scholarly journals The Expression Profile and Prognostic Significance of Metallothionein Genes in Colorectal Cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 3849 ◽  
Author(s):  
Kuo-Chen Hung ◽  
Tsui-Chin Huang ◽  
Chia-Hsiung Cheng ◽  
Ya-Wen Cheng ◽  
Ding-Yen Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Gene Signature ◽  
Mrna Levels ◽  
Aberrant Expression ◽  
Gene Markers ◽  
Highly Sensitive ◽  
First Time ◽  
Better Than

Colorectal cancer (CRC) is a heterogeneous disease resulting from the combined influence of many genetic factors. This complexity has caused the molecular characterization of CRC to remain uncharacterized, with a lack of clear gene markers associated with CRC and the prognosis of this disease. Thus, highly sensitive tumor markers for the detection of CRC are the most essential determinants of survival. In this study, we examined the simultaneous downregulation of the mRNA levels of six metallothionein (MT) genes in CRC cell lines and public CRC datasets for the first time. In addition, we detected downregulation of these six MT mRNAs’ levels in 30 pairs of tumor (T) and adjacent non-tumor (N) CRC specimens. In order to understand the potential prognostic relevance of these six MT genes and CRC, we presented a four-gene signature to evaluate the prognosis of CRC patients. Further discovery suggested that the four-gene signature (MT1F, MT1G, MT1L, and MT1X) predicted survival better than any combination of two-, three-, four-, five-, or six-gene models. In conclusion, this study is the first to report that simultaneous downregulation of six MT mRNAs’ levels in CRC patients, and their aberrant expression together, accurately predicted CRC patients’ outcomes.

scholarly journals Aberrant Expression of the Long Non-coding RNA GHRLOS and Its Prognostic Significance in Patients with Colorectal Cancer

2017 ◽  
Vol 8 (19) ◽  
pp. 4040-4047 ◽  
Author(s):  
Shuangjie Wu ◽  
Jun Liu ◽  
Xinhai Wang ◽  
Mengjun Li ◽  
Zongyou Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Aberrant Expression ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Significant and conflicting correlation of IL-9 with Prevotella and Bacteroides in human colorectal cancer

2020 ◽  
Author(s):  
E Niccolai ◽  
E Russo ◽  
S Baldi ◽  
F Ricci ◽  
G Nannini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Multinomial Regression ◽  
Tnf Α ◽  
Ifn Γ ◽  
Inflammatory Profile ◽  
Infiltrating Lymphocytes ◽  
First Time

ABSTRACTBackgroundColorectal cancer (CRC) is a widespread disease that represents an example of chronic inflammation-associated tumor. In fact, the immune system, besides protecting the host from developing tumors, can support the CRC progression. In this scenario, the gut microbiota (GM) is essential to modulate immune responses and a dysbiotic condition can favor chronic/abnormal immune activation that support the tumor growth. GM can elicit the production of cytokines, influencing the immunostimulatory or immunosuppressive reactions, such as the tendency to mount Th1, Th17, Tregs or Th9 responses that play different roles towards colon cancer. Paradigmatic is the role of IL-9 that can both promote tumor progression in hematological malignancies and inhibit tumorigenesis in solid cancers. Therefore, to investigate the microbiota-immunity axis in CRC patients is crucial to well understand the cancer development with positive relapses in prevention and treatment.AimThe cellular and molecular characterization of the immune response and the evaluation of GM composition in healthy and tumor mucosa, focusing on the correlation between cytokines’ profile and GM signature.MethodsWe collected tumoral (CRC) and healthy (CRC-S) mucosa samples of 45 CRC patients. For each sample, we characterized the Tissue Infiltrating Lymphocytes (TIL)’s subset profile and the GM composition. In addition, in 14 CRC patients, we evaluated the CRC and CRC-S molecular inflammatory response (26 cytokines/chemokines) and we correlated this profile with GM composition using the Dirichlet Multinomial Regression.ResultsThe analysis of T cells subsets distribution showed that CRC samples displayed higher percentages of Th17, Th2, Tregs, Tc17, Tc1/Tc17, and Tcreg, compared to CRC-S. Notably, also the number of Th9 was higher, even if not significantly, in CRC tissue compared to healthy one. In addition, we found that MIP-1α, IL-1β, IL-2, IP-10, IL-6, IL-8, IL-17A, IFN-γ, TNF-α, MCP-1, IL-1α, P-selectin and IL-9 were significantly increased in CRC compared to CRC-S. Moreover, the GM analysis revealed that CRC samples had significantly higher levels of Fusobacteria, Proteobacteria, Fusobacterium, Ruminococcus2 (Lachnospiraceae family) and Ruminococcus (Ruminococcaceae family) than CRC-S. Finally, we found that the abundance of Prevotella spp in CRC samples was negatively correlated with IL-17A and positively with IL-9. In addition, the abundance of Bacteroides and Escherichia/Shigella species in CRC samples showed a negative association with IL-9 and IP-10 respectively.ConclusionsOur data show a clear dissimilarity of inflammatory profile and GM composition between the tumor and the adjacent healthy tissue, displaying the generation of a peculiar CRC microenvironment. Interestingly, relating the tissue cytokine profile with the GM composition, we confirmed the presence of a bidirectional crosstalk between the immune response and the host’s commensal microorganisms; in detail, we documented for the first time that Prevotella spp. and Bacteroides spp. are correlated (positively and negatively, respectively) with the IL-9, whose role in CRC development is still debated.

scholarly journals An improved method for atmospheric <sup>14</sup>CO measurements

2021 ◽  
Vol 14 (3) ◽  
pp. 2055-2063
Author(s):  
Vasilii V. Petrenko ◽  
Andrew M. Smith ◽  
Edward M. Crosier ◽  
Roxana Kazemi ◽  
Philip Place ◽  
...  
Keyword(s):  
Sample Volume ◽  
Spatial And Temporal Variability ◽  
Low Latitude ◽  
Mauna Loa ◽  
Carbon 14 ◽  
Air Sample ◽  
Atmospheric 14Co ◽  
First Time ◽  
Better Than

Abstract. Important uncertainties remain in our understanding of the spatial and temporal variability of atmospheric hydroxyl radical concentration ([OH]). Carbon-14-containing carbon monoxide (14CO) is a useful tracer that can help in the characterization of [OH] variability. Prior measurements of atmospheric 14CO concentration ([14CO] are limited in both their spatial and temporal extent, partly due to the very large air sample volumes that have been required for measurements (500–1000 L at standard temperature and pressure, L STP) and the difficulty and expense associated with the collection, shipment, and processing of such samples. Here we present a new method that reduces the air sample volume requirement to ≈90 L STP while allowing for [14CO] measurement uncertainties that are on par with or better than prior work (≈3 % or better, 1σ). The method also for the first time includes accurate characterization of the overall procedural [14CO] blank associated with individual samples, which is a key improvement over prior atmospheric 14CO work. The method was used to make measurements of [14CO] at the NOAA Mauna Loa Observatory, Hawaii, USA, between November 2017 and November 2018. The measurements show the expected [14CO] seasonal cycle (lowest in summer) and are in good agreement with prior [14CO] results from another low-latitude site in the Northern Hemisphere. The lowest overall [14CO] uncertainties (2.1 %, 1σ) are achieved for samples that are directly accompanied by procedural blanks and whose mass is increased to ≈50 µgC (micrograms of carbon) prior to the 14C measurement via dilution with a high-CO 14C-depleted gas.

scholarly journals Prognostic significance of BRAF mutation-associated gene signature in colorectal cancer

2017 ◽  
Vol 28 ◽  
pp. v187
Author(s):  
J.E. Hwang ◽  
W.K. Bae ◽  
H-J. Shim ◽  
S.H. Cho ◽  
I.J. Chung ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Braf Mutation ◽  
Prognostic Significance ◽  
Gene Signature

scholarly journals Prognostic significance of macrosatellite instability in patients under 50 years of age suffering from colorectal cancer

2009 ◽  
Vol 62 (5-6) ◽  
pp. 217-223
Author(s):  
Atila Fenjvesi
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Significance ◽  
Young Patients ◽  
Dna Mismatch ◽  
Significant Difference ◽  
Sporadic Cases ◽  
Microsatellite Stability ◽  
Better Than

Introduction Colorectal cancer (CRC) can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. High-frequency microsatellite instability (MSI) occurs in approximately 15 percent of sporadic cases of CRCs. Many studies have well established that MSI, the hallmark of defective DNA mismatch repair, is associated with prolonged survival of CRC patients compared with tumors that are microsatellite stable. CRCs in patients under 50 years of age are rare and represent about 5% of the total number of tumors. The aim of this study was to analyze the prognostic significance of MSI in CRC patients younger than 50 at the time of diagnosis. Material and methods 31 patients with CRC under 50 years of age were tested for the presence of MSI, and compared with 35 patients aged 50 or more at the time of diagnosis. CRC-specific survival five-year- follow-up period was analyzed in relation to MSI status. Results The frequency of MSI among the young patients was 35.48%, which was significantly higher than the rate of 11.43% noted in older patients with CRCs (p<0.042). This study revealed no difference in survival in patients with CRCs aged less than 50 compared with those over 50 years of age. The five-years survival of young CRCs patients with MSI 81.82%, was better than that of the patients with cancers with microsatellite stability, 60%, but there was no significant difference in statistics. Discussion and conclusion In our study there was no statistically detectable significant difference between tumor microsatellite status and survival in young patients, although we confirmed the previous observations that MSI is associated with better prognosis. We found that the pathological stage of CRC was an independent and powerful predictor of the clinical outcome.

The Aggregation of Marginal Gains

2011 ◽  
Vol 93 (7) ◽  
pp. 236-237 ◽  
Author(s):  
Mike Parker
Keyword(s):  
Colorectal Cancer ◽  
Great Britain ◽  
Mortality Rates ◽  
Cancer Surgery ◽  
Colorectal Cancer Surgery ◽  
Unit Level ◽  
First Time ◽  
Better Than

In April 2011, a major paper in Gut analysed data from the National Cancer Intelligence Network (NCIN) and was able to provide for the first time risk-adjusted unit-level mortality rates for colorectal cancer surgery. This breakthrough study identified several outlying units – one of which (The Shrewsbury and Telford Hospital NHS Trust) was found to be doing significantly better than expected. Mike Parker, President of the Association of Coloproctology of Great Britain and Ireland, visited the trust to try to learn the secrets of their success.

scholarly journals Discovery and characterization of a sulfoquinovose mutarotase using kinetic analysis at equilibrium by exchange spectroscopy

2018 ◽  
Vol 475 (7) ◽  
pp. 1371-1383 ◽  
Author(s):  
Palika Abayakoon ◽  
James P. Lingford ◽  
Yi Jin ◽  
Christopher Bengt ◽  
Gideon J. Davies ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Active Sites ◽  
Glucuronic Acid ◽  
Chemical Exchange ◽  
Sequence Analyses ◽  
Uncharacterized Gene ◽  
Exchange Spectroscopy ◽  
First Time ◽  
Better Than

Bacterial sulfoglycolytic pathways catabolize sulfoquinovose (SQ), or glycosides thereof, to generate a three-carbon metabolite for primary cellular metabolism and a three-carbon sulfonate that is expelled from the cell. Sulfoglycolytic operons encoding an Embden–Meyerhof–Parnas-like or Entner–Doudoroff (ED)-like pathway harbor an uncharacterized gene (yihR in Escherichia coli; PpSQ1_00415 in Pseudomonas putida) that is up-regulated in the presence of SQ, has been annotated as an aldose-1-epimerase and which may encode an SQ mutarotase. Our sequence analyses and structural modeling confirmed that these proteins possess mutarotase-like active sites with conserved catalytic residues. We overexpressed the homolog from the sulfo-ED operon of Herbaspirillum seropedicaea (HsSQM) and used it to demonstrate SQ mutarotase activity for the first time. This was accomplished using nuclear magnetic resonance exchange spectroscopy, a method that allows the chemical exchange of magnetization between the two SQ anomers at equilibrium. HsSQM also catalyzed the mutarotation of various aldohexoses with an equatorial 2-hydroxy group, including d-galactose, d-glucose, d-glucose-6-phosphate (Glc-6-P), and d-glucuronic acid, but not d-mannose. HsSQM displayed only 5-fold selectivity in terms of efficiency (kcat/KM) for SQ versus the glycolysis intermediate Glc-6-P; however, its proficiency [kuncat/(kcat/KM)] for SQ was 17 000-fold better than for Glc-6-P, revealing that HsSQM preferentially stabilizes the SQ transition state.

scholarly journals An improved method for atmospheric <sup>14</sup>CO measurements

2020 ◽  
Author(s):  
Vasilii V. Petrenko ◽  
Andrew M. Smith ◽  
Edward M. Crosier ◽  
Roxana Kazemi ◽  
Philip Place ◽  
...  
Keyword(s):  
Sample Volume ◽  
Spatial And Temporal Variability ◽  
Low Latitude ◽  
Mauna Loa ◽  
Carbon 14 ◽  
Air Sample ◽  
Atmospheric 14Co ◽  
First Time ◽  
Better Than

Abstract. Important uncertainties remain in our understanding of the spatial and temporal variability of atmospheric hydroxyl radical concentration ([OH]). Carbon-14-containing carbon monoxide (14CO) is a useful tracer that can help in the characterization of [OH] variability. Prior measurements of atmospheric 14CO concentration ([14CO] are limited in both their spatial and temporal extent, partly due to the very large air sample volumes that have been required for measurements (500–1000 liters at standard temperature and pressure, L STP) and the difficulty and expense associated with the collection, shipment and processing of such samples. Here we present a new method that reduces the air sample volume requirement to &amp;approx; 90 L STP while allowing for [14CO] measurement uncertainties that are on par with or better than prior work (&amp;approx; 3 % or better, 1 σ). The method also for the first time includes accurate characterization of the overall procedural [14CO] blank associated with individual samples, a key improvement over prior atmospheric 14CO work. The method was used to make measurements of [14CO] at the NOAA Mauna Loa Observatory, Hawaii, USA, between November 2017 and November 2018. The measurements show the expected [14CO] seasonal cycle (lowest in summer) and are in good agreement with prior [14CO] results from another low-latitude site in the Northern Hemisphere. The lowest overall [14CO] uncertainties (2.1 %, 1 σ) are achieved for samples that are directly accompanied by procedural blanks and whose mass is increased to &amp;approx; 50 micrograms of carbon (µgC) prior to the 14C measurement via dilution with a high-CO, 14C-depleted gas.

scholarly journals Focused screening reveals functional effects of microRNAs differentially expressed in colorectal cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Danuta Sastre ◽  
João Baiochi ◽  
Ildercilio Mota de Souza Lima ◽  
Felipe Canto de Souza ◽  
Amanda Cristina Corveloni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Antitumoral Activity ◽  
Pathway Enrichment Analysis ◽  
Mrna Levels ◽  
Aberrant Expression ◽  
Apoptosis Pathway ◽  
Mrna Targets ◽  
Intrinsic Apoptosis Pathway ◽  
Hct116 Cells

Abstract Background Colorectal cancer (CRC) is still a leading cause of death worldwide. Recent studies have pointed to an important role of microRNAs in carcinogenesis. Several microRNAs are described as aberrantly expressed in CRC tissues and in the serum of patients. However, functional outcomes of microRNA aberrant expression still need to be explored at the cellular level. Here, we aimed to investigate the effects of microRNAs aberrantly expressed in CRC samples in the proliferation and cell death of a CRC cell line. Methods We transfected 31 microRNA mimics into HCT116 cells. Total number of live propidium iodide negative (PI-) and dead (PI+) cells were measured 4 days post-transfection by using a high content screening (HCS) approach. HCS was further used to evaluate apoptosis (via Annexin V and PI staining), and to discern between intrinsic and extrinsic apoptotic pathways, by detecting cleaved Caspase 9 and 8, respectively. To reveal mRNA targets and potentially involved mechanisms, we performed microarray gene expression and functional pathway enrichment analysis. Quantitative PCR and western blot were used to validate potential mRNA targets. Results Twenty microRNAs altered the proliferation of HCT116 cells in comparison to control. miR-22-3p, miR-24-3p, and miR-101-3p significantly repressed cell proliferation and induced cell death. Interestingly, all anti-proliferative microRNAs in our study had been previously described as poorly expressed in the CRC samples. Predicted miR-101-3p targets that were also downregulated by in our microarray were enriched for genes associated with Wnt and cancer pathways, including MCL-1, a member of the BCL-2 family, involved in apoptosis. Interestingly, miR-101-3p preferentially downregulated the long anti-apoptotic MCL-1 L isoform, and reduced cell survival specifically by activating the intrinsic apoptosis pathway. Moreover, miR-101-3p also downregulated IL6ST, STAT3A/B, and MYC mRNA levels, genes associated with stemness properties of CRC cells. Conclusions microRNAs upregulated in CRC tend to induce proliferation in vitro, whereas microRNAs poorly expressed in CRC halt proliferation and induce cell death. We provide novel evidence linking preferential inhibition of the anti-apoptotic MCL-1 L isoform by miR-101-3p and consequent activation of the intrinsic apoptotic pathway as potential mechanisms for its antitumoral activity, likely due to the inhibition of the IL-6/JAK/STAT signaling pathway.

scholarly journals Construction of an RNA Binding Protein-based Model for Prognosis Prediction of Colorectal Cancer

2020 ◽  
Author(s):  
Ting li ◽  
Wenjia Hui ◽  
Halina Halike ◽  
Feng Gao
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Risk Score ◽  
Rna Binding ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Signature ◽  
Independent Prognostic Factor ◽  
Time Dependent ◽  
Incidence And Mortality

Abstract Background: Colorectalcancer (CRC) is a prevalent gastrointestinal tumor with high incidence and mortality. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. This study aimed to develop and validate new biomarkers related to CRC prognosis by a series of bioinformatics analysis.Methods: We mined the gene expression data of 510 CRC samples from The Cancer Genome Atlas (TCGA) database, differentially expressed genes were screened and prognosis-related genes were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature,The test set was used to validate the RBPs risk score model.Survival analysis was carried out to determine the independent prognostic significance of the signature. A nomogram combined with the gene signature was constructed.Results: A total of 224 aberrantly expressed RBPs were obtained, comprising 78 downregulated and 146 upregulatedRBPs. 13 RBPs with p < 0.005 were revealed in univariateCox regression analysis of train group, then stepwise multivariate Cox regression was applied for constituting an eight- RBP (BRCA1, TERT, TDRD7, PPARGC1A, LUZP4, CELF4, ZC3H12C, PNLDC1) signature prognostic biomarkers. Further analysis demonstrated that high risk score for patients was significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.730 at 5 years. The signature-based risk score was an independent prognostic factor in CRC patients. We also established a nomogram based on eight RBPs and internal validation in the train set, which displayed a favorable discriminating ability for Colorectal cancer.Conclusions: The established eight-RBP signature may serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of CRC patients. However, the specific biological mechanism needs further verification.

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