Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma

Lee, Yi‐Ying; Chao, Tung-Bo; Sheu, Ming‐Jen; Tian, Yufeng; Chen, Tzu‐Ju; Lee, Sung‐Wei; He, Hao; Chang, I‐Wei; Hsing, Chung-Hsi; Lin, Ching‐Yih; Li, Chien‐Feng

doi:10.7150/jca.15667

Cited by 21 publications

(18 citation statements)

References 47 publications

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“…GAD1 is a rate-limiting enzyme in the production of γ-aminobutyric acid (GABA) and found in the GABAergic neurons in the central nervous system. In contrast to previous findings that reported an elevated GAD1 expression in oral, nasopharyngeal, and gastric cancers [59,60], we detected a significant decrease in GAD1 expression in cervical cancer tissues. The impaired GAD1 expression may be related to the gene hypermethylation in some neoplastic tissues [61].…”

Section: Discussioncontrasting

confidence: 99%

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Abudula¹,

Rouzi²,

Xu³

et al. 2019

Bosn J of Basic Med Sci

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Aberrant metabolic regulation has been observed in human cancers, but the corresponding regulation in human papillomavirus (HPV) infection-associated cervical cancer is not well understood. Here, we explored potential biomarkers for the early prediction of cervical carcinoma based on the metabolic profile of uterine cervical tissue specimens that were positive for HPV16 infection. Fifty-two fresh cervical tissues were collected from women confirmed to have cervical squamous cell carcinoma (SCC; n = 21) or cervical intraepithelial neoplasia (CIN) stages II-III (n = 20). Eleven healthy women constituted the controls (negative controls [NCs]). Real-time polymerase chain reaction (PCR) was performed to detect HPV infection in the tissues. High-resolution magic angle spinning nuclear magnetic resonance was utilized for the analysis of the metabolic profile in the tissues. The expression of rate-limiting enzymes involved in key metabolic pathways was detected by reverse-transcription quantitative PCR. An independent immunohistochemical analysis was performed using 123 cases of paraffin-embedded cervical specimens. A profile of 17 small molecular metabolites that showed differential expression in HPV16-positive cervical SCC or CIN II-III compared with HPV-negative NC group was identified. According to the profile, the levels of α-and β-glucose decreased, those of lactate and low-density lipoproteins increased, and the expression of multiple amino acids was altered. Significantly increased transcript and protein levels of glycogen synthase kinase 3 beta (GSK3β) and glutamate decarboxylase 1 (GAD1) and decreased transcript and protein levels of pyruvate kinase muscle isozyme 2 (PKM2) and carnitine palmitoyltransferase 1A (CPT1A) were observed in the patient group (p < 0.05). HPV infection and cervical carcinogenesis drive metabolic modifications that might be associated with the aberrant regulation of enzymes related to metabolic pathways.

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Section: Discussioncontrasting

confidence: 99%

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Abudula¹,

Rouzi²,

Xu³

et al. 2019

Bosn J of Basic Med Sci

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“…Furthermore, high CMIP levels were associated with worse prognosis (recurrence-free and overall survival) in gastric and breast cancers [43,45] and were related with herceptin resistance in HER2-positive gastric cancer cells [46]. Similarly, the enzyme encoded by GAD1 gene, which catalyzes the conversion of L-glutamic acid to γ-aminobutyric acid, has been found overexpressed in several types of tumors, including lung adenocarcinoma [47], nasopharyngeal carcinoma [48], oral squamous cell carcinoma [49], prostate cancer [50], and brain metastasis [51], being also found upregulated in colon and HCC cells in vitro [52]. In parallel, high GAD1 levels were also shown to correlate with the pathological stage of patients with lung adenocarcinoma, positively correlating with metastasis and with worse recurrence-free survival [47].…”

Section: Discussionmentioning

confidence: 99%

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

Lapitz

Arbelaiz

O’Rourke³

et al. 2020

Cells

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Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. the etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk Cells 2020, 9, 721 2 of 33 factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcriptomic profile of serum and urine extracellular vesicles (EVs) from patients with CCA, PSC, ulcerative colitis (UC), and healthy individuals. Serum and urine EVs were isolated by serial ultracentrifugations and characterized by nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting. EVs transcriptome was determined by Illumina gene expression array [messenger RNAs (mRNA) and non-coding RNAs (ncRNAs)]. Differential RNA profiles were found in serum and urine EVs from patients with CCA compared to control groups (disease and healthy), showing high diagnostic capacity. the comparison of the mRNA profiles of serum or urine EVs from patients with CCA with the transcriptome of tumor tissues from two cohorts of patients, CCA cells in vitro, and CCA cells-derived EVs, identified 105 and 39 commonly-altered transcripts, respectively. Gene ontology analysis indicated that most commonly-altered mRNAs participate in carcinogenic steps. Overall, patients with CCA present specific RNA profiles in EVs mirroring the tumor, and constituting novel promising liquid biopsy biomarkers.

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“…Over expression of GAD1 has been found in several cancers (including oral cancer, colorectal carcinoma, breast cancer, lymphoma and gastric cancer) and it can influence the proliferation, metastasis and chemoresistance of cancer cells [18][19][20]. Increasing research suggests that GAD1 has the potential to be a biomarker for prognosis prediction [21][22][23][24]. Tsuboi et al found that upregulation of GAD1 in lung adenocarcinoma patients showed significantly poorer prognosis for overall survival [22].…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Gene Signature Associated with Tumor Microenvironment of Cholangiocarcinoma

Chen¹,

Chen²,

Lu³

et al. 2021

Preprint

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Background: Cholangiocarcinoma (CCA) is the most common malignancy of the biliary tract with a dismal prognosis. Increasing evidence suggests that tumor microenvironment (TME) is closely associated with cancer prognosis. However, the prognostic signature for CCA based on TME has not yet been reported. This study aimed to develop a TME-related prognostic signature for accurately predicting the prognosis of patients with CCA. Methods: Based on the TCGA database, we calculated the stromal and immune scores using the ESTIMATE algorithm to assess TME in stromal and immune cells derived from CCA. TME-related differentially expressed genes were identified, followed by functional enrichment analysis and PPI network analysis. Univariate Cox regression analysis, Lasso Cox regression model and multivariable Cox regression analysis were performed to identify and construct the TME-related prognostic gene signature. Gene Set Enrichment Analyses (GSEA) was performed to further investigate the potential molecular mechanisms. The correlations between the risk scores and tumor infiltration immune cells were analyzed using Tumor Immune Estimation Resource (TIMER) database. Results: A total of 784 TME-related differentially expressed genes (DEGs) were identified, which were mainly enriched in immune-related processes and pathways. Among these TME-related DEGs, A novel two‑gene signature (including GAD1 and KLRB1) was constructed for CCA prognosis prediction. The AUC of the prognostic model for predicting the survival of patients at 1-, 2-, and 3- years was 0.811, 0.772, and 0.844, respectively. Cox regression analysis showed that the two‑gene signature was an independent prognostic factor. Based on the risk scores of the prognostic model, CCA patients were divided into high- and low-risk groups, and patients with high-risk score had shorter survival time than those with low-risk score. Furthermore, we found that the risk scores were negatively correlated with TME-scores and the number of several tumor infiltration immune cells, including B cells and CD4+ T cells. Conclusion: Our study established a novel TME-related gene signature to predict the prognosis of patients with CCA. This might provide a new understanding of the potential relationship between TME and CCA prognosis, and serve as a prognosis stratification tool for guiding personalized treatment of CCA patients.

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Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma

Cited by 21 publications

References 47 publications

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

Identification of Prognostic Gene Signature Associated with Tumor Microenvironment of Cholangiocarcinoma

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