scholarly journals Key biomarkers within the colorectal cancer related inflammatory microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Valentin Calu ◽  
Adriana Ionescu ◽  
Loredana Stanca ◽  
Ovidiu Ionut Geicu ◽  
Florin Iordache ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Staging ◽  
Pearson Correlation ◽  
Tumor Resection ◽  
Correlation Coefficients ◽  
Tumor Stage ◽  
Magnetic Bead ◽  
Tissue Expression ◽  
Tissue Samples ◽  
Inflammatory Microenvironment

AbstractTherapeutic approaches focused on the inflammatory microenvironment are currently gaining more support, as biomolecules involved in the inflammatory colorectal cancer (CRC) tumor microenvironment are being explored. We analyzed tumor and paired normal tissue samples from CRC patients (n = 22) whom underwent tumor resection surgery. We assessed 39 inflammation-involved biomolecules (multiplex magnetic bead-based immunoassay), CEA and CA19-9 (ELISA assay) and the tissue expression levels of occludin and also pErk, STAT1 and STAT3 transcriptional factors (western blot). Tumor staging has been established by histopathological evaluation of HE stained tumor tissue sections. We report 32 biomarkers displaying statistically significant differences in tumor vs. control. Additionally, positive statistical biomarker correlations were found between MMP2–IL8 and BAFF–IL8 (Pearson correlation coefficients > 0.751), while APRIL–MMP2, APRIL–BAFF and APRIL–IL8 were negatively correlated (correlation coefficients < − 0.650). While APRIL, BAFF, IL8 and MMP2 did not modulate with tumor stage, they were inversely related to the immune infiltrate level and CD163 tissue expression. We conclude that the significantly decreased APRIL and increased BAFF, IL8 and MMP2 expression were tumor-specific and deserve consideration in the development of new treatments. Also, the positive correlation between Chitinase 3-like 1 and IL8 (0.57) or MMP2 (0.50) suggest a role in tumor growth and metastasis pathways.

scholarly journals Key Biomarkers Within the Colorectal Cancer Related Inflammatory Microenvironment

2020 ◽  
Author(s):  
Valentin Calu ◽  
Adriana Ionescu ◽  
Loredana Stanca ◽  
Ovidiu Geicu ◽  
Florin Iordache ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Resection ◽  
Surgical Care ◽  
Magnetic Bead ◽  
Inflammatory Factors ◽  
Tissue Samples ◽  
Inflammatory Microenvironment ◽  
Starting Point ◽  
Cancer Tumor

Abstract The necessity of therapeutic approaches focused on the inflammatory microenvironment of colorectal cancer (CRC) is becoming more and more apparent, both in order to improve post-surgical care and subsequent therapeutic strategies, and also for better quality of life for the patients. We have investigated a panel of 39 inflammatory factors using a multiplex magnetic bead-based immunoassay, in relation with CEA and CA19-9, classical tumor markers and the expression levels of pErk, occludin, and STAT1 and STAT3 transcriptional factors. Within the tumor and paired normal tissue samples collected during tumor resection surgery, we have identified 32 biomarkers displaying statistically significant differences. Several relevant correlations have been observed in a combined multi-type correlation matrix. Chitinase 3-like 1 seems to be a trigger for activation pathways for tumor growth and metastasis. Through IL-22 and IL1β, IL-8 correlates indirectly with CA19-9 and CEA, respectively. We also emphasize the diminished APRIL and high BAFF levels in colon cancer tumor tissue, which is quite unique. The strong correlation between APRIL, BAFF, IL-8 and MMP2 recommends these as combined targets in immunotherapies for colon cancer treatment, and indicates the marker quartet may serve as a starting point in colon cancer screening.

The relationship between the degree of aberrant methylation in colorectal cancer tissue and appearance of tumor-derived DNA in blood.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 579-579
Author(s):  
Erin L Symonds ◽  
Susanne Kartin Pedersen ◽  
Rohan Baker ◽  
Scott Mansfield ◽  
Dawn Bastin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Residual Disease ◽  
Tumor Staging ◽  
Tumor Resection ◽  
Tumor Stage ◽  
Circulating Tumor Dna ◽  
Early Event ◽  
Cancer Tissue ◽  
Aberrant Methylation ◽  
Secondary Tumors

579 Background: We have developed a blood test for colorectal cancer (CRC) detecting circulating tumor DNA (ctDNA) by measuring the presence of methylated BCAT1 and IKZF1. This study aimed to compare the levels of methylated BCAT1/IKZF1 in tissue from patients with colorectal cancer to those in blood before and after tumor resection. Methods: 80 people with invasive CRC had blood collected prior to resection. Tumor and adjacent non-tumor colorectal tissue was collected at surgery. Five patients had tissue collected from secondary cancers in the liver. Additional blood samples were collected within a year of surgery from 45 of these patients. DNA was extracted from all samples and assayed for methylated BCAT1 and IKZF1 DNA. Results: The median % BCAT1 and IKZF1 methylation in colorectal tissues were 45.7% and 59.9% (tumor), and 4.8% and 0% (non-tumor), p < 0.001. Median methylation levels in secondary tumors of the liver were 4.9% for BCAT1 and 29.5% for IKZF1, compared to 0% for both biomarkers in non-tumor liver tissue (p < 0.01). The methylation levels did not differ across CRC stages (p > 0.05), whereas the detection of ctDNA in the blood was significantly associated with tumor staging (p < 0.01). Of the 21 ctDNA positive CRC patients, 18 (86%) tested negative post resection. Of the 3 that remained blood positive post resection, further cancers were confirmed in two (one with recurrence in the lung, one with thyroid cancer). Conclusions: Aberrant BCAT1 and IKZF1 methylation is an early event in CRC development and is localised to the tumor tissue. Methylated BCAT1 and IKZF1 in blood are dependent on tumor stage and measuring minimal residual disease by detecting ctDNA based on methylated BCAT1 and IKZF1 may inform completeness of tumor resection.

scholarly journals Investigating Serum and Tissue Expression Identified a Cytokine/Chemokine Signature as a Highly Effective Melanoma Marker

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3680
Author(s):  
Marco Cesati ◽  
Francesca Scatozza ◽  
Daniela D’Arcangelo ◽  
Gian Carlo Antonini-Cappellini ◽  
Stefania Rossi ◽  
...  
Keyword(s):  
Single Molecule ◽  
Learning Algorithm ◽  
Profile Analysis ◽  
Pearson Correlation ◽  
Tissue Expression ◽  
Support Vector ◽  
Expression Data ◽  
Serum Samples ◽  
Tissue Samples ◽  
Mortality And Morbidity

The identification of reliable and quantitative melanoma biomarkers may help an early diagnosis and may directly affect melanoma mortality and morbidity. The aim of the present study was to identify effective biomarkers by investigating the expression of 27 cytokines/chemokines in melanoma compared to healthy controls, both in serum and in tissue samples. Serum samples were from 232 patients recruited at the IDI-IRCCS hospital. Expression was quantified by xMAP technology, on 27 cytokines/chemokines, compared to the control sera. RNA expression data of the same 27 molecules were obtained from 511 melanoma- and healthy-tissue samples, from the GENT2 database. Statistical analysis involved a 3-step approach: analysis of the single-molecules by Mann–Whitney analysis; analysis of paired-molecules by Pearson correlation; and profile analysis by the machine learning algorithm Support Vector Machine (SVM). Single-molecule analysis of serum expression identified IL-1b, IL-6, IP-10, PDGF-BB, and RANTES differently expressed in melanoma (p < 0.05). Expression of IL-8, GM-CSF, MCP-1, and TNF-α was found to be significantly correlated with Breslow thickness. Eotaxin and MCP-1 were found differentially expressed in male vs. female patients. Tissue expression analysis identified very effective marker/predictor genes, namely, IL-1Ra, IL-7, MIP-1a, and MIP-1b, with individual AUC values of 0.88, 0.86, 0.93, 0.87, respectively. SVM analysis of the tissue expression data identified the combination of these four molecules as the most effective signature to discriminate melanoma patients (AUC = 0.98). Validation, using the GEPIA2 database on an additional 1019 independent samples, fully confirmed these observations. The present study demonstrates, for the first time, that the IL-1Ra, IL-7, MIP-1a, and MIP-1b gene signature discriminates melanoma from control tissues with extremely high efficacy. We therefore propose this 4-molecule combination as an effective melanoma marker.

scholarly journals Metabolomic profile of colorectal cancer patients and its clinical implications

2020 ◽  
Vol 25 (6) ◽  
pp. 2045-2054
Author(s):  
CLAUDIU RĂCHIERIU ◽  
◽  
FLORIN GRAUR ◽  
EMIL MOIS ◽  
CARMEN SOCACIU ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Diagnosis ◽  
Biological Fluids ◽  
Tumor Staging ◽  
Public Health Issue ◽  
Screening Methods ◽  
Tissue Samples ◽  
Medical Databases ◽  
Colorectal Cancer Patients

Background: Colorectal Cancer (CRC) is a great public health issue and the outcomes of treatment depends on early diagnosis. Metabolomics may provide biomarkers for early diagnosis, staging, prognosis and follow-up. Methods: The authors searched for the results of the published studies existing in medical databases (PubMed) for all the changes in the main metabolic pathways (carbohydrate, lipid, aminoacid, nucleotide and other important metabolites) of the CRC patients and how the metabolic changes can be used as biomarkers, for tumor staging, prognosis and follow-up. Results: While most of the metabolites values in biological fluids or tissue samples are modified (either increased or decreased) and the results are usually constant across the studies it seems that only patterns of metabolites (fingerprints of 5, 15 or even 30 metabolites) can be used for the regarding issues mentioned above. Conclusion: Some studies conclude that some metabolomic models are statistically much better than current existing markers and may become screening methods in the near future.

Soluble CD44 and CD44v6 serum levels in patients with colorectal cancer are independent of tumor stage and tissue expression of CD44v6

1998 ◽  
Vol 93 (5) ◽  
pp. 790-794 ◽  
Author(s):  
S. Weg-Remers ◽  
U. Hildebrandt ◽  
G. Feifel ◽  
C. Moser ◽  
M. Zeitz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Serum Levels ◽  
Tumor Stage ◽  
Tissue Expression ◽  
Soluble Cd44

Multifactorial prospective study of tumoral factors related to disease-free survival (DFS) in colorectal cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3604-3604
Author(s):  
G. Milano ◽  
M. Francoual ◽  
A. Bourgeon ◽  
D. Benchimol ◽  
M. Chazal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Methylenetetrahydrofolate Reductase ◽  
Tumor Staging ◽  
Dihydropyrimidine Dehydrogenase ◽  
Tumor Resection ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
Proximal Colon ◽  
Intron 1 ◽  
Cox Analysis

3604 Background: There is still a need to identify faithful biological prognostic factors in colorectal cancer, particularly in stage 2, so as to decide upon adjuvant treatment. We thus conducted a prospective multicentric multifactorial study to this end. Methods: Primary colorectal tumors (30 stage 1, 119 stage 2, 107 stage 3) were prospectively collected in 256 patients undergoing total tumor resection (152 men, 104 women ; mean age 69, extremes 29–90). Adjuvant 5FU-based chemotherapy was administered in 92 patients. Median follow-up was 54 months (53 patients developed metastasis or recurrence). Tumors were analyzed for thymidylate synthase (TS), thymidine phosphorylase and dihydropyrimidine dehydrogenase expression (RT-PCR), TS activity (radioenzymatic assay), EGFR level (ligand-binding assay), VEGF (Elisa), DNA content and cell cycle (flow cytometry), p53 mutations (exon 4 to 8), microsatellite instability (bat 25, bat 26), EGFR genotype (CA repeats in intron 1 and -216G>T), TS genotype in 3’ (6 bp deletion) and 5’ (28 bp repeats including the G>C mutation), and methylenetetrahydrofolate reductase genotype (677C>T and 1298A>C). Results: With the exception of tumor TS expression (p = 0.034, the higher the expression, the better the DFS), none of the analyzed parameters were linked to DFS. In multivariate Cox analysis, tumor staging (p = 0.001) and TS expression (p = 0.062) were the sole factors associated to DFS. Focus on tumoral EGFR revealed large inter-patient variability (from 1 to 510 fmol/mg prot) with a significant influence of tumor localisation (p = 0.009, higher in proximal colon) and differentiation status (p = 0.01, higher in poorly differentiated tumors). EGFR within the tumors was 30 % lower than in adjacent normal mucosa (p<0.001). The longer the intron 1 CA repeats, the higher the tumor EGFR (p = 0.044). EGFR -216G>T polymorphism was linked to intron 1 polymorphism, although -216G>T did not influence EGFR levels. Conclusions: The present results underline the major impact of TS expression as a prognostic factor and provide new insights in the knowledge of EGFR in colorectal cancer. No significant financial relationships to disclose.

scholarly journals Microbiota metabolic exchange is critical for colorectal cancer redox homeostasis and growth

2020 ◽  
Author(s):  
Hannah Bell ◽  
Joshua Goyert ◽  
Samuel A. Kerk ◽  
Nupur K. Das ◽  
Costas A. Lyssiotis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lactobacillus Reuteri ◽  
Redox Homeostasis ◽  
Critical Role ◽  
Redox Balance ◽  
Tumor Stage ◽  
Response To Therapy ◽  
Cysteine Oxidation ◽  
Inflammatory Microenvironment ◽  
Metabolic Exchange

AbstractIntestinal microbiota play a fundamental role in human health and disease. Microbial dysbiosis is a hallmark of colorectal cancer (CRC) as tumor stage-specific shifts potentiate tumor growth, influence the inflammatory microenvironment, and alter response to therapy. Recent work has demonstrated a critical role for microbial metabolite exchange in host response. However, the role of most microbial metabolites in colon cancer growth is unclear. To better understand how metabolic exchange between the microbiota and tumor epithelium alter CRC growth, a screen of the most abundant bacterially derived metabolites was assessed. Several metabolites were found to alter CRC growth, but reuterin most significantly suppressed CRC cell proliferation. Reuterin is a bifunctional metabolite containing both hydroxy and aldehyde functional groups. Reuterin is primarily synthesized from glycerol by Lactobacillus reuteri, a commensal bacterium found throughout the gastrointestinal tract. We found that reuterin suppresses growth via alterations to the redox balance of CRC cells. Mechanistically, reuterin potentiates reactive oxygen species (ROS) which leads to irreversible cysteine oxidation and enhanced cell death. Supplementation of either antioxidants or hydrogen sulfide fully rescued growth, suggesting that reuterin is suppressing CRC growth through protein oxidation. These studies demonstrate the potential of reuterin to act as a potent chemotherapeutic for treating colorectal cancers.

scholarly journals Serum Level and Tumor Tissue Expression of Ribonucleotide-Diphosphate Reductase Subunit M2 B: A Potential Biomarker for Colorectal Cancer

2021 ◽  
Author(s):  
Naser Mobarra ◽  
Hanieh Gholamalizadeh ◽  
Kaed A. Abdulhussein ◽  
Fatemeh Taheri Asl ◽  
Mobina Sadat Mirvahabi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Serum Level ◽  
Tumor Metastasis ◽  
Tumor Tissue ◽  
Tumor Staging ◽  
Tissue Expression ◽  
Control Group ◽  
Potential Biomarker ◽  
The Mean ◽  
First Time

Abstract Background: This study aimed to investigate whether serum level and tissue expression of Ribonucleotide-diphosphate Reductase subunit M2 B (RRM2B) could be recognized as reliable biomarkers for colorectal cancer (CRC) progression and metastasis.Methods and Results: This descriptive-analytic cohort study was conducted on 50 newly diagnosed CRC patients (stage II, III) and 50 healthy individuals. The new cases had not received any therapeutic intervention and underwent surgery immediately after the initial diagnosis. Tumorous tissues and marginal healthy tissues as control were excised to determine the mRNA tissue expression of RRM2B by Real-Time PCR. Serum RRM2B protein was measured using an ELISA method once in the control group and in the patients before, one, and three months after surgery. The tumor metastasis node (TMN) classification system and liver metastasis were evaluated in CRC patients. The mean RRM2B gene expression in tumor tissue was 51% lower than adjacent normal tissue (P < 0.001). We did not find a significant relationship between serum level of RRM2B and tumor staging and metastasis in patients before surgery (P = 0.373, P = 0.189), one month after surgery (P = 0.960, P = 0.088), and three months after surgery (P = 0.407, P = 0.724). RRM2B expression in tumor tissue was not associated with tumor staging and metastasis (P = 0.254, P = 0.721)Conclusion: Our study indicates the first time evidence that RRM2B may serve as a potential biomarker for CRC.

scholarly journals HMGA2 rs968697 T>C Polymorphism is Associated With The Risk of Colorectal Cancer

2021 ◽  
Author(s):  
Zhidan Li ◽  
Jiaojiao Yang ◽  
Shulong Zhang ◽  
Xiaoting Wang ◽  
Xueren Gao
Keyword(s):  
Colorectal Cancer ◽  
In Silico Analysis ◽  
Tumor Stage ◽  
Tissue Expression ◽  
Healthy Individuals ◽  
Quantitative Real Time Pcr ◽  
Pcr Technology ◽  
And Gender ◽  
Running Head ◽  
Silico Analysis

Abstract Background: Recently, a genetic polymorphism (rs968697 T>C) in HMGA2 gene has been reported to be associated with hepatoblastoma risk. However, no studies reported the effect of the polymorphism on the risk of colorectal cancer (CRC). The study aimed to explore whether rs968697 polymorphism had a significant impact on CRC risk. Methods: A total of 500 CRC patients and 500 age and gender matched healthy individuals were genotyped by Sanger sequencing. Quantitative real-time PCR technology was used to detect the relative expression of HMGA2 gene in 30 pairs of primary CRC and adjacent non-cancerous tissues.Results: HMGA2 rs968697 polymorphism was significantly associated with CRC risk (CC vs. TT: OR=0.20, 95%CI=0.06-0.70, P=0.01; (CC+CT) vs. TT: OR=0.71, 95%CI=0.53-0.96, P=0.02; CC vs. (CT+TT): OR=0.21, 95%CI=0.06-0.73, P=0.01; C vs. T: OR=0.67, 95%CI=0.51-0.89, P<0.01). The analysis based on tumor stage indicated that HMGA2 rs968697 polymorphism was significantly associated with CRC tumor stage. In addition, the genotype-tissue expression showed that the rs968697 polymorphism was related to HMGA2 gene expression. The in silico analysis showed that rs968697 polymorphism located in the promoter region of HMGA2 gene could affect the binding of transcription factors. Conclusion: Our study suggested that HMGA2 rs968697 polymorphism was associated with CRC risk and might serve as a reliable biomarker to detect CRC risk. Running head: HMGA2 rs968697 T>C polymorphism and colorectal cancer

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