scholarly journals FXYD2 mRNA Expression Represents a New Independent Factor That Affects Survival of Glioma Patients and Predicts Chemosensitivity of Patients to Temozolomide

Author(s):  
Fang Wang ◽  
Kaijia Zhou ◽  
Tao Jiang ◽  
Hui Liang ◽  
Ming Zhang

Abstract Glioma is the most common primary intracranial tumor. Owing to the poor prognosis associated with high-grade gliomas, there is an urgent need to identify biomarkers related to prognosis and treatment sensitivity. Clinical features, FXYD2 mRNA expression levels, and survival data were analyzed for 1265 glioma samples from the Chinese Glioma Genome Map Project and two independent databases. The expression patterns for FXYD2 mRNA were compared using the chi-square test, and overall survival (OS) of glioma patients was evaluated according to FXYD2 mRNA expression levels. The factors affecting glioma survival were evaluated by Cox univariate and multivariate regression analysis. We found patients with primary oligodendroglioma, low World Health Organization (WHO) grade, low WHO molecular grade, isocitrate dehydrogenase (IDH) mutation, and combined deletion of 1p19q showed higher FXYD2 mRNA expression and longer survival times. Moreover, temozolomide (TMZ) chemotherapy was found to be an independent factor affecting survival in patients with high FXYD2 mRNA expression, but not in patients with low expression. So FXYD2 mRNA expression represents a new independent factor affecting the survival of glioma patients and may serve as an independent prognostic indicator to predict the sensitivity of gliomas to TMZ.

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kaijia Zhou ◽  
Tao Jiang ◽  
Yanwei Liu ◽  
Zheng Zhao ◽  
Lijie Huang ◽  
...  

Abstract Purpose Glioma is the most common primary intracranial tumor. Owing to the poor prognosis associated with high-grade gliomas, there is an urgent need to identify biomarkers related to prognosis and treatment sensitivity. Here, we analyze the expression of FXYD2 mRNA in gliomas, and explore its clinical prognostic value and significance in this disease. Methods Clinical features, FXYD2 mRNA expression levels, and survival data were analyzed for 516 glioma patients from the Chinese Glioma Genome Map Project, 481 from the cancer genome map datbase and 268 from the molecular braintumor database. The expression patterns for FXYD2 mRNA were compared using the chi-square test, and overall survival (OS) of glioma patients was evaluated according to FXYD2 mRNA expression levels. The factors affecting glioma survival were evaluated by Cox univariate and multivariate regression analysis. Results FXYD2 mRNA expression was related to the grade of gliomas. The higher the level, the lower the expression. Meanwhile related to the pathological classification of gliomas. Oligodendroglioma, IDH-mutant and 1p/19q-codeleted was higher than Astrocytoma, IDH-mutant, higher than Glioblastoma, IDH-wildtype. Moreover, temozolomide (TMZ) chemotherapy was found to be an independent factor affecting survival in patients with high FXYD2 mRNA expression, but not in patients with low expression. Conclusion FXYD2 mRNA expression represents a new independent factor affecting the survival of glioma patients and may serve as an independent prognostic indicator to predict the sensitivity of gliomas to TMZ.


2020 ◽  
Author(s):  
Yuting Ma ◽  
Junfeng Shi ◽  
Yongping Liu ◽  
Ruiyan Pan ◽  
Hongyan Qiu ◽  
...  

Abstract Background: Thyroid cancer (THCA) is a common head and neck malignancy. The family with sequence similarity 3 (FAM3) is a cytokine-like gene family with four members, which is presumed to participate in the development of many cancer types. However, the expression patterns of FAM3s in THCA and their prognostic values, have not yet been established. Methods: We investigated differential expressions of FAM3 mRNA and protein in THCA, then validated the findings for FAM3B by immunohistochemistry. We also investigated survival data with respect to FAM3 expression patterns in patients with THCA. FAM3s information regarding their relationships with clinical pathological parameters were obtained and FAM3 mutations were assessed. KEGG and GO pathway regarding FAM3C were obtained using online databases. To investigate potential correlations between FAM3s and immune cell infiltration, we investigated the roles of FAM3s in immune cells of patients with THCA. Results: The mRNA expression of FAM3C were significantly elevated in THCA tissues; high expression levels of FAM3C protein were also observed in THCA tissues. A significant association between the pathological stage and the expression of FAM3C was found in patients with THCA. Patients with THCA who had high mRNA expression levels of FAM3C exhibited significantly more favourable prognosis, compared with patients who had low mRNA expression levels of FAM3C. Conclusions: Overall, FAM3C may play vital roles in the pathogenesis and development of THCA, and these findings constitute novel insights for biomarkers of immunotherapeutic targeted agents and may aid in the identification of prognostic biomarkers for THCA.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Weiwei Gong ◽  
Yueyang Liu ◽  
Eleftherios P. Diamandis ◽  
Marion Kiechle ◽  
Holger Bronger ◽  
...  

Abstract Background High-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian cancer. A growing body of evidence suggests tumor-supporting roles of several members of the kallikrein-related peptidase (KLK) family, including KLK5 and KLK7, in this cancer subtype. In normal physiology, KLK5 and KLK7 are the major proteases involved in skin desquamation. Moreover, in several cancer types KLK5 and KLK7 co-expression has been observed. Recently, we have shown that elevated KLK5 mRNA levels are associated with an unfavorable prognosis in HGSOC. Therefore, the aim of this study was to investigate the clinical significance of KLK7 mRNA expression and to explore its relation to KLK5 levels in HGSOC. Methods mRNA expression levels of KLK7 were quantified by qPCR in a well-characterized patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO III/IV, n = 139). Previously determined KLK5 mRNA as well as KLK5 and KLK7 antigen concentrations were used to evaluate the relationship between the expression patterns of both factors on the mRNA as well as protein level in tumor tissue of HGSOC patients. Results There were strong, significant positive correlations between KLK5 and KLK7 both at the mRNA and the protein level, suggesting coordinate expression of these proteases in HGSOC. In univariate analyses, elevated KLK7 levels as well as the combination of KLK5 + KLK7 (high and/or high versus low/low) were significantly associated with worse progression-free survival (PFS). High mRNA expression levels of KLK7 and the combination of KLK5 and KLK7 showed a trend towards significance for overall survival (OS). In multivariate analyses, KLK7 mRNA expression represented an unfavorable, statistically significant independent predictor for PFS and OS. Conclusions The findings imply that both increased KLK5 and KLK7 mRNA expression levels represent unfavorable prognostic biomarkers in advanced high-grade serous ovarian cancer, whereby multivariate analyses indicate that KLK7 mRNA exhibits a stronger predictive value as compared to KLK5 mRNA and the combination of KLK5 and KLK7.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 383-383
Author(s):  
Martin K. H. Maus ◽  
Craig Stephens ◽  
Stephanie H. Astrow ◽  
Peter Philipp Grimminger ◽  
Dongyun Yang ◽  
...  

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.


2021 ◽  
Author(s):  
Chuan-hong Li ◽  
Lei Meng ◽  
Zhang-ming Chen ◽  
Wan-nian Sui ◽  
Pei-feng Chen ◽  
...  

Abstract Background:Members of the integrin β superfamily(ITGBs) have been shown to be aberrantly expressed in various human cancers and involved in tumorigenesis and progression. However, the diverse expression patterns and prognostic values of the entire ITGB family members in gastric cancer(GC) has not been systematically investigated.Methods:In the current study, Oncomine, GEPIA, Kaplan Meier plotter, TIMER, GeneMANIA, STRING and Metascape database were employed to explore the transcriptional and survival data of ITGB superfamily members in GC. Moreover, we confirmed the mRNA expression levels of ITGB superfamily members in GC cell lines by qRT-PCR.Results:The mRNA expression level of ITGB1/2/4/5/8 was upregulated in GC, while the expression level of ITGB7 was downregulated. Higher expression of ITGB2/7 was significantly associated with the tumor stage of patients with GC. However, we found that the expression level of ITGB1/2/4/5/6/7/8 was remarkably increased in GC cell lines compared to stomach normal cell lines, while ITGB3 expression was decreased in the former than in the latter. Meanwhile,higher expression levels of ITGB2/6/7 were closely correlated with better overall clinical survival (OS) and recurrence-free survival (RFS) in GC patients, while higher ITGB3/4/5 expression were strongly associated with poorer OS and RFS.We also discovered that the functions of ITGBs and their adjacent genes are mainly related to protein complexes involved in cell adhesion. the functions of ITGBs and their adjacent proteins are mainly related to focal adhesion, cell adhesion molecules, proteoglycans in cancer, small cell lung cancer, rap1 signaling pathway, IgA production by intestinal immune network, and microRNAs in cancer.In addition, the expression of ITGBs was significantly correlated with the infiltration of multiple immune cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells.Conclusions:Our results suggested that abnormal expression of ITGBs plays a key role in the progression of GC and that ITGBs may be potential prognostic biomarkers and therapeutic targets for GC.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bin Xu ◽  
Zhengyuan Huo ◽  
Hui Huang ◽  
Wei Ji ◽  
Zheng Bian ◽  
...  

Abstract Background The epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of the tyrosine kinase I subfamily and has 4 members: EGFR/ERBB1, ERBB2, ERBB3, and ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers. Materials/methods In this study, we used multiple online bioinformatics websites, including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID, to study the expression profiles, prognostic values and immune infiltration correlations of the EGFR family in glioma. Results We found that EGFR and ERBB2 mRNA expression levels were higher in glioblastoma (GBM, WHO IV) than in other grades (WHO grade II & III), while the ERBB3 and ERBB4 mRNA expression levels were the opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were upregulated, which was associated with a poor prognosis. In addition, correlation analysis between EGFR family expression levels and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. The PPI network of the EGFR family in glioma and enrichment analysis showed that the EGFR family and its interactors mainly participated in the regulation of cell motility, involving integrin receptors and Rho family GTPases. Conclusions In summary, the results of this study indicate that the EGFR family members may become potential therapeutic targets and new prognostic markers for glioma.


2021 ◽  
Author(s):  
Santiago Manuel Gomez Bergna ◽  
Abril Marchesini ◽  
Leslie Cinthya Amoros Morales ◽  
Paula Nazarena Arrias ◽  
Hernan Gabriel Farina ◽  
...  

Breast cancer is the most common cancer as well as the first cause of death by cancer in women worldwide. BIRC6 (baculoviral IAP repeat-containing protein 6) is a member of the inhibitors of apoptosis protein family thought to play an important role in the progression or chemoresistance of many cancers. The aim of the present work was to investigate the role of apoptosis inhibitor BIRC6 in breast cancer, focusing particularly on its involvement in the metastatic cascade. We analyzed BIRC6 mRNA expression levels and Copy Number Variations (CNV) in three breast cancer databases from The Cancer Genome Atlas (TCGA) comparing clinical and molecular attributes. Genomic analysis was performed using CBioportal platform while transcriptomic studies (mRNA expression levels, correlation heatmaps, survival plots and Gene Ontology) were performed with USC Xena and R. Statistical significance was set at p values less than 0.05. Our analyses showed that there was a differential expression of BIRC6 in cancer samples when compared to normal samples. CNV that involve amplification and gain of BIRC6 gene were correlated with negative hormone receptor tumors, higher prognostic indexes, younger age at diagnosis and both chemotherapy and radiotherapy administration. Transcriptomic and gene-ontology analyses showed that, in conditions of high BIRC6 mRNA levels, there are differential expression patterns in apoptotic, proliferation, and metastatic pathways. In summary, our in silico analyses suggest that BIRC6 exhibits an antiapoptotic, pro-proliferative and an apparent pro-metastatic role and could be a relevant molecular target for treatment of Breast Cancer tumors.


2021 ◽  
Author(s):  
bin xu ◽  
wei ji ◽  
zhengyuan huo ◽  
zheng bian ◽  
jiantong jiao ◽  
...  

Abstract Background: Epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of tyrosine kinase I subfamily, including 4 members, they are EGFR/ERBB1, ERBB2, ERBB3, ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers.Material/Methods: In this research, we used multiple online bioinformatics websites including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID to study the expression profiles, prognostic values and immune infiltration correlations of EGFR family in glioma.Results: We found that EGFR and ERBB2 mRNA expression levels were the higher in glioblastoma (GBM, WHO IV) than other grades (WHO grade II&III), While ERBB3 and ERBB4 mRNA expression levels were opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were the opposite. Besides, ERBB2 and ERBB4 in glioma patients were associated with poor prognosis. In addition, correlation analysis between EGFR family expression and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. PPI network of EGFR family in glioma and enrichment analysis showed that EGFR family and their interactors mainly participated in regulation of cell motility involved integrin receptors and Rho family GTPases.Conclusions: In summary, this study indicates that EGFR family may become potential targets and new prognostic markers for glioma.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Meng-Lu Zeng ◽  
Xian-Jin Zhu ◽  
Jin Liu ◽  
Peng-Chong Shi ◽  
Yan-Li Kang ◽  
...  

Background. S100 family genes exclusively encode at least 20 calcium-binding proteins, which possess a wide spectrum of intracellular and extracellular functions in vertebrates. Multiple lines of evidences suggest that dysregulated S100 proteins are associated with human malignancies including colorectal cancer (CRC). However, the diverse expression patterns and prognostic roles of distinct S100 genes in CRC have not been fully elucidated. Methods. In the current study, we analyzed the mRNA expression levels of S100 family genes and proteins and their associations with the survival of CRC patients using the Oncomine analysis and GEPIA databases. Expressions and mutations of S100 family genes were analyzed using the cBioPortal, and protein-protein interaction (PPI) networks of S100 proteins and their mutation-related coexpressed genes were analyzed using STRING and Cytoscape. Results. We observed that the mRNA expression levels of S100A2, S100A3, S100A9, S100A11, and S100P were higher and the level of S100B was lower in CRC tissues than those in normal colon mucosa. A high S100A10 levels was associated with advanced-stage CRC. Results from GEPIA database showed that highly expressed S100A1 was correlated with worse overall survival (OS) and disease-free survival (DFS) and that overexpressions of S100A2 and S100A11 were associated with poor DFS of CRC, indicating that S100A1, S100A2, and S100A11 are potential prognostic markers. Unexpectedly, most of S100 family genes showed no significant prognostic values in CRC. Conclusions. Our findings, though still need to be ascertained, offer novel insights into the prognostic implications of the S100 family in CRC and will inspire more clinical trials to explore potential S100-targeted inhibitors for the treatment of CRC.


Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2043
Author(s):  
Mario Mischkulnig ◽  
Barbara Kiesel ◽  
Daniela Lötsch ◽  
Thomas Roetzer ◽  
Martin Borkovec ◽  
...  

5-Aminolevulinic acid (5-ALA) is a fluorescent dye that after metabolization to Protoporphyrin IX (PpIX) by the heme biosynthesis pathway typically leads to visible fluorescence in WHO grade IV but not grade II gliomas. The exact mechanism for high PpIX levels in WHO grade IV gliomas and low PpIX levels in WHO grade II gliomas is not fully clarified. To detect relevant changes in mRNA expression, we performed an in-silico analysis of WHO grade II and IV glioma sequencing datasets provided by The Cancer Genome Atlas (TCGA) to investigate mRNA expression levels of relevant heme biosynthesis genes: Solute Carrier Family 15 Member 1 and 2 (SLC15A1 and SLC15A2), Aminolevulinate-Dehydratase (ALAD), Hydroxymethylbilane-Synthase (HMBS), Uroporphyrinogen-III-Synthase (UROS), Uroporphyrinogen-Decarboxylase (UROD), Coproporphyrinogen-Oxidase (CPOX), Protoporphyrinogen-Oxidase (PPOX), ATP-binding Cassette Subfamily B Member 6 (ABCB6)/G Member 2 (ABCG2) and Ferrochelatase (FECH). Altogether, 258 WHO grade II and 166 WHO grade IV samples were investigated. The mRNA expression levels showed significant differences in 8 of 11 examined genes between WHO grade II and IV gliomas. Significant differences in mRNA expression included increases of HMBS, UROD, FECH and PPOX as well as decreases of SLC15A2, ALAD, UROS and ABCB6 in WHO IV gliomas. Since the majority of changes was found in directions that might actually impair PpIX accumulation in WHO grade IV gliomas, additional studies are needed to analyze the corresponding factors of the heme biosynthesis also on protein level.


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