Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival.
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ABSTRACT:
SUBMITTER: Sirnio P
PROVIDER: S-EPMC6342921 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundInflammation contributes to the pathogenesis of colorectal cancer (CRC), and cytokine levels are altered during colorectal carcinogenesis.MethodsThe serum levels of 13 cytokines and their relation to clinical and pathological parameters, and systemic inflammatory response (mGPS, CRP and neutrophil-lymphocyte ratio), were analysed from a prospective series of 148 CRC patients and 86 healthy age- and sex-matched controls.ResultsCRC patients had higher serum platelet-derived growth factor, interleukin (IL)-6, IL-7, and IL-8 levels and lower monocyte chemotactic protein-1 (MCP-1) levels than the controls. A logistic regression model for discriminating the patients from the controls - including the five most predictive cytokines (high IL-8, high IL-6, low MCP-1, low IL-1ra, and low IP-10) - yielded an area under curve value of 0.890 in receiver operating characteristics analysis. Serum cytokines showed distinct correlation with other markers of systemic inflammatory response, and advanced CRCs were associated with higher levels of IL-8, IL-1ra, and IL-6. A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu.ConclusionCRC is associated with extensive alterations in serum cytokine environment, highlighting the importance of studying relative cytokine level alterations. Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed.
| S-EPMC3493870 | biostudies-literature
Project description:BACKGROUND: Presently, colorectal cancer (CRC) is staged preoperatively by radiographic tests, and postoperatively by pathological evaluation of available surgical specimens. However, present staging methods do not accurately identify occult metastases. This has a direct effect on clinical management. Early identification of metastases isolated to the liver may enable surgical resection, whereas more disseminated disease may be best treated with palliative chemotherapy. METHODS: Sera from 103 patients with colorectal adenocarcinoma treated at the same tertiary cancer center were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Metabolic profiling was done using both supervised pattern recognition and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profiles generated from each platform were compared between the following groups: locoregional CRC (N = 42); liver-only metastases (N = 45); and extrahepatic metastases (N = 25). RESULTS: The serum metabolomic profile associated with locoregional CRC was distinct from that associated with liver-only metastases, based on 1H NMR spectroscopy (P = 5.10 × 10-7) and GC-MS (P = 1.79 × 10-7). Similarly, the serum metabolomic profile differed significantly between patients with liver-only metastases and with extrahepatic metastases. The change in metabolomic profile was most markedly demonstrated on GC-MS (P = 4.75 × 10-5). CONCLUSIONS: In CRC, the serum metabolomic profile changes markedly with metastasis, and site of disease also appears to affect the pattern of circulating metabolites. This novel observation may have clinical utility in enhancing staging accuracy and selecting patients for surgical or medical management. Additional studies are required to determine the sensitivity of this approach to detect subtle or occult metastatic disease.
| S-EPMC3506908 | biostudies-other
Project description:We sought to identify a serum miRNA expression profile to improve disease surveillance and to predict post-operative disease recurrence for stage II/III colorectal cancer (CRC) patients. Using the TaqMan Low-Density Array (TLDA), we performed an initial survey to analyze 749 miRNAs in the pooled serum of 20 paired pre- and post-operative CRC patients and 20 matched normal subjects. Using individual RT-qPCR verification in 175 stage II/III CRC patients, we identified that miR-145, miR-106a and miR-17-3p were significantly differentially expressed between pre- and post-operative CRC patients and between pre-operative CRC patients and normal controls (P?<?0.0001). The area under the ROC curve (AUC) for the three-miRNA panel was 0.886 (95% CI 0.850-0.921) for discriminating between pre-operative CRC patients and normal subjects and 0.850 (95% CI 0.809-0.891) for discriminating between pre- and post-operative CRC patients. Furthermore, using the Kaplan-Meier method and Cox proportional hazards analysis, we found that miR-17-3p and miR-106a were powerful and independent prognostic indicators and that high levels of these miRNAs were associated with shorter disease-free survival (DFS) (P?<?0.0001 for miR-17-3p and P?=?0.001 for miR-106a). The present study reveals novel serum-miRNA-based biomarkers for monitoring tumor dynamics as well as for predicting disease recurrence in patients with stage II/III CRC.
| S-EPMC4528229 | biostudies-literature
Project description:Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain1,2. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not restricted to tumours, but are also found in other tissue microenvironments, complicating treatment3,4. Despite great efforts to define inflammatory processes in the tumour microenvironment, the understanding of tumour-unique immune alterations is limited by a knowledge gap regarding the immune cell populations in inflamed human tissues. Here, in an effort to identify such tumour-enriched immune alterations, we used complementary single-cell analysis approaches to interrogate the immune infiltrate in human head and neck squamous cell carcinomas and site-matched non-malignant, inflamed tissues. Our analysis revealed a large overlap in the composition and phenotype of immune cells in tumour and inflamed tissues. Computational analysis identified tumour-enriched immune cell interactions, one of which yields a large population of regulatory T (Treg) cells that is highly enriched in the tumour and uniquely identified among all haematopoietically-derived cells in blood and tissue by co-expression of ICOS and IL-1 receptor type 1 (IL1R1). We provide evidence that these intratumoural IL1R1+ Treg cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1- Treg cells. In addition to identifying extensive immunological congruence between inflamed tissues and tumours as well as tumour-specific changes with direct disease relevance, our work also provides a blueprint for extricating disease-specific changes from general inflammation-associated patterns.
| S-EPMC9132772 | biostudies-literature
Project description:Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC.
| S-EPMC5828217 | biostudies-literature
Project description:BACKGROUND:Matrix metalloproteinase-8 (MMP-8) is a protease mainly expressed by neutrophils that cleaves numerous substrates, including collagens and cytokines. We have previously shown that serum MMP-8 levels increase in colorectal cancer (CRC) and correlate with distant metastasis. However, short follow-up in our prospective cohort did not enable survival analyses at the time of the first publication. METHODS:Preoperative serum MMP-8 levels were measured by immunofluorometric assay in 271 CRC patients and related to clinicopathological parameters, markers of systemic inflammation (modified Glasgow Prognostic Score, mGPS; serum levels of C-reactive protein (CRP), albumin and 13 cytokines), the density of six types of tumour-infiltrating immune cells and survival. RESULTS:Increased MMP-8 levels associated with higher mGPS and higher serum levels of CRP and several cytokines, including IL-1ra, IL-7 and IL-8 (p?<?0.001 for all). Serum MMP-8 negatively correlated with tumour-infiltrating mast cells (invasive margin: p?=?0.005, tumour centre: p?=?0.010). The patients with high-serum MMP-8 levels (>100?ng/mL) had poor cancer-specific survival, independent of tumour stage, grade, lymphatic invasion, patient age, BRAF VE1 immunohistochemistry, mismatch repair deficiency, Immunoscore and mGPS (multivariate HR 2.12, 95% CI 1.21-3.71, p?=?0.009). CONCLUSIONS:High-serum MMP-8 levels are associated with systemic inflammation and adverse outcome in CRC.
| S-EPMC6048114 | biostudies-literature
Project description:The pandemic of the coronavirus disease (COVID-19) caused by SARS-CoV-2 affects millions of people worldwide. There are still many unknown aspects to this infection which affects the whole world. In addition, the potential impacts caused by this infection are still unclear. Amino acid metabolism, in particular, contains significant clues in terms of the development and prevention of many diseases. Therefore, this study aimed to compare amino acid profile of COVID-19 and healthy subject. In this study, the amino acid profiles of patients with asymptomatic, mild, moderate, and severe/critical SARS-CoV-2 infection were scanned with LC-MS/MS. The amino acid profile encompassing 30 amino acids in 142 people including 30 control and 112 COVID-19 patients was examined. 20 amino acids showed significant differences when compared to the control group in COVID-19 patient groups with different levels of severity in the statistical analyses conducted. It was detected that the branched-chain amino acids (BCAAs) changed in correlation with one another, and L-2-aminobutyric acid and L-phenylalanine had biomarker potential for COVID-19. Moreover, it was concluded that L-2-aminobutyric acid could provide prognostic information about the course of the disease. We believe that a new viewpoint will develop regarding the diagnosis, treatment, and prognosis as a result of the evaluation of the serum amino acid profiles of COVID-19 patients. Determining L-phenylalanine and L-2-aminobutyric levels can be used in laboratories as a COVID-19-biomarker. Also, supplementing COVID patients with taurine and BCAAs can be beneficial for treatment protocols.
| S-EPMC8487804 | biostudies-literature
Project description:The correlation of low serum albumin with mortality in patients with chronic kidney disease (CKD) is partly linked to its association with systemic inflammation. However, it is not clear to what extent albumin's correlation with mortality depends on concomitant systemic inflammation. Here we addressed this question in patients with CKD stage 5.Serum albumin (S-Alb), systemic inflammation (high-sensitive C-reactive protein, hsCRP), cardiovascular disease (CVD) and nutritional status (subjective global assessment, SGA) were assessed at baseline in 822 patients: 523 incident dialysis patients, 212 prevalent hemodialysis (HD) and 87 prevalent peritoneal dialysis (PD) patients. Patients were divided into four groups according to hsCRP and S-Alb in each cohort: Group 1 -normal S-Alb and normal hsCRP (reference); Group 2 -low S-Alb and normal hsCRP; Group 3-normal S-Alb and high hsCRP; Group 4-low S-Alb and high hsCRP. Survival over 60 months was analyzed.In Cox analysis, Group 4 had an increased mortality risk (adjusted Hazard ratio (95% confidence interval): 1.62 (1.06-2.47); p = 0.02) whereas the augmented mortality risks for Groups 2 and 3 in univariate analyses were not significant after adjustments for age, gender, blood pressure, diabetes mellitus, smoking, SGA, renal function and renal replacement technique.Whereas mortality risk was increased in CKD stage 5 patients with low S-Alb and high CRP, it was not increased in patients with low S-Alb and normal CRP. Our observation suggests that inflammatory status should be taken into account when using S-albumin for risk assessment in CKD stage 5 patients.
| S-EPMC5752034 | biostudies-literature
Project description:Organoids have extensive applications in many fields ranging from modelling human development and disease, personalised medicine, drug screening, etc. Moreover, in the last few years, several studies have evaluated the capacity of organoids as transplantation sources for therapeutic approaches and regenerative medicine. Nevertheless, depending on the origin of the cells and anatomical complications, an organoid transplant may make tissue regeneration difficult. However, some essential aspects of organoids including the morphological alterations and the growth pattern of the matched tumour and their healthy derived organoids have received less attention. Therefore, the current work focused on culturing matched healthy and tumour organoids from the same patient with colorectal cancer (CRC) and assessed their timed growth and structural differences on a daily basis. The healthy organoids underwent proliferation and branching morphogenesis, while the tumour organoids did not follow the same pattern, and the majority of them developed cystic structures instead. However, the number and size of tumour organoids were different from one patient to another. The differential morphological changes of the healthy versus human colonic tumour organoids likely linked to distinct molecular and cellular events during each day. Thus, while their specific structural features provide valuable in vitro models to study various aspects of human intestinal/colon tissue homeostasis and CRC which avoid or replace the use of animals in research, this model may also hold a great promise for the transplantation and regenerative medicine applications.
| S-EPMC5828197 | biostudies-literature
Project description:Deficiency of vitamin D is associated with increased risk of several types of cancer including colorectal cancer (CRC). However, factors contributing to low levels of 25-hydroxyvitamin D [25(OH)D] in CRC are not clear. Therefore, in this study serum 25(OH)D levels in 117 CRC patients and 86 controls were analyzed and correlated with the clinicopathological data including morphological subtype (serrated or conventional), quantity of tumor infiltrating immune cells, levels of systemic inflammatory markers, and disease outcome. We found that the patients had lower serum 25(OH)D levels compared to the controls. Interestingly, among the patients mismatch repair deficiency, serrated morphology, and high body mass index associated with lowest serum 25(OH)D levels. In addition, patients operated in summer or autumn had higher serum 25(OH)D levels. Furthermore, serum 25(OH)D levels inversely correlated with several systemic inflammatory markers, e.g. serum C reactive protein, but did not associate with prognosis. Mechanism leading to vitamin D deficiency in these patients are not clear but could be related to the effects of systemic inflammation. Longitudinal studies are warranted to assess vitamin D deficiency as a potential risk factor for serrated colorectal polyps and adenocarcinoma.
| S-EPMC5098144 | biostudies-literature