Beta-Catenin and Gli-1 as prognostic markers in Glioblastoma Multiforme.
Marco RossiL MangoniPaolo TiniEmiliano MoriP TosiG OliveriElena CosciLuigi PirtoliClelia MiraccoAnnette Bakker
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Abstract BACKGROUND Despite our deeper understanding of the genomic alterations associated with glioblastoma (GBM), only a few genetic and epigenetic modifications have been proven to be meaningful in clinical practice. We have identified molecular parameters of prognostic relevance in IDHwt GBM using patient data from the Ohio State University (OSU) and the publicly available MSK-IMPACT database. METHODS A clinically annotated database of glioma patients at OSU- whose tumors were analyzed through Foundation One genomic testing- was utilized to examine mutation and copy number variation (CNV) data. 73 patients with IDHwt GBM were included in this study cohort along with 200 similar patients from the MSK-IMPACT cohort. Data from the MSKCC group was extracted from the cBioPortal database. Altered genes were correlated with clinical outcomes using Cox proportional hazards models. Univariate and multivariate analyses were applied, and variables included: MDM/P53, CDKN2A/B, CDK/CCND, RB1, EGFR/ ERBB, FGFR, PDGFR/KIT, NF1, PI3K, PI3K class 2, MYC and TERT promoter mutations. RESULTS Using univariate and multivariate analyses, EGFR activating alterations (amplification, mutations) and RB1 alterations (deletion, mutations) showed significant correlation with favorable outcome in IDHwt GBM: HR 0.496 for EGFR (p< 0.0001) and 0.454 for RB1 (p=0.025). Furthermore, the presence of PDGFR alterations, in EGFR altered tumors only, carried a significantly worse survival in univariate and multivariate analyses: HR 5.094 (p=0.004). This suggests an interaction between EGFR and PDGFR that could be of therapeutic relevance. CONCLUSIONS We found that GBM tumors harboring EGFR and/or RB1 alterations have better survival compared to tumors that are EGFR/RB1 wild-type. Moreover, PDGFR alterations worsens survival in EGFR altered GBM. This data provides further insights that might guide targeted therapies in IDHwt GBM.
CDKN2B
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The present study was planned to study the expression of C-myc and β-catenin in triple negative breast cancer (TNBC) tissue. Furthermore, their relations to clinical features of the tumor and the survival prognosis were also studied. Additionally, correlation was evaluated between the expression of C-myc and β-catenin to provide the theoretical basis for the targeted therapy of TNBC.Sixty cases of patients diagnosed with TNBC for the first time were selected for the study. The immumo-histochemical staining was employed to detect the positive expression rates of C-myc and β-catenin in cancer tissues and normal mammary tissues 3 cm away from the carcinoma. Fluorescence in situ hybridization (FISH) was used to test the gene amplification of C-myc in order to analyze the relation between C-myc and the protein expression of β-catenin. Further, kept the median follow-up time to 25.0 months in order to compare the survival prognosis.The positive expression rates of C-myc and β-catenin in cancer tissues were significantly higher than those in precancerous normal tissues (P<0.05). Furthermore, the expression rates were related with the diameter of tumor, clinical staging, pathological grading and lymphatic metastasis (P<0.5). There were 33 cases that exhibited an increase in C-myc gene copy number and the gene amplification was observed to be 55% in total. On the other hand, patients with positive expression of C-myc and β-catenin protein exhibited a shortened disease-free survival without tumor with an increasing recurrence rate and lower survival rate (P<0.05).The present study concludes that the positive expression of C-myc and β-catenin in TNBC tissue might be closely correlated with clinical features of cancer and the survival prognosis.
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Corrigendum on: Deng L, Liang H and Han Y (2020) Cyclooxygenase-2 and β-Catenin as Potential Diagnostic and Prognostic Markers in Endometrial Cancer. Front. Oncol. 10:56. doi:10.3389/fonc.2020.00056.In the original article, there was a mistake in the supplementary table named Table S3 AUCs, Sensitivity, Specificity of cox2, β-catenin and wnt3a in predicting diagnosis, myometrial invasion, vessel invasion, lymph node metastasis, and poor prognosis as published. The specificity of wnt3a in serum for myometrial invasion is 0.316 and the p value is 0.010. The corrected Table S3 AUCs, Sensitivity, Specificity of cox2, β-catenin and wnt3a in predicting diagnosis, myometrial invasion, vessel invasion, lymph node metastasis, and poor prognosis appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.An author was incorrectly labeled as Haiyan Liang 1 ,as she is the co-correspondence author, the correct label is Haiyan Liang 1* . The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
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