scholarly journals Elevating PKM2 Expression Indicates a Biomarker of Poor Prognosis in Patients With Liver Cancer

2021 ◽  
Author(s):  
Chaoxiang Lv ◽  
Qiqi Zhang ◽  
Yuanguo Li ◽  
Entao Li ◽  
Fangxu Li ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Poor Prognosis ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Predictive Biomarker ◽  
Normal Tissues ◽  
Diagnosis And Prognosis ◽  
Cox Analysis ◽  
T Classification

Abstract M2 isoform of pyruvate kinase (PKM2) plays an important role in reprogramming of cell metabolism which is a hall-marker of tumorigenesis. PKM2 expression altering is closely related to cancer metabolism and tumor growth. In the present study, we analyzed the role of PKM2 expression in liver cancer in order to clarify its potential application value in the diagnosis and prognosis of liver cancer patients. In cancerous liver tissues, the PKM2 expression was significantly higher than normal tissues. High PKM2 expressing was related to patient’s age, gender, histological type, grade, stage, T classification and poor survival. Patients with Higher PKM2 expression had a shorter OS (P = 0.0013) and RFS (P = 0.027). ROC and Multivariate Cox analysis showed that high PKM2expression was a risk factor for patients’ poor prognosis. GSEA identified mitotic spindle, PI3K/Akt/mTOR signaling, notch signaling, apoptosis, G2M checkpoint and Wnt/β- Cantenin signaling were enriched with high PKM2 expression phenotype. These findings suggested PKM2 expression has potential as a predictive biomarker for the diagnosis and prognosis of patients with liver cancer.

scholarly journals Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001364
Author(s):  
Yan Zhang ◽  
Hui Yang ◽  
Jun Zhao ◽  
Ping Wan ◽  
Ye Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Metabolism ◽  
Vital Role ◽  
Methionine Metabolism ◽  
Promoter Regions ◽  
Normal Tissues ◽  
Methionine Cycle

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.

scholarly journals Peroxisome Metabolism in Cancer

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1692 ◽  
Author(s):  
Jung-Ae Kim
Keyword(s):  
Metabolic Pathways ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Critical Role ◽  
Acid Oxidation ◽  
Metabolic Dysregulation ◽  
Human Disorders ◽  
Peroxisomal Function ◽  
Target Cancer

Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redoxbalance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acidsynthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations inperoxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linkedto metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-relateddisorders, revealing the significance of peroxisome metabolism in human health. Cancer is a diseasewith metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functionaleects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles,such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated thanit is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomesand the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential ofinactivating peroxisomes to target cancer metabolism, which may pave the way for more eectivecancer treatment.

scholarly journals A Novel TGF-β Risk Score Predicts the Clinical Outcomes and Tumour Microenvironment Phenotypes in Bladder Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhi Liu ◽  
Tiezheng Qi ◽  
Xiaowen Li ◽  
Yiyan Yao ◽  
Belaydi Othmane ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Risk Score ◽  
Tumour Microenvironment ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Immune Checkpoints ◽  
Normal Tissues ◽  
Cox Analysis

BackgroundThe TGF-β pathway plays critical roles in numerous malignancies. Nevertheless, its potential role in prognosis prediction and regulating tumour microenvironment (TME) characteristics require further elucidation in bladder cancer (BLCA).MethodsTGF-β-related genes were comprehensively summarized from several databases. The TCGA-BLCA cohort (training cohort) was downloaded from the Cancer Genome Atlas, and the independent validation cohorts were gathered from Xiangya Hospital (Xinagya cohort) and Gene Expression Omnibus. Initially, we identified differentially expressed TGF-β genes (DEGs) between cancer and normal tissues. Subsequently, univariate Cox analysis was applied to identify prognostic DEGs, which were further used to develop the TGF-β risk score by performing LASSO and multivariate Cox analyses. Then, we studied the role of the TGF-β risk score in predicting prognosis and the TME phenotypes. In addition, the role of the TGF-β risk score in guiding precision treatments for BLCA has also been assessed.ResultsWe successfully constructed a TGF-β risk score with an independent prognostic prediction value. A high TGF-β risk score indicated an inflamed TME, which was supported by the positive relationships between the risk score, enrichment scores of anticancer immunity steps, and the infiltration levels of tumour-infiltrating immune cells. In addition, the risk score positively correlated with the expression of several immune checkpoints and the T cell inflamed score. Consistently, the risk score was positively related to the enrichment scores of most immunotherapy-positive pathways. In addition, the sensitivities of six common chemotherapeutic drugs were positively associated with the risk score. Furthermore, higher risk score indicated higher sensitivity to radiotherapy and EGFR-targeted therapy. On the contrary, patients with low-risk scores were more sensitive to targeted therapies, including the blockade of FGFR3 and WNT-β-catenin networks.ConclusionsWe first constructed and validated a TGF-β signature that could predict the prognosis and TME phenotypes for BLCA. More importantly, the TGF-β risk score could aid in individual precision treatment for BLCA.

scholarly journals The role of the oral microbiome in the diagnosis and prognosis of tumors of the oral cavity

2021 ◽  
Vol 70 (2) ◽  
Author(s):  
Aurelia Spinei ◽  
◽  
Anca Chiriac ◽  
Iurie Spinei ◽  
Gheorghe Tibirna ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Prognostic Biomarker ◽  
Host Immunity ◽  
Oral Microbiome ◽  
Therapeutic Approaches ◽  
Diagnosis And Prognosis ◽  
Recent Advancement ◽  
Oral Tumors ◽  
Virulence Properties

Despite advancement in tumors treatment, oral cancer has a poor prognosis and is often detected at late stage. Recent advancement in metagenomic technologies may be useful in identifying oral tumors–related microbiome, their genomes, virulence properties, and their interaction with host immunity. Alteration in the oral commensal microbial communities have potential application as a diagnostic tool to predict oral tumors. To develop highly precise and effective therapeutic approaches, identification of specific oral microbiomes may be required. In this review, we narrate the role of microbiome in the progression of oral tumors and its role as an early diagnostic and prognostic biomarker for oral tumors.

scholarly journals Non-Genomic Control of Dynamic MYCN Gene Expression in Liver Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Xian-Yang Qin ◽  
Luc Gailhouste
Keyword(s):  
Gene Expression ◽  
Liver Cancer ◽  
Dna Amplification ◽  
Predictive Biomarker ◽  
Cellular Level ◽  
Diagnostic Strategies ◽  
Lipid Desaturation ◽  
Tumor Suppressive Mirnas ◽  
Post Transcriptional Regulation

Upregulated MYCN gene expression is restricted to specialized cell populations such as EpCAM+ cancer stem cells in liver cancer, regardless of DNA amplification and mutation. Here, we reviewed the role of MYCN gene expression in liver homeostasis, regeneration, and tumorigenesis, and discussed the potential non-genomic mechanisms involved in controlling MYCN gene expression in liver cancer, with a focus on inflammation-mediated signal transduction and microRNA-associated post-transcriptional regulation. We concluded that dynamic MYCN gene expression is an integrated consequence of multiple signals in the tumor microenvironment, including tumor growth-promoting signals, lipid desaturation-mediated endoplasmic reticulum stress adaptation signals, and tumor suppressive miRNAs, making it a potential predictive biomarker of tumor stemness and plasticity. Therefore, understanding and tracing the dynamic changes and functions of MYCN gene expression will shed light on the origin of liver tumorigenesis at the cellular level and the development of novel therapeutic and diagnostic strategies for liver cancer treatment.

scholarly journals TMEM88 is a Prognostic Biomarker and Correlates With Immune Infiltrates in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Andrew Liman ◽  
Yang Gu ◽  
Pengpeng Liu ◽  
Quanyan Liu
Keyword(s):  
Liver Cancer ◽  
Cancer Progression ◽  
Prognostic Biomarker ◽  
Progression Free Survival ◽  
Free Survival ◽  
Multiple Tumor ◽  
Normal Tissues ◽  
Tumor Types ◽  
Disease Stages

Abstract BackgroundTransmembrane protein 88 (TMEM88) has emerged as a newly discovered cancer-related protein that acts as a cancer-promoting or cancer-inhibiting regulator in multiple tumor types. However, the exact role of TMEM88 in liver cancer is undetermined. The current study was designed to determine the expression of TMEM88 in liver cancer. ResultsTMEM88 expression was significantly lower in several human cancers, but higher in liver and bile cancer, than in corresponding normal tissues. TMEM88 expression in HCC tissues correlated with prognosis. Low TMEM88 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at late disease stages (grade 2 and 3). TMEM88 showed strong correlation with tumor-infiltrating B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. ConclusionThese findings demonstrate that TMEM88 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.

scholarly journals WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?

2014 ◽  
Vol 35 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Victoria Sherwood
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Critical Role ◽  
Oncogenic Signaling ◽  
Cancer Cell Metabolism ◽  
Oncogenic Signaling Pathways

WNT signaling was discovered in tumor models and has been recognized as a regulator of cancer development and progression for over 3 decades. Recent work has highlighted a critical role for WNT signaling in the metabolic homeostasis of mammals, where its misregulation has been heavily implicated in diabetes. While the majority of WNT metabolism research has focused on nontransformed tissues, the role of WNT in cancer metabolism remains underinvestigated. Cancer is also a metabolic disease where oncogenic signaling pathways regulate energy production and macromolecular synthesis to fuel rapidly proliferating tumors. This review highlights the emerging evidence for WNT signaling in the reprogramming of cancer cell metabolism and examines the role of these signaling pathways as mediators of tumor bioenergetics.

scholarly journals High TRIM44 expression as a valuable biomarker for diagnosis and prognosis in cervical cancer

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Shuang Liu ◽  
Fanling Meng ◽  
Jing Ding ◽  
Hongying Ji ◽  
Mu Lin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Clinical Significance ◽  
Poor Prognosis ◽  
Malignant Tumors ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Normal Tissues ◽  
Diagnosis And Prognosis ◽  
Gynecology And Obstetrics

Abstract Tripartite motif containing 44 (TRIM44) has been reported to be up-regulated in multiple aggressive malignant tumors. However, its expression status and clinical significance in cervical cancer remain unknown. The purpose of this study was to investigate the clinical significance of TRIM44 expression and the prognosis in patients with cervical cancer (CC). Fresh frozen tissues from 5 samples of CC and 4 normal cervical tissues were analyzed for TRIM44 expression using RT- PCR and Western blot analysis. 122 paraffin-embedded surgical specimens from patients with CC were collected for an immunohistochemistry. TRIM44 expression was found to be significantly up-regulated in cervical cancer specimens compared with adjacent normal tissues (P<0.001). Statistical analysis showed that TRIM44 expression was significantly correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and lymph node metastasis, but not with age, histological type, and tumor size. Kaplan–Meier survival analysis suggested that high TRIM44 expression was associated with poor prognosis. Patients highly expressing TRIM44 have significantly shorter overall survival (OS) (P=0.006) and disease-free survival (DFS) (P=0.002). Furthermore, multivariate Cox analysis showed TRIM44 was an independent risk factor for poor prognosis. Our study demonstrated that TRIM44 expression contributes to the progression of cervical cancer, and could be used as a marker of clinical diagnosis and prognosis of patients with cervical cancer.

scholarly journals Overexpression of P4HA1 Is Correlated with Poor Survival and Immune Infiltrates in Lung Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Haiting Zhou ◽  
Yi He ◽  
Lingling Li ◽  
Cheng Wu ◽  
Guoqing Hu
Keyword(s):  
Lung Adenocarcinoma ◽  
Clinical Decision ◽  
Bioinformatic Analysis ◽  
Normal Tissues ◽  
Pathological Type ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Cox Analysis ◽  
T Classification ◽  
The Relationship

Lung adenocarcinoma (LUAD) is a major pathological type of lung cancer. Understanding the mechanism of LUAD at the molecular level is important for a clinical decision. In this study, we use bioinformatic analysis to explore the prognostic value of P4HA1 in lung adenocarcinoma (LUAD) and the relationship with prognosis and tumor-infiltrating immune cells (TIICs). The results showed that the expression of P4HA1 was significantly higher in tumor tissues than in normal tissues for LUAD patients. Upregulated P4HA1 was related to stage and T classification. Kaplan-Meier analysis indicated that upregulation of P4HA1 was significantly related to worse overall survival (OS). Univariate and multivariate Cox analysis indicated P4HA1 remained to be an independent prognostic factor. GSEA showed that several cancer-related and immune-related signaling pathways exhibited prominently differential enrichment in P4HA1-high expression phenotype. In addition, the expression of P4HA1 was significantly correlated with proportion of several TIICs, particularly B cells and CD4+ T cells. In conclusion, our study confirmed that P4HA1 is a promising biomarker of poor prognosis and relates to immune infiltrates in LUAD.

scholarly journals Role of Mitochondria in Cancer Stem Cell Resistance

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1693 ◽  
Author(s):  
José Manuel García-Heredia ◽  
Amancio Carnero
Keyword(s):  
Poor Prognosis ◽  
Cell Metabolism ◽  
Oxygen Species ◽  
Chemotherapeutic Drugs ◽  
Cell Resistance ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway ◽  
Tumor Relapse ◽  
Increased Sensitivity

Cancer stem cells (CSC) are associated with the mechanisms of chemoresistance to different cytotoxic drugs or radiotherapy, as well as with tumor relapse and a poor prognosis. Various studies have shown that mitochondria play a central role in these processes because of the ability of this organelle to modify cell metabolism, allowing survival and avoiding apoptosis clearance of cancer cells. Thus, the whole mitochondrial cycle, from its biogenesis to its death, either by mitophagy or by apoptosis, can be targeted by different drugs to reduce mitochondrial fitness, allowing for a restored or increased sensitivity to chemotherapeutic drugs. Once mitochondrial misbalance is induced by a specific drug in any of the processes of mitochondrial metabolism, two elements are commonly boosted: an increment in reactive nitrogen/oxygen species and, subsequently, activation of the intrinsic apoptotic pathway.

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