Prognostic factors analysis of diffuse midline glioma.

PURPOSE: This study retrospectively analyzes cases of diffuse midline glioma treated with radiotherapy, with the aim of investigating the prognosis of the tumor and its influencing factors. METHODS: From January 2018 to November 2022, we treated 64 patients who were pathologically diagnosed with diffuse midline glioma. Among them, 41 underwent surgical resection, and 23 underwent biopsy procedures. All patients received postoperative radiotherapy. We followed up with the patients to determine the overall survival rate and conducted univariate and multivariate analyses on relevant indicators. RESULTS: The median survival time for the entire patient group was 33.3 months, with overall survival rates of 92.9%, 75.4%, and 45.0% at 1 year, 2 years, and 3 years, respectively. Univariate and multivariate analyses indicated that older patients had a better prognosis. CONCLUSION: Patient age is an independent prognostic factor for patients with diffuse midline glioma undergoing radiation therapy.

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.

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.

The Impostor Phenomenon Among Nursing Students and Nurses: A Scoping Review.

The impostor phenomenon (IP) refers to a false internal experience of low intelligence or ability that is associated with anxiety, depression, psychological distress, and burnout. The emotions associated with the IP affect not only personal mental health but also patient care. To address this issue, we need to completely understand the prevalence of and factors related to the IP and ways to resolve/overcome IP feelings. The aim of this scoping review was to identify the existing evidence regarding the IP among nursing students and nurses and determine gaps that can be addressed in future research. We conducted our study based on the scoping review methodological framework proposed by Arksey and O'Malley (2005) and advanced by Levac et al. (2010). After searching the Embase, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, Web of Science and ProQuest databases, we identified 11 studies for inclusion in this review. We found that while the IP exists in nursing students and nurses, clinical nurse specialist students and final-year nursing students are at significant risk of impostor behavior. We also found that research in the nursing field has focused on the prevalence of and factors related to the IP, but few studies have addressed ways to resolve/overcome IP feelings. Thus, research in this area should be increased. This scoping review presents research gaps that may serve as a starting point for future work on the IP in the nursing field.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Identification of Dysregulated microRNAs in Glioma Using RNA-sequencing.

Glioma is the most common malignant brain tumor in central nervous system. Despite advances in the treatment of glioma such as surgery and chemoradiotherapy, most patients are easy to relapse, resulting in adverse clinical outcomes. Hence, effective molecular-targeting treatment may be one of attractive strategies for glioma therapy. The dysregulated microRNAs (miRNAs), one of the candidates of therapeutic targets, are believed to play an important role in the progression of glioma. In this study, we aimed to examine the expression profile of miRNAs in glioma and provide a reference for glioma therapy. Firstly, expression profile of miRNAs in 5 normal brain tissues, 5 low-grade glioma (LGG) tissues and 5 glioblastoma (GBM) tissues was detected by RNA sequencing (RNA-seq). Next, the target genes of differentially expressed miRNAs (DEmiRNAs) were predicted and then GO enrichment and KEGG pathway analysis performed by bioinformatics. Finally, 10 miRNAs which were significantly up- or down-regulated both in GBM and LGG were validated by real-time quantitative PCR (qRT-PCR). RNA-seq results indicated a number of DEmiRNAs in glioma. There were 64 up-regulated miRNAs and 17 down-regulated miRNAs in LGG, and 181 up-regulated miRNAs and 124 down-regulated miRNAs in GBM, respectively. Bioinformatics analysis showed that the target genes of these DEmiRNAs were enriched in various biological processes and signaling pathways such as cell metabolic and developmental process. Selected DEmiRNAs were further confirmed by qRT-PCR. miRNA-10b-5p, miRNA-92b-3p and miRNA-455-5p were significantly up-regulated in both GBM and LGG; while miRNA-542-3p was significantly up-regulated in LGG; miRNA-184 and miRNA-206 were significantly down-regulated in both GBM and LGG; miRNA-766-5p and miRNA-1-3p were significantly down-regulated in GBM. The subject of our study demonstrated several dysregulated miRNAs may serve as a potential therapeutic target for glioma.

ABC Transporters in Prorocentrum lima and Their Expression Under Different Environmental Conditions Including Okadaic Acid Production.

Prorocentrum lima is a typical benthic toxic dinoflagellate, which can produce phycotoxins such as okadaic acid (OA). In this study, we identified three ABC transporter genes (ABCB1, ABCC1 and ABCG2) and characterized their expression patterns, as well as OA production under different environmental conditions in P. lima. We found that the three ABC transporters all showed high identity with related ABC proteins from other species, and contained classical features of ABC transport proteins. Among them, ABCG2 was a half size transporter. The three ABC transporter genes displayed various expression profiles under different conditions. The high concentration of Cu2+ could up-regulate ABCB1, ABCC1 and ABCG2 transcripts in P. lima, suggesting the potential defensive role of ABC transporters against metal ions in surrounding waters. Cu2+, in some concentration, could induce OA production; meanwhile, tributyltin inhibited OA accumulation. The grazer Artemia salina could induce OA production, and P. lima displayed some toxicity to the grazer, indicating the possibility of OA as an anti-grazing chemical. Collectively, our results revealed intriguing data about OA production and the expression patterns of three ABC transporter genes. However, we could not find any significant correlation between OA production and expression pattern of the three ABC transporters in P. lima. Our results might provide new molecular insights on the defensive responses of P. lima to the surrounding environment.

Involvement of X-chromosome Reactivation in Augmenting Cancer Testis Antigens Expression: A Hypothesis.

Cancer testis antigens (CTAs) are attractive targets for tumor immunotherapy because of their tumor-specific expression. Since more than half of confirmed CTAs are located on the X-chromosome, we asked whether there is a link between CTA expression and X-chromosomes. Recent reports have shown that reactivation of the inactive X-chromosome, known as X-chromosome reactivation (XCR), a unique phenomenon that exists in many high-risk tumors in women, can transform the expression of many X-linked genes from monoallelic to biallelic. In this review, we discuss the link between CTA and XCR with the hopes of providing some novel insights into tumor biology.

Prognostic and clinicopathological value of melanoma-associated antigen D4 in patients with glioma.

The aim of the present study was to evaluate the clinical importance of melanoma-associated antigen D4 (MAGE-D4) expression in glioma, and to identify it as a valuable prognostic biomarker and therapeutic target. To achieve this, the expression of MAGE-D4 protein in 124 tumor tissues from patients with glioma was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC), and the associations between MAGE-D4expression and clinicopathological factors were evaluated. The survival analysis demonstrated the significant prognostic value of MAGE-D4 in glioma using follow-up data. RT-qPCR and IHC analysis confirmed that MAGE-D4 mRNA and protein expression levels were significantly increased in glioma tissues compared with those in normal brain tissues. The present study demonstrated that the percentage of glioma tissues with high expression of MAGE-D4 mRNA was 67.74%, and the percentage positive for MAGE-D4 protein expression was 78.23%. All patients with high MAGE-D4 expression in cancerous tissues experienced significantly reduced median overall survival (OS; 18.00 vs. 33.29 months; P<0.001) and recurrence-free survival (RFS; 12.7 vs. 28.3 months; P<0.001) times compared with those with low MAGE-D4 expression. In the patients with lower grade glioma [World Health Organization (WHO), I-II], similar results were obtained for the OS (26.11 vs. 57.85 months; P=0.013) and RFS (22.7 vs. 55.3 months; P=0.010) times; however, in patients with high-grade glioma (WHO, III-IV), there were no significant differences between high and low MAGE-D4 expression levels with regard to OS and RFS times (P>0.05). Multivariate analysis indicated that high MAGE-D4 protein expression was an important independent prognostic factor for patients with glioma (hazard ratio, 2.384; P=0.005), and was significantly associated with higher grade glioma (P<0.001). These results indicated that MAGE-D4 may be a potential biomarker for glioma and an important prognostic factor for patients with new or recurring glioma.

Recombinant Adenovirus-p53 Gene Therapy for Advanced Unresectable Soft-Tissue Sarcomas.

Patients with unresectable advanced soft-tissue sarcomas (STS) receiving radiotherapy or/and chemotherapy still have a poor prognosis. This study aimed to evaluate retrospectively the efficacy and safety of recombinant adenovirus-p53 (rAd-p53) gene therapy combined with radiotherapy and hyperthermia for advanced STS. A total of 71 patients with advanced unresectable STS treated at the authors' center from April 2007 to November 2014 were included. Of these 71 patients, 36 cases received rAd-p53 therapy combined with radiotherapy and hyperthermia (p53 group), while 35 cases received radiotherapy and hyperthermia alone (control group). Short-term therapeutic efficacies, long-term survival outcomes, and adverse events were evaluated and compared between groups. Compared to the control group, the p53 group had a significantly higher disease control rate (83.33% vs. 54.29%; p = 0.008) and a lower progressive disease rate (16.67% vs. 45.71%; p = 0.018). In addition, rAd-p53 treatment significantly improved the progression-free survival and overall survival of STS patients. Cox regression indicated that rAd-p53 treatment significantly reduced the risks for disease progression or death event for STS patients. Furthermore, there was no significant difference in all adverse events, except for transient fever, which occurred in 89% of patients with rAd-p53 therapy. rAd-p53 combined with radiotherapy and hyperthermia can effectively improve the therapeutic efficacy and survival outcomes in patients with advanced unresectable STS, providing a new therapeutic strategy.

Nonmissile Penetrating Head Injuries: Surgical Management and Review of the Literature.

BACKGROUND: Nonmissile penetrating head injuries (NPHIs) in the civilian population are rare but potentially fatal. Although numerous cases have been reported in the literature, the surgical management of such injuries is still ambiguous, especially with development of surgical techniques. Here, we report 5 cases of NPHIs managed with different surgical techniques and review the literature on surgical treatment of these injuries to outline the appropriate management for these patients from a neurosurgical perspective. METHODS: We retrospectively reviewed 5 cases of NPHIs managed surgically in our department. The clinical data were collected, including cause, type of objects, way of penetration, initial clinical evaluation, imaging, surgical intervention, postoperative care, complication, follow-up, and outcome. In addition, a systematic review of the literature was performed in the PubMed database to search for articles on surgical treatment of these injuries. RESULTS: These 5 cases were caused by twisted steel bar, electric welding rod, and sewing needle, respectively. Preoperative imaging, including computed tomography, magnetic resonance imaging, and digital subtraction angiography, was selectively performed to assist the operative plan. Foreign objects were removed surgically in all cases. Postoperative prophylactic administration of antibiotics and anticonvulsants was used to prevent infectious and epileptic complications. Most of the patients achieved a better outcome except for one. CONCLUSIONS: NPHIs can be fatal but they can be managed with satisfactory results by proper preoperative imaging evaluation, rapid appropriate surgical management, and accurate postoperative care. Personalized surgical intervention should be undertaken depending on the mechanism and extent of the NPHI.

Effect and Safety of Recombinant Adenovirus-p53 Transfer Combined with Radiotherapy on Long-Term Survival of Locally Advanced Cervical Cancer.

Detection of exogenous p53 gene and target gene expression in cervical cancer cell lines SiHa and C33A infected by recombinant adenovirus-p53 (rAd-p53) in vitro. The rAd-p53 infection evidently increased the expression of exogenous p53 gene, p21 gene, and Bax gene. The radiosensitization rates of rAd-p53 were 1.19 in SiHa and 1.18 in C33A in vitro. To evaluate the effect and safety of rAd-p53 transfer combined with radiotherapy (RT) in patients with cervical cancer, rAd-p53 transfer combined with radiotherapy (group PRT) in 69 patients with cervical cancer was compared with a control group treated with radiotherapy alone (group RT) in 35 patients with cervical cancer. Patients were intratumorally injected with rAd-p53 (1 × 1012 virus particles) once a week for 6 weeks. Concurrent pelvic RT plus brachytherapy to take point A to 76.0 Gray units (Gy) (range 75-80 Gy). The 5-year overall survival rate of the PRT group was 17.5% higher than that of the RT group (HR = 0.551, 95% CI 0.278-1.095, p = 0.084). The 5-year progress-free survival rate of the PRT group was 17.1% higher than that of the RT group (HR = 0.485, 95% CI 0.234-1.006, p = 0.047). rAd-p53 administration did not increase the adverse events caused by radiotherapy, except for transient fever after rAd-p53 administration. rAd-p53 was safe and biologically active in improving radiotherapeutic survival rates in patients with cervical cancer.

Down-regulation of cancer/testis antigen OY-TES-1 attenuates malignant behaviors of hepatocellular carcinoma cells in vitro.

Cancer/testis (CT) antigens are normally expressed in testis and overexpressed in various tumor types. However, their biological function is largely unknown. OY-TES-1, one of cancer/testis (CT) antigens, is reported overexpression in hepatocellular carcinoma (HCC). And we assumed that OY-TES-1 contribute to oncogenesis and progression of HCC. In this study, we knocked down OY-TES-1 by small interference RNA (siRNA) in HCC cell lines (HepG2 and BEL-7404) to verify this assumption and evaluate its potential as therapeutic targets for HCC. We showed that down regulation of OY-TES-1 decreased cell growth, induced the G0/G1 arrest and apoptosis, and prevented migration and invasion in the two HCC cell lines. Further analysis revealed that down regulation of OY-TES-1 increased expression of apoptosis-regulated protein caspase-3, and decreased expression of cell cycle-regulated protein cyclin E, migration/invasion-regulated proteins MMP2 and MMP9. These findings may shed light on the gene therapy about the OY-TES-1 expression in HCC cells.

Outcome and complications of endovascular embolization for vein of Galen malformations: a systematic review and meta-analysis.

OBJECT: There have been many multidisciplinary approaches to the treatment of vein of Galen malformations. Endovascular embolization is the first option for treatment. However, the effects of the treatment remain controversial. The aim of this study is to assess the efficacy and safety of endovascular embolization to treat patients with vein of Galen malformations. METHODS: This paper includes a retrospective analysis of a sample of 667 patients who underwent endovascular embolization to treat vein of Galen malformations. The data were obtained through a literature search of PubMed databases. The authors also evaluate the efficacy and safety of the treatment. Mortality within the follow-up period is analyzed. Pooled estimates of proportions with corresponding 95% CIs were calculated using raw (i.e., untransformed) proportions (PRAW). RESULTS: In the 34 studies evaluated, neonates accounted for 44% of the sample (95% CI 31%-57%; I(2) = 92.5%), infants accounted for 41% (95% CI 30%-51%; I(2) = 83.3%), and children and adults accounted for 12% (95% CI 7%-16%; I(2) = 52.9%). The meta-analysis revealed that complete occlusion was performed in 57% (95% CI 48%-65%; I(2) = 68.2%) of cases, with partial occlusion in 43% (95% CI 34%-51%; I(2) = 70.7%). The pooled proportion of patients showing a good outcome was 68% (95% CI 61%-76%; I(2) = 77.8%), while 31% showed a poor outcome (95% CI 24%-38%; I(2) = 75.6%). The proportional meta-analysis showed that postembolization mortality and complications were reported in 10% (95% CI 8%-12%; I(2) = 42.8%) and 37% (95% CI 29%-45%; I(2) = 79.1%), respectively. Complications included cerebral hemorrhage, cerebral ischemia, hydrocephalus, leg ischemia, and vessel perforation. CONCLUSIONS: The successful treatment of vein of Galen malformations remains a complex therapeutic challenge. The authors' analysis of clinical history and research literature suggests that vein of Galen malformations treated with endovascular embolization can result in an acceptable mortality rate, complications, and good clinical outcome. Future large-scale, multicenter, randomized trials are necessary to confirm these findings.

Intracranial meningioma surgery in the elderly (over 65 years): prognostic factors and outcome.

BACKGROUND: Meningiomas are more prevalent in elderly individuals; however, the surgical outcome and prognostic factors in this age group are unclear. This retrospective study aimed to identify the prognostic factors of elderly patients with intracranial meningiomas who underwent surgical resection. METHODS: Eighty-six patients (aged ≥ 65) diagnosed with an intracranial meningioma were surgically treated at our department. The clinical, radiological, and follow-up data were retrospectively reviewed. Univariate and multivariate logistic analyses were performed to identify relationships between factors [age, sex, neurological condition, concomitant disease, American Society of Anesthesiology (ASA) classification, preoperative Karnofsky Performance Scale (KPS) score, tumor location and size, peritumoral edema, and Simpson resection grade] and outcome. RESULTS: One patient (1.2 %) died within 30 days of surgery. The morbidity rate was 37.2 %. Postoperative morbidities occurred more frequently in the patients with preoperative neurological deficits than in those without (p = 0.049). Univariate analysis identified significant relationships between a low KPS score (≤ 70) at discharge and preoperative neurological deficits, low preoperative KPS score (≤ 70), and critical tumor location (p < 0.001, p < 0.001, and p = 0.04, respectively). In the multivariate logistic analysis, only the preoperative KPS score remained significant for the KPS score at discharge (p = 0.005); there was no significant association with the most recent KPS score. CONCLUSION: The outcome of intracranial meningioma resection in elderly individuals is favorable if the preoperative KPS score is >70 and no neurological deficits are present. Treatment decisions should be patient-specific, and additional factors should be considered when operations are performed in patients with a low preoperative KPS score or neurological deficits.

Decompressive hemicraniectomy in patients with malignant middle cerebral artery infarction: A systematic review and meta-analysis.

BACKGROUND & PURPOSE: Malignant middle cerebral artery infarctions (mMCAI) are one of the most devastating ischemic strokes, with up to 80% mortality in non-surgically treated patients. With the publication of three European randomized controlled trials (RCTs), decompressive hemicraniectomy (DHC) was recommended in patients with mMCAI who are aged ≤ 60 years. Recently, three other RCTs enrolling patients aged > 60 years were published; thus, it is necessary to update the previous meta-analysis to re-evaluate the effects of DHC in mMCAI. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library was conducted for published RCTs investigating the effects of DHC in mMCAI. Primary outcomes were mortality and major disability (modified Rankin Scale score: 4-5) among survivors. Secondary outcomes were death or major disability (mRS score > 3), and death or severe disability (mRS score > 4). Effect sizes were expressed in Peto odds ratio (Peto OR) with 95% confidence intervals. RESULTS: Six studies with 314 patients were subjected to meta-analysis. Data showed that DHC, significantly decreased mortality risk, death or major disability (mRS score > 3), and death or severe disability (mRS score > 4); but was associated with a slightly higher proportion of major disability (mRS score: 4-5) among survivors. There were no statistically significant age differences. CONCLUSIONS: Compared to conservative treatment, DHC significantly decreased mortality and improved functional outcome, with a non-significant increase in the proportion of survivors with major disability. Further studies are required for multidimensional evaluation of DHC for mMCAI.

Overexpression of MAGE-D4 in colorectal cancer is a potentially prognostic biomarker and immunotherapy target.

Melanoma-associated antigen D4 (MAGE-D4) is a novel member of MAGE family. This study aimed to examine the expression and immunogenicity of MAGE-D4 in colorectal cancer (CRC) to determine its potential as a prognosis and immunotherapeutic target. The expression of MAGE-D4 mRNA and protein was determined by RT-PCR and immunohistochemistry (IHC) in CRCs with paired adjacent non-tumor tissues, colorectal adenomas and normal colorectal tissues, respectively. Sera from 64 CRC patients were tested for MAGE-D4 antibody by ELISA. MAGE-D4 mRNA was more frequently expressed in CRCs (76.7%, 46/60) than in adjacent non-tumor tissues (15.0%, 9/60). MAGE-D4 protein was detected in all the CRC tissues tested, 70.0% of which showed high expression. There was no MAGE-D4 protein detected in any paired adjacent non-tumor tissue. No MAGE-D4 expression was found in colorectal adenomas and normal colorectal tissues by either RT-PCR or immunohistochemistry. Patients with high MAGE-D4 protein expression had significantly shorter overall survival than those with low MAGE-D4 protein expression (median, 68.6 vs 122.2 months; P=0.030). Furthermore, multivariate analysis exhibited high MAGE-D4 protein expression had a trend toward an independent prognostic factor (hazard ratio: 6.124; P=0.050). Humoral immunity to MAGE-D4 was detected in 12 of 64 (18.8%) CRC patients' sera but not in 77 healthy donors. There was no correlation between MAGE-D4 expression, serum antibody and clinicopathological parameters. These findings suggest MAGE-D4 may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in CRC.

High expression and frequently humoral immune response of melanoma-associated antigen D4 in glioma.

MAGE-D4 is a novel member of MAGE super-family. It has preliminarily been demonstrated that MAGE-D4 mRNA is not expressed in majority of normal tissues except for brain and ovary in which only trace amount of MAGE-D4 mRNA can be detected, but predominantly expressed in glioma. MAGE-D4 protein expression and its immunogenicity in glioma have not been elucidated well. This study was designed to analyze MAGE-D4 expression both at mRNA and protein level, characteristic of humoral immune response, and their relationships with glioma patients' clinicopathological parameters. Recombinant MAGE-D4 protein and antiserum were generated. Quantitative RT-PCR analysis revealed that MAGE-D4 mRNA expression was overall up-regulated in 41 glioma specimens compared with that in 14 normal brain tissues. Immunohistochemistry analysis showed that 78% (21/27) glioma tissues expressed MAGE-D4 protein, which was predominantly located in the cytoplasm of tumor cells, but absent in any neuroglia cell of normal brain tissues. ELISA analysis demonstrated that humoral response against MAGE-D4 was detected in 17% (7/41) of glioma patients' sera but not in 77 healthy donors. No apparent correlation was observed between the expression and immunogenicity of MAGE-D4 with clinicopathological parameters of glioma. In summary, these results indicate that MAGE-D4 is highly expressed in glioma and can develop specifically humoral response in glioma patients, which supports that it may be a promising biomarker for glioma diagnosis and immunotherapy.

MAGED4 expression in glioma and upregulation in glioma cell lines with 5-aza-2'-deoxycytidine treatment.

Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.