. Our findings suggest that NXF2 could be further pursued as an immunotherapeutic target in CLL, and that treatment with demethylating agents could be exploited to specifically modulate CTA expression and effective antigen presentation in malignant B-cells.

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Cancer-testis gene-expression features in various tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14260 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14260-e14260

Author(s):

Kristina I. Soldatova ◽

Oleg Ivanovich Kit ◽

Roman E. Tolmakh ◽

Liubov Yu Vladimirova ◽

Denis S. Kutilin

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Transcriptional Activity ◽

Test Results ◽

Cdna Synthesis ◽

Normal Tissues ◽

Cancer Testis Antigens ◽

Tumor Tissues ◽

Real Time Qpcr ◽

Cancer Testis

e14260 Background: Cancer-testis antigens (CTA) can be an effective target for immunotherapy. Immunotherapeutic approaches targeting CTA in breast cancer (BC), endometrial cancer (EC), ovarian cancer (OC), and colon cancer (CRC) are in the incipient stages of development. The purpose of our study was screening of CTA specific for BC, EC, OC and CRC, based on an analysis of transcriptional profiles of CT-genes. Methods: Tumor and intact tissues of the breast, uterus, ovaries and colon were studied in 35, 30, 20 and 60 patients, respectively. RNAs were isolated using the method described by Chomczynski and Sacchi (2006). The REVERTA-L reagent kit was used for the cDNA synthesis. Relative expression of 16 genes ( MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NYESO1, SSX2, SCP1, PRAME1) was determined by Real-Time qPCR (with GAPDH and GUSB as reference genes). Statistical analysis was performed using the Mann-Whitney test. Results: BC patients showed significantly (p < 0.005) increased expression of MAGEA3, MAGEA4 and GAGE3 in tumor tissues compared to normal ones; EC patients - significantly (p < 0.05) increased expression of MAGEA1, MAGEA2, MAGEA4, MAGEB2, GAGE3, NY-ESO1, SCP1 and PRAME1 in tumor tissues compared to normal ones; OC patients - significantly (p < 0.05) increased expression of MAGEB1, MAGEB2, GAGE1, NY-ESO1 and decreased expression of MAGEA3, MAGEA4, GAGE3, GAGE4, XAGE3, SSX2, SCP1 and PRAME1; CRC patients - significantly (p < 0.05) increased expression of SSX2 and PRAME1, together with decreased BAGE expression, in tumors compared to normal tissues. Conclusions: Analysis of the transcriptional activity of CT-genes revealed the most common diagnostic markers and immunotherapeutic targets for every malignancy: in BC - MAGEA3, MAGEA4 and GAGE3, in EC - MAGEA1, MAGEA2, MAGEA4, MAGEB2, GAGE3, NY-ESO1, SYCP1 and PRAME1, in OC - MAGEB1, MAGEB2, GAGE1 and NY-ESO, in CRC - SSX2 and PRAME1.

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Evaluating sugarcane families by the method of Dynamic Technique for Order Preference by Similarity to Ideal Solution (DTOPSIS)

Bragantia ◽

10.1590/1678-4499.0126 ◽

2014 ◽

Vol 73 (3) ◽

pp. 229-236

Author(s):

Peifang Zhao ◽

James Todd ◽

Jun Zhao ◽

Jiayong Liu ◽

Li Yao ◽

...

Keyword(s):

Ideal Solution ◽

Selection Efficiency ◽

Family Selection ◽

Dynamic Technique ◽

Ideal Family ◽

Stage 4 ◽

The Family ◽

Order Preference ◽

Stage 1 ◽

The Ideal

Enlarging the quantity of seedlings of elite families and discarding inferior sugarcane (Saccharum spp.) families could improve sugarcane breeding and selection efficiency. The feasibility of using the method Dynamic Technique for Order Preference by Similarity to Ideal Solution (DTOPSIS) method was explored to identify superior sugarcane families. Data on 5 traits: Brix, millable stalks per stool (MS), stalk diameter (SD), plant height (PH), and percent pith were collected from two family trials having 17 families and two check cultivars at two sites including plant-cane and first-ratoon crops. The rest of the seedlings were planted into field for routine selection in the regular program. The DTOPSIS method calculates a comprehensive index (Ci) which expresses the closeness of a solution to the ideal solution and was used in this study to test the distance of each family to the ideal family. The Ci of the families was compared to the family selection rate in the regular program by determining the selection rate at Stage 1 to Stage 4 for each family in the regular program. The result indicated that the Ci values calculated from family trials were significantly (p<0.01) correlated to the selection rate at Stage 2 (r=0.8059), Stage3 (r=0.7967), and Stage 4 (r=0.8202), and indicating that promising clones were selected from families with higher Ci values in the family trial. Thus, it could be feasible to use DTOPSIS to determine elite sugarcane families and to eliminate inferior families and thereby, increasing the variety selection efficiency.

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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Expression of Cancer Testis Antigens in Tumor-Adjacent Normal Liver Is Associated with Post-Resection Recurrence of Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13102499 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2499

Author(s):

Lisanne Noordam ◽

Zhouhong Ge ◽

Hadiye Özturk ◽

Michail Doukas ◽

Shanta Mancham ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Normal Liver ◽

Occult Metastasis ◽

Recurrence Rates ◽

Curative Intent ◽

Cancer Testis Antigens ◽

Negative Prognostic Factor ◽

Increased Risk ◽

Hcc Recurrence ◽

Cancer Testis

High recurrence rates after resection of hepatocellular carcinoma (HCC) with curative intent impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims were to identify CTAs that are frequently and selectively expressed in HCC-tumors, and to investigate whether CTAs could serve as biomarkers for occult metastasis. Tumor and paired tumor-free liver (TFL) tissues of HCC-patients and healthy tissues were assessed for mRNA expression of 49 CTAs by RT-qPCR and protein expression of five CTAs by immunohistochemistry. Twelve CTA-mRNAs were expressed in ≥10% of HCC-tumors and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA-expression in TFL was an independent negative prognostic factor for post-resection HCC-recurrence and survival. We established a panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients. The increased risk of HCC-recurrence in patients with CTA expression in TFL, suggests that CTA-expressing (pre-)malignant cells may be a source of HCC-recurrence, reflecting the relevance of targeting these to prevent HCC-recurrence.

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