Xing Fan

Anatomical localization of isocitrate dehydrogenase 1 mutation: a voxel-based radiographic study of 146 low-grade gliomas

A brain tumors location is associated with the genetic profile of its tumor precursor cells. Mutations in isocitrate dehydrogenase 1 (IDH1) are an early event in tumor development and play a critical role in gliomagenesis. This study was conducted to specify the anatomical characteristics of IDH1 mutation in low‐grade gliomas and to further explore the origin of gliomas with IDH1 mutation. The impact of IDH1 mutation on disease prognosis was also evaluated.

Radiological features combined with IDH1 status for predicting the survival outcome of glioblastoma patients.

BACKGROUND Radiological characteristics may reflect the biological features of brain tumors and may be associated with genetic alterations that occur in tumorigenesis. This study aimed to investigate the relationship between radiological features and IDH1 status as well as their predictive value for survival of glioblastoma patients. METHODS The clinical information and MR images of 280 patients with histologically confirmed glioblastoma were retrospectively reviewed. The radiological characteristics of tumors were examined on MR images, and the IDH1 status was determined using DNA sequencing for all cases. The Kaplan-Meier method and Cox regression model were used to identify prognostic factors for progression-free and overall survival. RESULTS The IDH1 mutation was associated with longer progression-free survival (P = .022; hazard ratio, 0.602) and overall survival (P = .018; hazard ratio, 0.554). In patients with the IDH1 mutation, tumor contrast enhancement and peritumoral edema indicated worse progression-free survival (P = .015 and P = .024, respectively) and worse overall survival (P = .024 and P = .032, respectively). For tumors with contrast enhancement, multifocal contrast enhancement of the tumor lesion was associated with poor progression-free survival (P = .002) and poor overall survival (P = .010) in patients with wild-type IDH1 tumors. CONCLUSIONS Combining the radiological features and IDH1 status of a tumor allows more accurate prediction of survival outcomes in glioblastoma patients. The complementary roles of genetic changes and radiological features of tumors should be considered in future studies.

Anatomical specificity of O6-methylguanine DNA methyltransferase protein expression in glioblastomas

O6-methylguanine DNA methyltransferase (MGMT) is one of the important tumor-related biomarkers and is considered to be a prognostic factor for glioblastoma. This study aimed to investigate the anatomical location of tumor-related MGMT protein expression in histologically confirmed de novo glioblastoma multiforme (GBM). Preoperative magnetic resonance images were retrospectively examined from GBM patients. Tumor tissues were manually segmented based on the structural image of each patient and subsequently registered to a standard brain atlas. Superimposition of the tumor tissues was carried out in patients with and without epigenetic changes. We used voxel-based lesion symptom mapping (VLSM) to identify the specific brain regions that were associated with level of MGMT protein expression. The tumors with low expression of MGMT protein and those with high expression of MGMT protein showed not significant differences in tumor size on T2 imaging. The VLSM analysis demonstrated that tumors with low expression of MGMT protein were more likely to occur in the right temporal-parietal lobe, while tumors with high expression of MGMT protein occurred more often in the left frontal lobe. Based upon VLSM data, our results suggest that the epigenetic changes, which occur during tumorigenesis, may have anatomical specificity. The identified correlation between molecular biomarkers and anatomical distribution underscores the current understanding of the biological characteristics of glioblastoma.

Tumor border sharpness correlates with HLA-G expression in low-grade gliomas

Human leukocyte antigen-G (HLA-G) is a tumor microenvironment molecule that is involved in the escape of cancerous tumors from host immune recognition and destruction. This study investigated the potential relationship between HLA-G expression levels and the sharpness of low-grade glioma tumor borders in magnetic resonance images. Preoperative T2-weighted images from 72 patients were retrospectively examined by manually segmenting the hyperintensive tumor areas and subsequently registering them to a standard brain template. Then, the intensity of the voxels inside the tumor border (tumor voxels) was compared with that of the voxels outside the tumor border (paratumor voxels). The radiologic sharpness of a tumor was defined as the mean ratio of the intensity of the tumor voxels to the intensity of the paratumor voxels. Tumors with high HLA-G expression were associated with larger tumors and lower mean hyperintensive contrast. These findings suggest that tumors with blurred boundaries may be those prone to diffuse invasion. Additionally, patients with tumors having high HLA-G expression were less likely to have undergone complete resections. Thus, this study is the first to identify an association between HLA-G expression and the radiologic morphology of the tumor border, and may further our understanding of the role of the HLA gene in immune escape in patients with low-grade gliomas.

Mapping p53 Mutations in Low-Grade Glioma: A Voxel-Based Neuroimaging Analysis

Brain tumor location has prognostic implications so these authors explored whether location also correlated with p53 status in 182 patients. Tumors occurring in the left medial temporal and right anterior temporal lobes were associated with high expression of mutant p53 and had significantly worse progression-free survival. BACKGROUND AND PURPOSE: Brain tumor location has proved to be a prognostic factor that may be associated with features of neoplastic origin. Mutation of p53 is an atypical genetic change that occurs during tumorigenesis. Thus, a potential correlation may exist between tumor location and p53 status. The purpose of the current study was to identify anatomic characteristics of mutant p53 expression by using quantitative neuroimaging analyses. MATERIALS AND METHODS: Preoperative MR images from 182 patients with histologically confirmed low-grade gliomas were retrospectively analyzed. All tumors were manually marked and registered to the standard space. Using a voxel-based lesion-symptom mapping analysis, we located brain regions associated with a high occurrence of p53 mutation and corrected them by using a permutation test. The acquired clusters were further included as a factor in survival analyses. RESULTS: Statistical analysis demonstrated that the left medial temporal lobe and right anterior temporal lobe were specifically associated with high expression of mutant p53. Kaplan-Meier curves showed that tumors located in these regions were associated with significantly worse progression-free survival compared with tumors occurring elsewhere. CONCLUSIONS: Our voxel-level imaging analysis provides new evidence that genetic changes during cancer may have anatomic specificity. Additionally, the current study suggests that tumor location identified on structural MR images could potentially be used for customized presurgical outcome prediction.

Anatomical localization of p53 mutated tumors: A radiographic study of human glioblastomas

Accumulating evidence has suggested that tumor location is linked to the genetic profile of gliomas. Therefore, the aim of this study was to investigate the anatomical characteristics of p53-mutated glioblastomas. We also sought to provide new insight into the possible niche locations of cells of glioblastoma origin. In order to accomplish this, preoperative magnetic resonance images from 163 patients with primary glioblastomas were retrospectively analyzed. All tumors were manually marked and registered to the standard space. Using the voxel-based lesion-symptom mapping approach, voxels exhibiting the strongest correlations with p53 mutants were identified. T-values of voxels that were greater than 95% of the permutations were factored into the results of the mapping analysis. Distinct anatomical characteristics between p53-mutated and wild-type glioblastomas were demonstrated using this approach. More specifically, we found that p53-mutated glioblastomas were preferentially located in the frontal lobe in the area surrounding the rostral extension of the lateral ventricles. The distinct anatomical characteristics of p53-mutated and wild-type glioblastomas provide further evidence that these gliomas arise from distinct niche locations.

MRI features can predict EGFR expression in lower grade gliomas: A voxel-based radiomic analysis

AbstractObjectiveTo identify the magnetic resonance imaging (MRI) features associated with epidermal growth factor (EGFR) expression level in lower grade gliomas using radiomic analysis.Methods270 lower grade glioma patients with known EGFR expression status were randomly assigned into training (n=200) and validation (n=70) sets, and were subjected to feature extraction. Using a logistic regression model, a signature of MRI features was identified to be predictive of the EGFR expression level in lower grade gliomas in the training set, and the accuracy of prediction was assessed in the validation set.ResultsA signature of 41 MRI features achieved accuracies of 82.5% (area under the curve [AUC] = 0.90) in the training set and 90.0% (AUC = 0.95) in the validation set. This radiomic signature consisted of 25 first-order statistics or related wavelet features (including range, standard deviation, uniformity, variance), one shape and size-based feature (spherical disproportion), and 15 textural features or related wavelet features (including sum variance, sum entropy, run percentage).ConclusionsA radiomic signature allowing for the prediction of the EGFR expression level in patients with lower grade glioma was identified, suggesting that using tumour-derived radiological features for predicting genomic information is feasible.Key Points• EGFR expression status is an important biomarker for gliomas. • EGFR in lower grade gliomas could be predicted using radiogenomic analysis. • A logistic regression model is an efficient approach for analysing radiomic features.

Anatomical Involvement of the Subventricular Zone Predicts Poor Survival Outcome in Low-Grade Astrocytomas

The subventricular zone (SVZ) has been implicated in the origination, development, and biological behavior of gliomas. Tumor-SVZ contact is also postulated to be a poor prognostic factor in glioblastomas. We aimed to evaluate the prognostic consequence of the anatomical involvement of low-grade gliomas with the SVZ. To that end, we reviewed 143 patients with diffuse astrocytomas, and tumor lesions were manually delineated on magnetic resonance images. We initially investigated the prognostic role of SVZ contact in all patients. Additionally, we investigated the influence of the anatomical proximity of the tumor lesion centroids to the SVZ in the SVZ-involved patient cohorts, as well as location within the SVZ. We found SVZ contact with tumors to be a significant prognostic factor of overall survival in all patients with diffuse astrocytomas (p = 0.027). In the SVZ-involved cohort, a shorter distance from the tumor centroid to the SVZ (≤30 mm) correlated with shorter overall survival (p = 0.022) on univariate analysis. However, there was no significant difference in overall survival with respect to the SVZ region involved with the tumor (p = 0.930). Multivariate analysis showed that a shorter distance between the tumor centroid and the SVZ (p = 0.039) was significantly associated with poor overall survival in SVZ-involved patients. Hence, this study helps establish the prognostic role of the anatomical interaction of tumors with the SVZ in low-grade astrocytomas.

ADAM9 Expression Is Associate with Glioma Tumor Grade and Histological Type, and Acts as a Prognostic Factor in Lower-Grade Gliomas.

The A disintegrin and metalloproteinase 9 (ADAM9) protein has been suggested to promote carcinoma invasion and appears to be overexpressed in various human cancers. However, its role has rarely been investigated in gliomas and, thus, in the current study we have evaluated ADAM9 expression in gliomas and examined the relevance of its expression in the prognosis of glioma patients. Clinical characteristics, RNA sequence data, and the case follow-ups were reviewed for 303 patients who had histological, confirmed gliomas. The ADAM9 expression between lower-grade glioma (LGG) and glioblastoma (GBM) patients was compared and its association with progression-free survival (PFS) and overall survival (OS) was assessed to evaluate its prognostic value. Our data suggested that GBM patients had significantly higher expression of ADAM9 in comparison to LGG patients (p < 0.001, t-test). In addition, among the LGG patients, aggressive astrocytic tumors displayed significantly higher ADAM9 expression than oligodendroglial tumors (p < 0.001, t-test). Moreover, high ADAM9 expression also correlated with poor clinical outcome (p < 0.001 and p < 0.001, log-rank test, for PFS and OS, respectively) in LGG patients. Further, multivariate analysis suggested ADAM9 expression to be an independent marker of poor survival (p = 0.002 and p = 0.003, for PFS and OS, respectively). These results suggest that ADAM9 mRNA expression is associated with tumor grade and histological type in gliomas and can serve as an independent prognostic factor, specifically in LGG patients.

Age-associated brain regions in gliomas: a volumetric analysis.

Both age of patients and tumor location are associated with tumor origin, genetic characteristics, and prognosis. The objective of this study was to investigate the relationship between tumor location and age at diagnosis in a large cohort of patients with a primary diagnosis of glioma. We consecutively enrolled a cohort of 200 adults with glioblastoma and another cohort of 200 adults with diffuse low-grade gliomas. The magnetic resonance images of all tumors were manually segmented and then registered to a standard brain space. By using voxel-by-voxel regression analysis, specific brains regions associated with advanced age at tumor diagnosis were localized. In the low-grade gliomas cohort, the brain regions associated with advanced age at tumor diagnosis were mainly located in the right middle frontal region, while a region in the left temporal lobe, particularly at the subgranular zone, was associated with lower age at tumor diagnosis. In the glioblastoma cohort, the brain regions associated with advanced age at tumor diagnosis were mainly located in the temporal lobe, particularly at the posterior region of the subventricular zones. A region in the left inferior frontal region was associated with lower age at tumor diagnosis. Significant differences in the age of patients were found between tumors located in the identified regions and those located elsewhere in both cohorts. The current study demonstrated the correlation between tumor location and age at diagnosis, which implies differences in the origin of gliomas in young and older patients.