The potential value of cancer-testis antigens in ovarian cancer: Prognostic markers and targets for immunotherapy.

BACKGROUND: Tumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response. AIMS: This review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy. METHODS: We analyzed publications and outlined a comprehensive of overview the regulatory mechanism, immunogenicity, clinical expression significance, tumorigenesis, and application prospects of CTA in ovarian cancer, with a particular focus on recent progress in CTA-based immunotherapy. RESULTS: The expression of CTA affects the occurrence, development, and prognosis of ovarian cancer and is closely related to tumor immunity. CONCLUSION: CTA can be used as a biomarker for the diagnosis and prognosis evaluation of ovarian cancer and is an ideal target for antitumor immunotherapy. These findings provide novel insights on CTA in the improvement of diagnosis and treatment for ovarian cancer. The successes, current challenges and future prospects were also discussed to portray its significant potential.

The trend of lymphoma incidence in China from 2005 to 2017 and lymphoma incidence trend prediction from 2018 to 2035: a log-linear regression and Bayesian age-period-cohort analysis.

Objectives: The aims of this study were to explore the incidence characteristics and trend prediction of lymphoma from 2005 to 2035, and to provide data basis for the prevention and control of lymphoma in China. Method: The data on lymphoma incidence in China from 2005 to 2017 were obtained from the Chinese Cancer Registry Annual Report. The Joinpoint regression model was used to calculate annual percentage change (APC) and average annual percentage change (AAPC) to reflect time trends. Age-period-cohort models were conducted to estimate age, period, and cohort effects on the lymphoma incidence. A Bayesian age-period-cohort model was used to predict lymphoma incidence trends from 2018 to 2035. Results: From 2005 to 2017, the incidence of lymphoma was 6.26/100,000, and the age-standardized incidence rate (ASIR) was 4.11/100,000, with an AAPC of 1.4% [95% confidence interval (CI): 0.3%, 2.5%]. The ASIR was higher in men and urban areas than in women and rural areas, respectively. The age effect showed that the incidence risk of lymphoma increased with age. In the period effect, the incidence risk of lymphoma in rural areas decreased first and then increased with 2010 as the cutoff point. The overall risk of lymphoma incidence was higher in the cohort before the 1970-1974 birth cohort than in the cohort after. From 2018 to 2035, the lymphoma incidence in men, women, and urban areas will show an upward trend. Conclusion: From 2005 to 2017, the incidence of lymphoma showed an increasing trend, and was different in regions, genders, and age groups in China. It will show an upward trend from 2018 to 2035. These results are helpful for the formulation and adjustment of lymphoma prevention, control, and management strategies, and have important reference significance for the treatment of lymphoma in China.

The evolution of preexisting primary immune thrombocytopenia after COVID-19 onset: A nationally representative, prospective, multicentre, observational study.

The symptoms in patients with primary immune thrombocytopenia (ITP) after COVID-19 onset remain largely unclear. The aim of this study was to describe the platelet count fluctuations in ITP patients following the diagnosis of COVID-19. A prospective multicentre observational study was conducted from December 15th, 2022, to January 31st, 2023 in 39 general hospitals across China. Patients with preexisting primary ITP who were newly diagnosed with COVID-19 were enrolled. A total of 1216 ITP patients with newly-diagnosed COVID-19 were enrolled. 375 (30.8%) patients experienced ITP exacerbation within eight weeks after the diagnosis of COVID-19, and most exacerbation (266/375, 70.9%) developed in the first two weeks. Immunosuppressive therapy for ITP and severe/critical COVID-19 infection were independent variables associated with ITP exacerbation. Overall the platelet count had a transient increasing trend, and the platelet peak value occurred at two weeks after COVID-19 infection. Then, the platelet count decreased to the baseline level in the following weeks. The platelet count had a transient increasing trend in ITP patients following the diagnosis of COVID-19. ITP exacerbation only occurred in less than one-third of ITP patients. Nonimmunosuppressive therapy may have an advantage to prevent ITP exacerbation during COVID-19.

Prediction and identification of HLA-A*0201-restricted epitopes from cancer testis antigen CT23.

Cancer-testis antigen CT23 is a class of tumor-associated antigens (TAA) characterized by restricted expression in male germ cells and a variety of tumor tissues. Numerous studies have shown that CT23 is closely related to tumor cell viability, proliferation, metastasis and invasion. CT23 is immunogenic and can cause specific immune response in tumor patients. Therefore, it is considered to be one of the best target antigens for designing therapeutic tumor vaccines and T-cell-mediated tumor immunotherapy. In this study, we initially obtained seven HLA-A*0201-restricted CT23 epitope candidate peptides through the T cell epitope prediction program. Subsequently, a T2 cell binding assay revealed the potential binding of all candidate peptides with HLA-A2 molecules. Notably, peptide P7 (ALLVLCYSI) exhibited the highest affinity, as evidenced by a fluorescence index (FI) of 2.19. Dendritic cells (DCs) loaded with CT23 candidate peptide can stimulate CD8+T cell activation and proliferation, and compared with other candidate peptides, candidate peptide P7 is superior. The cytotoxic T lymphocytes (CTLs) stimulated by the peptide P7 had killing effect on tumor cells (HLA-A*0201+, CT23+), but no killing effect on tumor cells (HLA-A*0201-, CT23+). The CTLs induced by the peptide P7 also had a specific killing effect on T2 cells bearing the peptide P7. In summary, our findings suggest that the CT23 peptide P7 (ALLVLCYSI) can induce immune responses and holds potential for tumor-specific CTL therapy.

A life-threatening bleeding prediction model for immune thrombocytopenia based on personalized machine learning: a nationwide prospective cohort study.

Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.

Identification of potential biomarkers in cancer testis antigens for glioblastoma.

OBJECTIVE: To screen and validate cancer testis antigens (CTAs) as potential biomarkers and explore their molecular mechanisms in glioblastoma (GBM). METHODS: Ribonucleic acid sequencing (RNA-seq) and bioinformatics analyses were utilized to screen the highly expressed CTAs in GBM. Correlation analysis was used to identify potential biomarkers associated with tumor purity and prognosis. Immunohistochemistry was applied for detection of protein expression. Protein-protein interaction (PPI) network construction, functional enrichment analysis, and binding domain prediction were performed to investigate the underlying molecular mechanisms of GBM. RESULTS: A total of 8 highly expressed CTAs were identified in GBM. One of them was PDZ-binding kinase (PBK). PBK messenger RNA (mRNA) was most highly expressed in GBM and associated with tumor purity and prognosis, PBK protein expression was also significantly increased in GBM tissues and correlated with p53 expression. Functional enrichment analysis revealed that the PBK related genes were predominantly enriched in cell cycle pathway with 38 genes enriched. The proteins encoding by these 38 genes were performed by binding domain prediction analysis, which demonstrated 15 proteins interacting with PBK. Most of these proteins were up regulated in GBM. CONCLUSION: PBK is highly expressed in GBM. It may serve as a potential biomarker for GBM targeting therapy and the cell cycle modulator by interacting with certain key molecules of cell cycle in GBM.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM), the most malignant intracranial neoplasm, is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor. Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis, diagnosis, and treatment. Due to the limitations of therapeutic effects, this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets. METHODS: The expression profile of mRNAs in GBM was detected by RNA-sequencing, and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database. Of the total 40 hub genes, FN1, P4HB, and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases. The validation of FN1, P4HB, and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution. RESULTS: Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival (OS) of GBM patients (P<0.05). Multivariate analysis showed that FN1 overexpression (HR=9.199, P=0.002) was an independent and unfavorable prognostic factor for GBM patients. The median survival time was 8.5 months and 21 months for high and low expressions of FN1, respectively. CONCLUSION: It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma.

Objective: The study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma. Methods: The expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo. Results: MAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma. Conclusion: MAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.

FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy.

OBJECTIVE: Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer, but not in normal tissues except for testis. This study aimed to investigate the expression and functional role of FMR1NB in glioma. METHODS: The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry, respectively, in glioma specimens from 83 patients at follow-up. The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines A172 and U251. RESULTS: FMR1NB mRNA and protein expression was detected in 58.8% (77/131) and 46.34% (57/123) of glioma tissues, respectively. FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome. Knockdown of FMR1NB induced apoptosis and suppressed proliferation, adhesion, migration, and invasion by modulating the expression of cyclin A, CDK2, caspase-3, E-cadherin, and N-cadherin in A172 and U251 cells. CONCLUSION: Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

Microrna-1224-5p Is a Potential Prognostic and Therapeutic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Analyses.

OBJECTIVE: Glioblastoma (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and high recurrence rate. It's known that some microRNAs (miRNAs) which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM. This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker. METHODS: Differentially expressed miRNAs (DEmiRNAs) were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus (GEO) database through bioinformatics tools. The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas (CGGA). Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database. TAM2.0 database, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the function of the dysregulated miRNAs. Subsequently, protein-protein interaction (PPI) network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs, respectively. Then, core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks. Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues. Furthermore, the potential biomarkers were identified by clinical correlation analysis and survival analysis. RESULTS: Totally, 68 intersecting DEmiRNAs were identified, 40 of which were upregulated and the other 28 miRNAs were downregulated. Two upregulated and 4 downregulated miRNAs showed prognostic significance. Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p, which were respectively upregulated and downregulated in GBM. The correlation between miR-1224-5p level and recurrence was statistically significant (P=0.011). Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis. Moreover, high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis. CONCLUSION: MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.

Immunohistochemistry Study of OY-TES-1 Location in Fetal and Adult Human Tissues.

OY-TES-1 is reportedly involved in carcinogenesis and spermatogenesis. However, the tissue distribution of OY-TES-1 in the normal human body remains elusive. This study detected OY-TES-1 expression in human fetal and adult normal tissues by immunohistochemistry. We identified a general principle of OY-TES-1 expression. The expression of OY-TES-1 was found in neurons, smooth muscle cells, and cardiac muscle cells from both fetuses and adults. The connective tissue showed no specific staining throughout the fetal and adult samples. With OY-TES-1-positive staining of the epithelium irregular, OY-TES-1 was strongly expressed in the epithelium of the skin and bladder, as well as hepatocytes, pancreatic islets, and acinous cells during the fetal stage but was not detected in the postnatal period. In contrast to the epithelium of blood vessels, the fetal and adult central hepatic vein and glomeruli showed negative expression of the OY-TES-1 protein. Sex-dimorphism was observed in the distribution of OY-TES-1 in male and female germ cells. Collectively, our results indicate that OY-TES-1 is a member of the cancer-testis antigen and autoantigen, with tissue-specific and period-specific expression patterns, revealing potential contributions of OY-TES-1 to the diagnosis and therapeutic treatment for neoplasms and infertility.

Cancer-testis antigen ACRBP expression and serum immunoreactivity in ovarian cancer: Its association with prognosis.

INTRODUCTION: Cancer testis (CT) antigens are attractive targets for cancer immunotherapy because of their expression restriction and immunogenicity. The acrosin binding protein (ACRBP) is a member of CT antigens. This study aimed to evaluate ACRBP expression and immunogenicity in ovarian cancer (OC). METHODS: The expression level of ACRBP in OC tissues, normal ovarian tissues, and cell lines was detected via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. We determined the levels of ACRBP antigen and antibody in serum samples collected from patients with OC and healthy donors using enzyme-linked immunosorbent assays (ELISA), the level of ACRBP in cell-cultured medium was also tested. RESULTS: ACRBP mRNA and protein expressions were upregulated in OC tissues relative to normal tissue, especially highly expressed in epithelial ovarian cancer (EOC). Moreover, ACRBP expression was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and chemosensitivity. Serological analysis showed that anti-ACRBP antibody was detected in the sera of 16 of the 56 (28.5%) patients with OC but not in healthy donors. The area under the receiver operating characteristic curve for ACRBP antibody was 0.802 (95% confidence interval [CI]: 0.708-0.876), and the sensitivity and specificity for ACRBP antibody was 85.71% and 55.0%, respectively. Kaplan-Meier analysis revealed that the overall survival (OS) and disease-free survival (DFS) in OC patients with high ACRBP expression were significantly lower than those with low expression (p = 0.040, p = 0.021). However, ACRBP antibody level was not associated with prognosis. CONCLUSION: ACRBP expression was upregulated in OC tissues and induced humoral immune response in patients with OC, suggesting that ACRBP is a potential prognostic biomarker and a target of tumor immunotherapy for OC.

Combined treatment with epigenetic agents enhances anti-tumor activity of T cells by upregulating the ACRBP expression in hepatocellular carcinoma.

OBJECTIVE: To evaluate the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA) and trichostatin A (TSA) on immunotherapy with a murine model of hepatocellular carcinoma (HCC). METHODS: Dendritic cells (DCs) transduced with recombinant lentivirus expressing a cancer-testis antigen, acrosin binding protein (ACRBP), are referred to as DC/ACRBP. CD8+ T cells were harvested from spleens of C57BL/6 mice and activated by DC/ACRBP. Cytotoxicity of DC/ACRBP-activated T cells was analyzed by cytotoxicity and murine xenograft assays. RESULTS: Cytotoxicity assay results revealed that DC/ACRBP-activated T cells exhibited the highest cytotoxicity against HCC cells pre-treated with triple drugs (DAC+VPA+TSA) compared with dual drugs (DAC+VPA and DAC+TSA) and single drug (DAC, VPA and TSA) respectively. Analyses of RT-PCR and immunoblotting demonstrated that the highest ACRBP expression of HCC cells was induced by the triple drugs compared with the single and dual drugs. These results indicated that DC/ACRBP-activated T cells might be ACRBP-specific lymphocytes, and the augmented cytotoxicity may be dependent on the upregulation of ACRBP expression. These assumptions were further confirmed by xenograft tumor assay. Tumor cells of mice administrated with the triple drugs exhibited increased ACRBP expression compared with those of mice without administration. As expected, DC/ACRBP-activated T cells adopted by mice injected with the triple drugs, compared with those adopted by mice without injection, remarkably impeded growth and facilitated apoptosis of tumor cells. CONCLUSION: These data suggested that combined treatment with DAC, VPA and TSA may enhance the anti-tumor efficacy of ACRBP-specific T cells by upregulating ACRBP expression in HCC.

Synergistic regulation of methylation and SP1 on MAGE-D4 transcription in glioma.

BACKGROUND: The family of MAGE genes is well known due to the majority of MAGE genes expressing specifically in tumor tissues while restrictedly in normal tissues. MAGE-D4 is one of the MAGE family and considered as a promising target for glioma immunotherapy because of its overexpression in glioma and restricted expression in normal tissues. Whereas the mechanism of MAGE-D4 heterogeneous expression in glioma has not yet been elucidated. In this study, the transcriptional regulation mechanism of MAGE-D4 in glioma is focused from the perspectives of promoter methylation and SP1. METHODS: Dual-luciferase reporter assay was performed to identify the core promoter of MAGE-D4 gene. Mass spectrometry was applied to quantify the methylation status of MAGE-D4 promoter in 50 glioma and 9 normal brain tissues. The influence of methylation and SP1 on MAGE-D4 transcriptional activity was evaluated by dual-luciferase reporter assay, qRT-PCR, western blot and ChIP-qPCR. Decitabine, an epigenetic drug, was used to treat the glioma cells. Then the treated cells were evaluated the influence of demethylation on SP1 binding to MAGE-D4 promoter. RESULTS: The -358 to +172 bp region was identified as the core promoter of MAGE-D4 gene which demonstrated hypomethylated and negative correlation between methylation level and MAGE-D4 mRNA expression in glioma tissues. For single CpG unit analysis, 8 CpG units (CpG unit 1, 2, 3, 4, 5, 6, 9 and 12) in MAGE-D4 core promoter showed hypomethylated in glioma and the methylation level of CpG unit 6 was positively associated with the prognosis of glioma patients. Furthermore, the methylation level of CpG unit 1 and 6 was negative negatively correlated with MAGE-D4 mRNA expression. Then, the results demonstrated that the promoter activity of MAGE-D4 was decreased by methylation in glioma cell lines. In addition, SP1 can binds directly to the MAGE-D4 promoter leading to up-regulation of MAGE-D4 mRNA through activation of its promoter. Finally, demethylation of MAGE-D4 promoter could benefit the SP1 binding and resulting co-activation of MAGE-D4 promoter by demethylation and SP1 in glioma cell lines. CONCLUSION: These findings indicate that the synergies of promoter hypomethylation and SP1 up-regulated MAGE-D4 transcription in glioma, which implies a potential approach to resolve the heterogeneous expression of MAGE-D4 in order to establish foundation for the MAGE-D4 based glioma therapy.

Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma.

Cancer testis (CT) antigens have received particular attention in cancer immunotherapy. OY-TES-1 is a member of CT antigens. This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma (HCC). OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR (RT-PCR). Of the 56 cases of HCC tissues tested, 37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR. OY-TES-1 protein was subsequently observed on a panel of tissue microarrays. Sera from patients were tested for OY-TES-1 antibody by ELISA. To identify OY-TES-1 capable of inducing cellular immune response, OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro. The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56 (73.21%) HCC tissues, whereas none in 5 normal liver tissues. OY-TES-1 mRNA was frequently expressed not only in HCC tissues (72.97%, 27/37), but also in paired adjacent non-cancer tissues (64.86%, 24/37). But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues (0.76854 vs. 0.09834, P=0.021). Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues, and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues. Seropositivity was detected in 10 of the 45 HCC patients, but not detected in 17 cirrhosis patients and 76 healthy donors. The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2+ HCC cell line which expressed OY-TES-1. The target lysis was mainly HLA class I -dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule. In summary, OY-TES-1 expression is up-regulated in HCC tissues and can be recognized by humoral and cellular responses, which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

Isolated Intracranial Myeloid Sarcoma Mimicking Malignant Lymphoma: A Diagnostic Challenge and Literature Reviews.

Isolated intracranial myeloid sarcoma (MS) is an unusual variant tumor with few cases reported so far in the medical literature. A 29-year-old woman was admitted to our hospital presenting progressive visual loss in the right eye and weight loss (20 kg) without a previous history of hematological disease (HD). Radiologic evaluation showed the evidence of intracranial mass. Histologically, the resected tumor was composed of a uniform population of primitive cells and primarily misdiagnosed as a T-cell non-Hodgkin's lymphoma (NHL). Chemotherapy with cyclophosphamide, doxorubicin, vinblastine, and prednisone (CHOP) was ineffective. A biopsy and histopathological evaluation were repeated, and immunohistochemical staining revealed the positivity of immature cells to an extensive panel of myeloid markers. These findings were consistent with a diagnosis of MS and bone marrow infiltration. Literature reviews of previous cases were also undertaken.

[Expression of MiR-429 in Patients with Acute Lymphoblastic Leukemia and Its Prognostic Value].

OBJECTIVE: To analyze the expression level of miR-429 in patients with acute lymphoblastic leukemia(ALL) and its clinical prognostic value. METHODS: One hundred and Twenty-six patients with ALL treated in our hospital from April 2016 to February 2018 were selected, and 100 healthy persons in the same period were selected as control group. Bone marrow mononuclear cells were collected. The expression level of miR-429 in bone marrow mononuclear cells was detected by RT-PCR, and the correlation of miR-429 expression with clinical characteristics and therapeutic efficacy was analyzed. Kaplan-Meier method and multi-factorial Cox regression model were used to analyze the correlation between the level of microRNA-429 and the prognosis of ALL patients. RESULTS: The relative level of miR-429 in ALL patients was 2.47±0.07, which was signifi-cantly higher than that in control group (P<0.05). The level of miR-429 significantly correlated with the leucocyte level（r=0.994）, LDH（r=0.992）, the ratio of bone marrow primordial cells（r=0.995） and risk grade of ALL patients（r=0.991). The level of miR-429 not correlate with the age, sex, Hb level, Plt level and immunophenotype of ALL patients (P>0.05). The level of miR-429 was not significantly different between CR patients and control group (P>0.05); the level of miR-429 in PR patients was higher than that in control group and CR patients (P<0.05). The level of miR-429 in NR patients was higher than that in other groups (P<0.05). Kaplan-Meier survival analysis showed that the overall survival rate of ALL patients with low expression of miR-429 was better than that of ALL patients with high expression of miR-429 (P<0.05). Univariate Cox regression analysis showed that leukocyte level, ratio of bone marrow primordial cells, Hb and LDH level, risk grading and miR-429 were the factors influencing overall survival rate in ALL patients (P<0.05). Multivariate Cox regression analysis showed that leukocyte level, ratio of bone marrow primordial cells, risk grading, and miR-429 were the factors influencing overall survival rate (P<0.05). CONCLUSION: The expression of miR-429 is high in ALL patients, which closely relates to the curative effect and pro-gnosis of ALL patients, and can be used as a reference index for evaluation of clinical prognosis of ALL patients.

Correlation between adiponectin, chemerin, vascular endothelial growth factor and epicardial fat volume in patients with coronary artery disease.

Epicardial fat, a local visceral fat depot surrounded by visceral pericardial sac, surrounds the coronary arteries for most of their course and may contribute to the development of coronary atherosclerosis by local production of inflammatory cytokines. Some studies on non-invasive measurement of epicardial fat mass have shown that epicardial fat mass is associated with the increased incidence of coronary artery disease (CAD), onset and progression of coronary plaque, mainly including major adverse cardiovascular events, myocardial ischemia, and atrial fibrillation. In the present study the correlation of adiponectin, chemerin, and vascular endothelial growth factor (VEGF) with the epicardial fat volume in patients with coronary artery disease was explored, and the risk factors for vascular remodeling of CAD patients were analyzed. A total of 50 CAD patients, treated in Chongzuo People's Hospital from August 2017 to September 2018, were enrolled as the observation group, and further 50 healthy individuals, who underwent physical examinations in the hospital at the same period, were enrolled as the control group. RT-qPCR was adopted to detect the expression levels of adiponectin, chemerin and VEGF in the two groups, a 64-slice dual-source CT to detect epicardial fat volume, and Pearson's correlation to analyze adiponectin, chemerin, VEGF and epicardial fat volume. Logistic regression analysis was performed to analyze the risk factors for vascular remodeling in CAD patients, and a receiver operating characteristic (ROC) curve analysis was used to analyze the value of indexes with multifactorial significance in vascular remodeling. The observation group showed obviously larger epicardial fat volume than the control group (P<0.001), lower adiponectin expression than the control group (P<0.001), and higher chemerin and VEGF expression than the control group (P<0.001). In the observation group, adiponectin expression decreased with the increase of epicardial fat volume (P<0.001), while the expression of chemerin and VEGF increased with the increase of epicardial fat volume (P<0.001). Remodeling occurred in 27 of the 50 patients. ROC curve analysis showed that the areas under the curves of adiponectin, chemerin, VEGF and epicardial fat volume were 0.697, 0.652, 0.696 and 0.689, respectively. Epicardial fat volume, adiponectin, chemerin and VEGF are independent risk factors for vascular remodeling and the expression of adiponectin, chemerin and VEGF can reflect epicardial fat volume.

Ewing's sarcoma of the cervix: A case report and review of literature.

Ewing's sarcoma (ES) is a small cell malignant tumor that occurs in the bone of children or adolescents. ES can also occur in extraskeletal organs, such as the pancreas, thyroid, liver, proximal phalanx, and, rarely, cervix. Only 15 published case reports have discussed ES arising in the cervix. We report a 76-year-old woman who had groin mass. ES was diagnosed in accordance with morphological and immunohistochemical maps. Fluorescence in situ hybridization and RT-PCR (reverse transcription PCR) revealed ESWR1 gene rearrangement and fusion gene formation (EWS-FLI-1), both of which confirmed the diagnosis of ES. Although the patient underwent surgical resection, the patient died without chemotherapy and radiotherapy. This case is the first one to involve a patient aged over 70 years and the fifth one to show metastasis occurrence.

Expression profile of ACTL8, CTCFL, OIP5 and XAGE3 in glioma and their prognostic significance: a retrospective clinical study.

BACKGROUND: Cancer/testis antigens (CTAs) are attractive therapeutic targets for tumor immunotherapy due to their restrictive expression in normal testis but excessive in majority of tumor types. ACTL8, CTCFL, OIP5 and XAGE3 are members of the CTAs family. Currently, the data of ACTL8, CTCFL, OIP5 and XAGE3 expression in glioma is limited. Methods: ACTL8, CTCFL, OIP5 and XAGE3 mRAN and protein expressions were detected in 108 glioma samples by Reverse Transcriptase-PCR (RT-PCR) and immunohistochemistry and the correlations between their expressions and clinical indexes were analyzed. Furthermore, their clinical significance on glioma prognosis was determined by follow-up data. Results: The mRNA positive rate of ACTL8, CTCFL, OIP5 and XAGE3 was 15.74% (17/108), 22.22% (24/108), 13.89% (15/108) and 37.96% (41/108), respectively. At least one CTA mRNA was expressed by 61.11% of glioma tissues, while 2 or more by 29.63%. For protein expression, the positive rate of them was 21.30% (23/108), 34.26% (37/108), 19.44% (21/108) and 23.15% (25/108), respectively. At least one CTA protein was expressed by 58.33% of glioma tissues and 2 or more by 29.63%. Although there were no correlations between their mRNA expressions and clinicopathological parameters, the protein expression of ACTL8, OIP5 and XAGE3 was positively correlated with KPS; while the ACTL8 protein was correlated with gender, and OIP5 protein with gender and WHO grade. Kaplan-Meier analysis revealed a significant negative correlation between the CTCFL protein expression, combined ACTL8 and/or CTCFL protein expression and survival. Conclusions: The results suggest that the cohort of glioma does express ACTL8, CTCFL, OIP5 and XAGE3 at both mRNA and protein levels indicating glioma is CTAs-rich tumors. CTCFL protein and the combined ACTL8 and/or CTCFL protein might act as poor prognostic markers for glioma and as potential ideal combined antigens for glioma immunotherapy.