Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine

Guo, Yan; Li, Xian; Sun, Xia; Wang, Jiancai; Xu, Yang; Zhou, Xin; Liu, Xinping; Li, Wenchao; Yuan, Jianlin; Yao, Libo; Li, Xia; Shen, Lan

doi:10.7150/ijbs.35094

Cited by 41 publications

(40 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The included studies were published from 2012 to 2019 with a total of 1980 cancer patients from China, [ 20 – 25 , 28 – 30 ] Korea, [ 26 , 27 , 31 ] and Japan. [ 18 ] Among all study cohorts, 2 evaluated colorectal cancer, [ 20 , 26 ] breast cancer, [ 24 , 31 ] and renal cell carcinoma, [ 27 , 28 ] and single studies focused on hepatocellular carcinoma, [ 21 ] cholangiocarcinoma, [ 22 ] prostate cancer, [ 25 ] gastric carcinomas, [ 23 ] pancreatic cancer, [ 18 ] lung cancer, [ 30 ] and gallbladder carcinoma. [ 29 ] The sample size ranged from 60 to 316.…”

Section: Resultsmentioning

confidence: 99%

Low NDRG2 expression predicts poor prognosis in solid tumors

et al. 2020

Medicine

View full text Add to dashboard Cite

Background: As a member of the N-myc down-regulated gene family, N-Myc downstream-regulated gene 2 (NDRG2) contributes to the tumorigenesis of various types of cancers. However, the correlation between NDRG2 expression and the prognosis of solid tumor remains to be elucidated because of small sample sizes and inconsistent results in previous studies. In the present study, we conducted a systematic review and meta-analysis to explore the prognostic significance of NDRG2 in human solid tumors. Methods: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, and WanFang databases (up to April 2020) were searched for relevant studies that evaluated the impact of NDRG2 on clinical outcomes, including overall survival (OS), and disease-free survival (DFS), in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to assess the association between NDRG2 expression and the survival of patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to estimate the correlation between NDRG2 expression and clinicopathologic characteristics in the patients. Results: A total of 13 eligible studies with 1980 patients were included in this meta-analysis. Low NDRG2 expression was significantly associated with poor OS (HR = 1.96, 95% CI: 1.60–2.40, P < .001) and DFS (HR = 2.70, 95% CI: 1.42–5.13, P = .002) in solid tumor. Furthermore, low NDRG2 expression was related to some phenotypes of tumor aggressiveness, such as clinical stage (OR = 3.21, 95% CI: 1.96–5.26, P < .001), lymph node metastasis (OR = 2.14, 95% CI: 1.49–3.07, P < .001), and degree of differentiation (OR = 0.60, 95% CI: 0.45–0.81, P = .001). Conclusions: NDRG2 may be a meaningful biomarker of poor prognosis and a potential therapeutic target for human solid tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

Low NDRG2 expression predicts poor prognosis in solid tumors

et al. 2020

Medicine

View full text Add to dashboard Cite

show abstract

“…LDH is a key factor for HCC tumor proliferation and invasion. Analysis of HCC patients’ serum samples suggested the use of serum LDH as a prognostic factor [ 30 , 31 , 32 , 33 , 34 , 35 ]. High levels of MCT4 and CD147, a transmembrane glycoprotein able to induce matrix metalloprotease (MMP) production and to interact with MCT4 for lactate secretion, were detected in HCC tissues [ 36 , 37 , 38 , 39 ].…”

Section: Hcc and Glucose Metabolismmentioning

confidence: 99%

Glucose Metabolism and Oxidative Stress in Hepatocellular Carcinoma: Role and Possible Implications in Novel Therapeutic Strategies

Mossenta

Busato

et al. 2020

Cancers

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) metabolism is redirected to glycolysis to enhance the production of metabolic compounds employed by cancer cells to produce proteins, lipids, and nucleotides in order to maintain a high proliferative rate. This mechanism drives towards uncontrolled growth and causes a further increase in reactive oxygen species (ROS), which could lead to cell death. HCC overcomes the problem generated by ROS increase by increasing the antioxidant machinery, in which key mechanisms involve glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible transcription factor (HIF-1α). These mechanisms could represent optimal targets for innovative therapies. The tumor microenvironment (TME) exerts a key role in HCC pathogenesis and progression. Various metabolic machineries modulate the activity of immune cells in the TME. The deregulated metabolic activity of tumor cells could impair antitumor response. Lactic acid–lactate, derived from the anaerobic glycolytic rate of tumor cells, as well as adenosine, derived from the catabolism of ATP, have an immunosuppressive activity. Metabolic reprogramming of the TME via targeted therapies could enhance the treatment efficacy of anti-cancer immunotherapy. This review describes the metabolic pathways mainly involved in the HCC pathogenesis and progression. The potential targets for HCC treatment involved in these pathways are also discussed.

show abstract

“…60 Upregulation of LDHA and PDK synergistically promotes the production of lactate in HCC. 60,61 Monocarboxylate transporter (MCT) expression on tumor cell membranes is associated with lactate passive transport and prevents glycolytic tumor cells from intracellular lactate accumulation. 59,62 MCT1 and MCT4 are major proteins expressed in tumors.…”

Section: Acid-base Microenvironmentmentioning

confidence: 99%

<p>Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect</p>

Tian

Zhu

et al. 2020

CMAR

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a tumor that exhibits glucometabolic reprogramming, with a high incidence and poor prognosis. Usually, HCC is not discovered until an advanced stage. Sorafenib is almost the only drug that is effective at treating advanced HCC, and promising metabolism-related therapeutic targets of HCC are urgently needed. The "Warburg effect" illustrates that tumor cells tend to choose aerobic glycolysis over oxidative phosphorylation (OXPHOS), which is closely related to the features of the tumor microenvironment (TME). The HCC microenvironment consists of hypoxia, acidosis and immune suppression, and contributes to tumor glycolysis. In turn, the glycolysis of the tumor aggravates hypoxia, acidosis and immune suppression, and leads to tumor proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), invasion and metastasis. In 2017, a mechanism underlying the effects of gluconeogenesis on inhibiting glycolysis and blockading HCC progression was proposed. Treating HCC by increasing gluconeogenesis has attracted increasing attention from scientists, but few articles have summarized it. In this review, we discuss the mechanisms associated with the TME, glycolysis and gluconeogenesis and the current treatments for HCC. We believe that a treatment combination of sorafenib with TME improvement and/or anti-Warburg therapies will set the trend of advanced HCC therapy in the future.

show abstract

Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine

Cited by 41 publications

References 49 publications

Low NDRG2 expression predicts poor prognosis in solid tumors

Low NDRG2 expression predicts poor prognosis in solid tumors

Glucose Metabolism and Oxidative Stress in Hepatocellular Carcinoma: Role and Possible Implications in Novel Therapeutic Strategies

<p>Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect</p>

Contact Info

Product

Resources

About