Impact of diabetes on clinicopathologic and genetic features of colorectal cancer formation.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 426-426
Author(s):  
Hui-li Wong ◽  
Robert N. Jorissen ◽  
Oliver Sieber ◽  
Lara Rachel Lipton ◽  
Jayesh Desai ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Propensity Scores ◽  
Cpg Island ◽  
Economic Status ◽  
Multivariate Regression Analysis ◽  
Molecular Profile ◽  
Diabetic Patients ◽  
Cpg Island Methylator Phenotype ◽  
The Impact

426 Background: Diabetes mellitus is reported to increase the risk of colorectal cancer (CRC) development and has been associated with poor tumour-specific outcomes. Here we assessed the impact of diabetes on the clinicopathologic features and tumour mutation profiles of CRC. Methods: Analysis of a prospective series of patients diagnosed with CRC between January 2000 and December 2010. Fresh-frozen and formalin-fixed, paraffin-embedded tumour specimens were retrieved and genomic DNA extracted for analysis of microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and mutations in BRAF, KRAS, PIK3CA, TP53 and APC genes. Propensity-score matching and logistic regression were used to estimate the association of diabetes with tumour molecular profile, controlling for age, sex, tumour stage, body mass index (BMI), smoking and socio-economic status. Results: Of the 1,348 patients assessed, 288 (21.4%) had a history of diabetes mellitus. Compared to patients without diabetes, diabetics were more likely to be older (age > 70 yrs: 56% vs 47%, p = 0.006), male (57% vs 47%, p = 0.002) and have a higher BMI (BMI > 25: 82% vs 65%, p < 0.0001). There were no statistically significant differences in tumour site, differentiation or lymphovascular invasion. Propensity scores were used to match 260 diabetic patients to an equal number of nondiabetics. In multivariate regression analysis, diabetes was associated with BRAF-mutated tumours (OR 2.81, 95% CI 1.16-7.59, p = 0.029) and showed a trend towards MSI-high tumours (OR 1.54, 95% CI 0.91-2.63, p = 0.110). Results are shown in the Table. Survival analysis is planned. Conclusions: CRC patients with diabetes are older, more likely male and have higher BMI than non-diabetics. In this preliminary analysis, an association between diabetes and BRAF-mutant CRC was found, and may explain reported differences in outcomes for diabetic CRC patients. [Table: see text]

scholarly journals Clinicopathological features of Egyptian colorectal cancer patients regarding somatic genetic mutations especially in KRAS gene and microsatellite instability status: a pilot study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Neemat M. Kassem ◽  
Gamal Emera ◽  
Hebatallah A. Kassem ◽  
Nashwa Medhat ◽  
Basant Nagdy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Human Cancer ◽  
Statistical Significance ◽  
Public Health Problem ◽  
World Health ◽  
Cpg Island Methylator Phenotype ◽  
Number Of Patients ◽  
The Impact

Abstract Background Colorectal cancer (CRC) is the third most common cause of cancer-related deaths which contributes to a significant public health problem worldwide with 1.8 million new cases and almost 861,000 deaths in 2018 according to the World Health Organization. It exhibits 7.4% of all diagnosed cancer cases in the region of the Middle East and North Africa. Molecular changes that happen in CRCs are chromosomal instability, microsatellite instability (MSI), and CpG island methylator phenotype. The human RAS family (KRAS, NRAS, and HRAS) is the most frequently mutated oncogenes in human cancer appearing in 45% of colon cancers. Determining MSI status across CRCs offers the opportunity to identify patients who are likely to respond to targeted therapies such as anti-PD-1. Therefore, a method to efficiently determine MSI status for every cancer patient is needed. Results KRAS mutations were detected in 31.6% of CRC patients, namely in older patients (p = 0.003). Codons 12 and 13 constituted 5/6 (83.3%) and 1/6 (16.7%) of all KRAS mutations, respectively. We found three mutations G12D, G12C, and G13D which occur as a result of substitution at c.35G>A, c.34G>T, and c.38G>A and have been detected in 4/6 (66.6%), 1/6 (16.7%), and 1/6 (16.7%) patients, respectively. Eleven (57.9%) patients had microsatellite instability-high (MSI-H) CRC. A higher percentage of MSI-H CRC was detected in female patients (p = 0.048). Eight patients had both MSI-H CRC and wild KRAS mutation with no statistical significance was found between MSI status and KRAS mutation in these studied patients. Conclusion In conclusion, considering that KRAS mutations confer resistance to EGFR inhibitors, patients who have CRC with KRAS mutation could receive more tailored management by defining MSI status. MSI-high patients have enhanced responsiveness to anti-PD-1 therapies. Thus, the question arises as to whether it is worth investigating this association in the routine clinical setting or not. Further studies with a larger number of patients are needed to assess the impact of MSI status on Egyptian CRC care.

scholarly journals The Role of the CpG Island Methylator Phenotype in Colorectal Cancer Prognosis Depends on Microsatellite Instability Screening Status

2010 ◽  
Vol 16 (6) ◽  
pp. 1845-1855 ◽  
Author(s):  
Anna M. Dahlin ◽  
Richard Palmqvist ◽  
Maria L. Henriksson ◽  
Maria Jacobsson ◽  
Vincy Eklöf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Cancer Prognosis ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

scholarly journals Targeting Immune-Related Molecules in Cancer Therapy: A ComprehensiveIn VitroAnalysis on Patient-Derived Tumor Models

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Claudia Maletzki ◽  
Philine Scheinpflug ◽  
Anika Witt ◽  
Ernst Klar ◽  
Michael Linnebacher
Keyword(s):  
Cell Lines ◽  
Cpg Island ◽  
Molecular Subtype ◽  
Combined Treatment ◽  
Peripheral Blood Lymphocytes ◽  
Molecular Characteristics ◽  
Target Cells ◽  
Selective Treatment ◽  
Cpg Island Methylator Phenotype ◽  
The Impact

This study investigated the impact of immune-related pathway inhibition, among them indolamine 2,3-dioxygenase (IDO), alone and together with immune cells on growth and viability of colorectal cancer (CRC) cells. A panel of patient-derived CRC cell lines with different molecular characteristics (CpG island methylator phenotype, chromosomal, and microsatellite instability) was included. Initial phenotyping of CRC cell lines (n=17) revealed high abundance of immunosuppressive checkpoint-molecules in general, but an individual profile for IDO. Presence of immune-related molecules was independent of the molecular subtype. Selective treatment of CRC cell lines showing high or low IDO expression (n=2 cell lines each) was performed with single agents and combinations of Indoximod, Curcumin, and Gemcitabine with and without the addition of peripheral blood lymphocytes (PBL) in an allogeneic setting. All substances affected CRC cell growth in a cell line specific manner. The combination of Curcumin and Gemcitabine proved to be most effective in tumor cell elimination. Functional read-out analyses identified cellular senescence, after both single and combined treatment. Curcumin alone exerted strong cytotoxic effects by inducing early and late apoptosis. Necrosis was not detectable at all. Addition of lymphocytes generally boosted antitumoral effects of all IDO-inhibitors, with up to 80 % cytotoxicity for the Curcumin treatment. Here, no obvious differences became apparent between individual cell lines. Combined application of Curcumin and low-dose chemotherapy is a promising strategy to kill tumor target cells and to stimulate antitumoral immune responses.

scholarly journals Epithelial-Mesenchymal Transition Phenotype, Metformin, and Survival for Colorectal Cancer Patients with Diabetes Mellitus II

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yaodu Wang ◽  
Zhiyang Wu ◽  
Likuan Hu
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Disease Free Survival ◽  
Multivariate Regression Analysis ◽  
Stage I ◽  
Clinicopathological Parameters ◽  
Mesenchymal Transition ◽  
Patients With Diabetes ◽  
E Cadherin

Objectives. We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice. Methods. We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0. Results. In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin (P=0.014) and less vimentin (P=0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 (P=0.048, P=0.009), tumor invasive depth (T) (P<0.001, P=0.045), and lymph invasion (N) (P=0.013, P=0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P=0.038) and metformin use (P=0.015P=0.044) and lymph invasion (P=0.016P=0.023) were considered as the prognostic factors for both DFS and overall survival (OS). Conclusion. Our study suggested that metformin may impede the EMT process and improve survival for stage I–III CRC patients with DM II.

scholarly journals CpG Island Methylator Phenotype-Low (CIMP-Low) in Colorectal Cancer: Possible Associations with Male Sex and KRAS Mutations

2006 ◽  
Vol 8 (5) ◽  
pp. 582-588 ◽  
Author(s):  
Shuji Ogino ◽  
Takako Kawasaki ◽  
Gregory J. Kirkner ◽  
Massimo Loda ◽  
Charles S. Fuchs
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Kras Mutations ◽  
Male Sex ◽  
Methylator Phenotype

Adjuvant Supplementation with L-Carnitine in Diabetic Population and its effects on Lipid Parameters

2021 ◽  
Vol 15 (8) ◽  
pp. 2017-2019
Author(s):  
Rao Salman Aziz ◽  
Usman Saeed ◽  
Nasim Aslam Ghumman ◽  
Muhammad Arshad ◽  
Asif Sohail ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Triglyceride Level ◽  
Clinical Care ◽  
Diabetic Patients ◽  
Healthy Population ◽  
Patients With Diabetes ◽  
Diabetic Population ◽  
Large Discount ◽  
The Impact ◽  
Lipid Parameters

Background: Diabetes is a complicated disease requires continuous clinical care, to govern blood sugar. Aim: To decides the impact of management of L carentin to diabetics at the lipid profile. Methods: This study turned into performed on 120 diabetic Patients had been decided on from endocrinology and diabetes, inside decided on standards. The Patients distributed into three Strata (1st Strata of healthy population and two Strata of patients with diabetes who were on metformin and glibenclamide, one Strata took a L carnitine in a dose of 1000 mg TDS and a Strata dealing with a placebo for a period of ninety days). Results: It is observed those who are on Lcarnitine, confirmed a large discount (p <0.05) with inside the triglyceride level, at the same time as no large adjustments had been located withinside the level of cholesterol and HDL and LDL. Conclusion: These study outcomes that management of L carentin improved profile of lipid in type-2diabetic Patients. Keyword: Dyslipidemia, Diabetes mellitus (DM), l-carnitine (LC).

scholarly journals IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype

2009 ◽  
Vol 31 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Hiromu Suzuki ◽  
Shinichi Igarashi ◽  
Masanori Nojima ◽  
Reo Maruyama ◽  
Eiichiro Yamamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Responsive Gene ◽  
Methylator Phenotype
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