Clinical Significance of Serum Glutamine Level in Patients with Colorectal Cancer

Ling, Hang; Pan, Yu‐Hwa; Fan, Chung-Wei; Tseng, Wen-Ko; Huang, Jen‐Seng; Wu, Tsung‐Han; Chou, Wen‐Chi; Wang, Cheng‐Hsu; Yeh, Kun‐Yun; Chang, Pei‐Hung

doi:10.3390/nu11040898

Cited by 30 publications

(36 citation statements)

References 43 publications

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“…Contradictory findings are reported in the literature with injury severity indicators not strongly associated with circulating glutamine in some cases [15,16] and positively associated in other cases [23]. The correlation with markers of infection and inflammation has been confirmed by others, with lower plasma glutamine levels found to be associated with lower albumin levels [17,18], higher CRP levels [18,22], and higher circulating IL-1β and IL-6 levels [18]. In some studies, low glutamine levels were also associated with renal impairment, but this was not confirmed in other studies [16].…”

Section: Discussionmentioning

confidence: 69%

“…We noted that patients with a low baseline glutamine had a higher ICU mortality, but this association was not significant. Again, contradictory findings are reported in the literature, with no strong link between glutamine levels and mortality [26], mortality associated with low baseline glutamine levels [17,18], or mortality associated with either low or high glutamine levels [15,16].…”

Section: Discussionmentioning

confidence: 94%

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Plasma Glutamine Levels in Relation to Intensive Care Unit Patient Outcome

2020

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Low and high plasma glutamine levels are associated with increased mortality. This study aimed to measure glutamine levels in critically ill patients admitted to the intensive care unit (ICU), correlate the glutamine values with clinical outcomes, and identify proxy indicators of abnormal glutamine levels. Patients were enrolled from three ICUs in South Africa, provided they met the inclusion criteria. Clinical and biochemical data were collected. Plasma glutamine was categorized as low (<420 µmol/L), normal (420-700 µmol/L), or high (>700 µmol/L). Three hundred and thirty patients (median age 46.8 years, 56.4% male) were enrolled (median APACHE II score) 18.0 and SOFA) score 7.0). On admission, 58.5% had low (median 299.5 µmol/L) and 14.2% high (median 898.9 µmol/L) plasma glutamine levels. Patients with a diagnosis of polytrauma and sepsis on ICU admission presented with the lowest, and those with liver failure had the highest glutamine levels. Admission low plasma glutamine was associated with higher APACHE II scores (p = 0.003), SOFA scores (p = 0.003), C-reactive protein (CRP) values (p < 0.001), serum urea (p = 0.008), and serum creatinine (p = 0.023) and lower serum albumin (p < 0.001). Low plasma glutamine was also associated with requiring mechanical ventilation and receiving nutritional support. However, it was not significantly associated with length of stay or mortality. ROC curve analysis revealed a CRP threshold value of 87.9 mg/L to be indicative of low plasma glutamine levels (area under the curve (AUC) 0.7, p < 0.001). Fifty-nine percent of ICU patients had low plasma glutamine on admission, with significant differences found between diagnostic groupings. Markers of infection and disease severity were significant indicators of low plasma glutamine.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 94%

Plasma Glutamine Levels in Relation to Intensive Care Unit Patient Outcome

2020

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“…In this regard, the enzyme glutaminase (GLS1), which catalyzes the first step of glutamine metabolism, is highly expressed in colon cancer and linked to significantly reduced survival [ 54 , 55 ]. Besides, recent epidemiological studies correlate low serum glutamine levels (indicative of higher glutamine consumption) with poorer overall survival in colorectal cancer patients [ 56 ]. Even though many studies have been conducted to unveil the metabolism of glutamine in tumors, there is much yet to be explored.…”

Section: Discussionmentioning

confidence: 99%

Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

et al. 2021

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Nucleotide pools need to be constantly replenished in cancer cells to support cell proliferation. The synthesis of nucleotides requires glutamine and 5-phosphoribosyl-1-pyrophosphate produced from ribose-5-phosphate via the oxidative branch of the pentose phosphate pathway (ox-PPP). Both PPP and glutamine also play a key role in maintaining the redox status of cancer cells. Enhanced glutamine metabolism and increased glucose 6-phosphate dehydrogenase (G6PD) expression have been related to a malignant phenotype in tumors. However, the association between G6PD overexpression and glutamine consumption in cancer cell proliferation is still incompletely understood. In this study, we demonstrated that both inhibition of G6PD and glutamine deprivation decrease the proliferation of colon cancer cells and induce cell cycle arrest and apoptosis. Moreover, we unveiled that glutamine deprivation induce an increase of G6PD expression that is mediated through the activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2). This crosstalk between G6PD and glutamine points out the potential of combined therapies targeting oxidative PPP enzymes and glutamine catabolism to combat colon cancer.

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“…For example, IL-6 stimulates liver production of CRP and other acute phase proteins, thus increasing the demand for amino acids against a background of limited intake. In particular, low circulating glutamine concentrations (the most abundant amino acid in plasma) have been reported to be associated with hypoalbuminemia, a low SMI (major source of glutamine) and poorer survival in patients with colorectal cancer [29][30][31][32]. Therefore, it would appear the most abundant circulating amino acid (glutamine), circulating protein (albumin) and body protein are linked in a chronic systemic inflammatory response and that albumin reflects the inter-organ amino acid flux during the chronic systemic inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Hypoalbuminemia Reflects Nutritional Risk, Body Composition and Systemic Inflammation and Is Independently Associated with Survival in Patients with Colorectal Cancer

Almasaudi

Dolan

Edwards

et al. 2020

Cancers

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It has long been recognized that albumin has prognostic value in patients with cancer. However, although the Global Leadership Initiative on Malnutrition GLIM criteria (based on five diagnostic criteria, three phenotypic criteria and two etiologic criteria) recognize inflammation as an important etiologic factor in malnutrition, there are limited data regarding the association between albumin, nutritional risk, body composition and systemic inflammation, and whether albumin is associated with mortality independent of these parameters. The aim of this study was to examine the relationship between albumin, nutritional risk, body composition, systemic inflammation, and outcomes in patients with colorectal cancer (CRC). A retrospective cohort study (n = 795) was carried out in which patients were divided into normal and hypoalbuminaemic groups (albumin <35 g/L) in the presence and absence of a systemic inflammatory response C-reactive protein (CRP >10 and <10 mg/L, respectively). Post-operative complications, severity of complications and mortality were considered as outcome measures. Categorical variables were analyzed using Chi-square test χ 2or linear-by-linear association. Survival data were analyzed using univariate and multivariate Cox regression. In the presence of a systemic inflammatory response, hypoalbuminemia was directly associated with Malnutrition Universal Screening Tool MUST (p < 0.001) and inversely associated with Body Mass Index BMI (p < 0.001), subcutaneous adiposity (p < 0.01), visceral obesity (p < 0.01), skeletal muscle index (p < 0.001) and skeletal muscle density (p < 0.001). There was no significant association between hypoalbuminemia and either the presence of complications or their severity. In the absence of a systemic inflammatory response (n = 589), hypoalbuminemia was directly associated with MUST (p < 0.05) and inversely associated with BMI (p < 0.01), subcutaneous adiposity (p < 0.05), visceral adiposity (p < 0.05), skeletal muscle index (p < 0.01) and skeletal muscle density (p < 0.001). Hypoalbuminemia was, independently of inflammatory markers, associated with poorer cancer-specific and overall survival (both p < 0.001). The results suggest that hypoalbuminemia in patients with CRC reflects both increased nutritional risk and greater systemic inflammatory response and was independently associated with poorer survival in patients with CRC.

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Clinical Significance of Serum Glutamine Level in Patients with Colorectal Cancer

Cited by 30 publications

References 43 publications

Plasma Glutamine Levels in Relation to Intensive Care Unit Patient Outcome

Plasma Glutamine Levels in Relation to Intensive Care Unit Patient Outcome

Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

Hypoalbuminemia Reflects Nutritional Risk, Body Composition and Systemic Inflammation and Is Independently Associated with Survival in Patients with Colorectal Cancer

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