Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r²=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.
Adolescent ; Adult ; Brain Neoplasms/pathology* ; Central Nervous System/pathology* ; Central Nervous System Neoplasms/metabolism* ; Child ; Child, Preschool ; China ; Female ; Germinoma/pathology* ; Histones ; Humans ; Male ; Middle Aged ; Neoplasms, Germ Cell and Embryonal/diagnosis* ; Oncogene Proteins ; Transcription Factors/metabolism* ; Young Adult

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.
Brain Neoplasms ; Glioblastoma ; Glioma/diagnosis* ; Glutathione Peroxidase/metabolism* ; Humans ; Peroxidases ; Prognosis ; Proportional Hazards Models

Glioblastoma (GBM) can be classified into molecular subgroups, on the basis of biomarker expression. Here, we classified our cohort of 163 adult GBMs into molecular subgroups according to the expression of proteins encoded by genes of alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase (IDH) and TP53. We focused on the survival rate of molecular subgroups, depending on each and various combination of these biomarkers. ATRX, IDH1 and p53 protein expression were evaluated immunohistochemically and Kaplan-Meier analysis were carried out in each group. A total of 15.3% of enrolled GBMs demonstrated loss of ATRX expression (ATRX-), 10.4% expressed an aberrant IDH1 R132H protein (IDH1+), and 48.4% exhibited p53 overexpression (p53+). Survival differences were statistically significant when single protein expression or different combinations of expression of these proteins were analyzed. In conclusion, in the case of single protein expression, the patients with each IDH1+, or ATRX-, or p53- GBMs showed better survival than patients with counterparts protein expressed GBMs. In the case of double protein pairs, the patients with ATRX-/p53-, ATRX-/IDH1+, and IDH1+/p53- GBMs revealed better survival than the patients with GBMs with the remained pairs. In the case of triple protein combinations, the patients with ATRX-/p53-/IDH+ showed statistically significant survival gain than the patients with remained combination of proteins-expression status. Therefore, these three biomarkers, individually and as a combination, can stratify GBMs into prognostically relevant subgroups and have strong prognostic values in adult GBMs.
Adult ; Aged ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/*diagnosis/metabolism/mortality ; DNA Helicases/*metabolism ; Disease-Free Survival ; Glioblastoma/*diagnosis/metabolism/mortality ; Humans ; Immunohistochemistry ; Isocitrate Dehydrogenase/*metabolism ; Kaplan-Meier Estimate ; Middle Aged ; Nuclear Proteins/*metabolism ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics/*metabolism ; Young Adult

OBJECTIVETo discuss the clinicopathologic features of rhabdoid glioblastoma of the brain and its differential diagnoses.

METHODSA 10-year-old and a 45-year-old female both presented with gradually worsening headache, limbs twitch and blurred vision. MRI scan revealed a contrast enhancing tumor in the right temporal lobe and left cerebellum respectively. Both patients underwent tumor resection, followed by postoperative radiotherapy and chemotherapy.

RESULTSMicroscopic examination of both tumors showed rhabdoid tumor cells with an eccentric nuclei and eosinophilic cytoplasms. Both tumors had areas of classic glioblastoma with microvascular proliferation and necrosis. Immunohistochemical staining showed the rhabdoid tumor cells were positive for vimentin diffusely and GFAP, EMA, CK focally. Integrase interactor (INI-1) was expressed in most tumor cells, but IDH1 R132H was not detected in both tumors. Fluorescence in situ hybridization revealed 1p/19q co-deletion in one case. One patient was alive without tumor recurrence after 16 months follow-up, the other patient died of intraspinal tumor dissemination 9 months after surgery.

CONCLUSIONSRhabdoid glioblastoma is a rare glial cell tumor with specific rhabdoid tumor cells, a highly aggressive clinical course and poor prognosis. Combining histological features, a panel of selected immunostains including vimentin, GFAP, CK, EMA, SMA and INI-1 is helpful in making an accurate diagnosis for those diagnostically challenging cases with rhabdoid features in central nervous system.

Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; pathology ; Child ; Diagnosis, Differential ; Female ; Glioblastoma ; pathology ; Humans ; In Situ Hybridization, Fluorescence ; Magnetic Resonance Imaging ; Middle Aged ; Necrosis ; Neoplasm Recurrence, Local ; Rhabdoid Tumor ; pathology ; Temporal Lobe ; pathology

OBJECTIVETo study the clinicopathologic features of papillary tumor of the pineal region (PTPR).

METHODThree hundred and eighty six cases of pineal region and posterior third ventricle tumors, two newborn and two adult pineal glands were analyzed by HE, PAS and immunohistochemistry of 16 antibodies (EnVision method).

RESULTSFive cases of PTPR were diagnosed with mixed papillary features and densely cellular areas, and included one recurrent case. In the papillary areas, the vessels were lined by one or several layers of cuboidal/columnar cells; the vessel wall was hyalinized. In the densely cellular areas, sheets or nests of tumor cells were seen. The tumor cells of these five cases were immunoreactive to CK, CK8/18, synaptophysin, MAP2, nestin, S-100, and vimentin. Four cases were immunoreactive to NSE and CgA; and 2 cases were immunoreactive to NF. All five cases were negative for EMA, CK5/6, CEA, and NeuN. Ki-67 labeling index ranged from 1% to 6%.Three patients were alive, and the recurrent one died.

CONCLUSIONSPTPR occurs in patients with over a wide age range, from children to adults, and is more commonly found in male than female. PTPR is composed of both papillary and solid areas, characterized by epithelial cytology, and needs to be differentiated from ependymoma. PTPR may originate from the specialized ependymocytes of the subcommissural organ. The prognostic factors are early diagnosis, complete surgical resection and radiotherapy.

Adolescent ; Adult ; Brain Neoplasms ; diagnostic imaging ; metabolism ; pathology ; radiotherapy ; surgery ; Carcinoma, Papillary ; diagnostic imaging ; metabolism ; pathology ; radiotherapy ; surgery ; Child ; Diagnosis, Differential ; Ependymoma ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Keratin-18 ; metabolism ; Keratin-8 ; metabolism ; Keratins ; metabolism ; Male ; Microtubule-Associated Proteins ; metabolism ; Nestin ; metabolism ; Pineal Gland ; Pinealoma ; metabolism ; pathology ; S100 Proteins ; metabolism ; Synaptophysin ; metabolism ; Tomography, X-Ray Computed ; Vimentin ; metabolism ; Young Adult

Adenoma ; pathology ; Brain Neoplasms ; secondary ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Pituitary Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Reoperation ; Synaptophysin ; metabolism ; Temporal Lobe ; pathology

Brain Neoplasms ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Neoplasm Recurrence, Local ; Nestin ; metabolism ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; surgery ; Temporal Lobe ; Vimentin ; metabolism

Adenocarcinoma ; diagnosis ; metabolism ; pathology ; secondary ; Brain ; metabolism ; pathology ; Brain Neoplasms ; diagnosis ; metabolism ; pathology ; secondary ; Carcinoembryonic Antigen ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Keratin-7 ; metabolism ; Lung Neoplasms ; pathology ; Magnetic Resonance Imaging ; Middle Aged ; Nuclear Proteins ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

OBJECTIVESTo analyze the long-term survivors of glioblastoma and to identify any prognostic factors that potentially contribute to survival.

METHODSFifteen glioblastomas patients underwent surgery from June 2007 to April 2009 who survived longer than 3 years were enrolled in. Clinical characteristics such as age, location of tumor, extent of resection, and radiotherapy or chemotherapy were analyzed. The expressions of epidermal growth factor receptor (EGFR), tumor protein 53 (P53), phosphatase and tensin homolog (PTEN), O6-methylguanine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 gene (IDH1), and neurofibromatosis type 1 (NF-1) in tumor samples were measured by immunohistochemical method, and the status of P53 and IDH1 were detected by direct DNA sequencing as well. And the patients who survived less than 1 year were set as control. Kaplan-Meier analysis was used to evaluate the prognostic factors.

RESULTSThe average age of patients at diagnosis was 45.6 years. And the overall survival time was 3-6 years (median survival time 3.5 years). Thirteen patients underwent a total resection, and 14 patients took orally temozolomide. The occurrence frequency of these molecular markers in long-term survivors was PTEN (13/15), IDH1 (13/15), IDH1 mutation (12/15), P53 (8/15), P53 mutation (7/15), EGFR (6/15), MGMT (4/15) and NF-1 (3/15). There was a good correlation between IDH1 protein expression and IDHI mutation, and between P53 protein expression and P53 mutation. And the survival analysis showed that age above 50 years at diagnosis (OR = 0.262, 95%CI: 0.102 - 0.672), total resection (OR = 0.372, 95%CI: 0.149 - 0.931) and combined oral temozolomide (OR = 0.131, 95%CI: 0.044 - 0.390) were favorable clinical prognostic factors. PTEN (OR = 0.201, 95%CI: 0.074 - 0.549) and IDH1 (OR = 0.151, 95%CI: 0.050 - 0.454) expression, IDH1 mutation (OR = 0.276, 95%CI: 0.108 - 0.709) in tumor cells contributed to a favorable prognosis.

CONCLUSIONSThere is probably no single molecular marker that is responsible for long-term survival of patients with glioblastoma, may be a balance between all these molecular events result in a favorable outcome.

Adult ; Brain Neoplasms ; diagnosis ; metabolism ; Female ; Glioblastoma ; diagnosis ; metabolism ; Humans ; Isocitrate Dehydrogenase ; metabolism ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Mutation ; PTEN Phosphohydrolase ; metabolism ; Prognosis ; Survivors