A study on the genomic alterations of transformation from colorectal adenoma to colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15607-e15607
Author(s):  
Qingjian Chen ◽  
Pan Yang ◽  
Linna Luo ◽  
Wenhua Fan ◽  
Chen Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tissue Sample ◽  
Intraepithelial Neoplasia ◽  
Stage I ◽  
Tissue Samples ◽  
Diagnostic Potential ◽  
Notch Pathways ◽  
Colorectal Cancer Patients ◽  
Villous Adenomas

e15607 Background: Colorectal cancer is one of the most common malignancies worldwide. Approximately 85% of colorectal cancers are thought to result from adenoma. However, the molecular mechanism of adenoma transformation into colorectal cancer is still unclear. Methods: Ninety-nine adenoma patients aged from 25 to 78 years old were enrolled in this study. We collected tissue sample from each patient and 77 matched blood samples. Pathological subtypes included tubular villous adenomas, villous adenomas, tubular adenomas, high-grade intraepithelial neoplasia, and polyps. Eighty-one stage I colorectal cancer patients (CRC I) were also enrolled in this study. All samples underwent Next-generation sequencing with a panel of 405 cancer related genes. Results: Mutational profiles of adenoma and CRC I patients were compared. The top 5 most frequently mutated genes in adenoma were APC (71%), KRAS (41%), ATM (33%), RIF1 (31%), SYNE1 (28%). While in CRC I patients, top 5 mutated genes were APC (78%), TP53 (57%), TTN (35%), KRAS (33%) and TCF7L2 (22%). There were significant differences between TP53 and TTN by chi-square test. The frequency, number and TMB of mutations in stage I colorectal cancer patients were significantly higher than those in various adenoma subtypes. Stage I colorectal cancer patients have more mutated genes enriched in the Wnt and Notch pathways than adenoma patients. We analyzed mutation signatures in CRC I and adenoma patients, and CRC I were more focused on mutation signatures of mismatch repair such as signature 1, signature 6, signature 10, and signature 15. A total of 391 mutations were identified in tissue samples, while 130 mutations were found in plasma cell-free DNA, with 116 mutations shared between them. The two genes with the highest consistency between tissue and blood were PAX7 and KMT2D. Conclusions: TP53 and TTN are associated with the transition from CRC I to adenoma, and Wnt and Notch pathways may also be involved. PAX7 and KMT2D mutations frequently found in adenoma tissue and blood cfDNA demonstrate the diagnostic potential of these two genes in clinic.

scholarly journals Optimal Follow-up of Stage I Colorectal Cancer Patients

2006 ◽  
Vol 59 (10) ◽  
pp. 857-862 ◽  
Author(s):  
T. Higuchi ◽  
M. Enomoto ◽  
K. Sugihara
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Stage I ◽  
Colorectal Cancer Patients

Blood-based screening for methylation changes in colorectal cancer patients using novel nanotechnologies.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 384-384
Author(s):  
Nita Ahuja ◽  
Ruby Kwak ◽  
Brian Keeley ◽  
Alejandro Stark ◽  
Angela Anna Guzzetta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Screening ◽  
Cancer Patients ◽  
Methylation Status ◽  
High Sensitivity ◽  
Single Copy ◽  
Tissue Samples ◽  
Methylation Frequency ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues

384 Background: Identification of blood-based biomarkers for cancer screening is essential in order to develop novel and minimally invasive methods for colorectal cancer screening. Our lab has successfully applied a novel nanotechnology that allows us to detect and amplify a single tumor DNA fragment in a plasma sample. This DNA is tested for methylation of several genes including TFPI2 which has shown to be highly sensitive and specific for the detection colorectal cancer in stool. Methods: Whole blood was obtained from 18 colorectal cancer patients and plasma was isolated. Plasma was processed using Methylation On Beads nanotechnology (MOB) and bisulfate treated. Methylation status was determined via quantitative PCR method. Results: Two genes, TFPI2 and IGFBP3, were detected with a high sensitivity. TFPI2, demonstrated a methylation frequency of 94.4%, which is concordant with the TFPI2 methylation frequency of 99% in primary colorectal cancer tissues. IGFBP3 showed the methylation frequency of 61.1%, which corresponds with the methylation frequency of 52% in retrospective colorectal cancer tissues in previous studies. Quantification using standard curves indicated a single copy level of DNA found in plasma. Conclusions: Blood-based screening is challenging due to extremely low quantities of circulating DNA in blood. Utilizing a novel nanotechnology that detects DNA at a single copy level, the methylation changes in colorectal cancer were successfully detected in plasmas at similar frequencies as in tissue samples. This study has demonstrated the feasablility and applicability to blood-based screening. Future studies will focus on improving the sensitivity and determining the specificity of this method.

Prognostication based on TNM staging for socioeconomically disadvantaged colorectal cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19036-e19036
Author(s):  
Yan Lu ◽  
Aaron Gehr ◽  
Jolonda Bullock ◽  
Bassam Ghabach ◽  
Latha Sri Neerukonda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Stage Iv ◽  
Safety Net ◽  
Stage I ◽  
Socioeconomically Disadvantaged ◽  
Pathologic Stage ◽  
Eligible Population ◽  
Prognostic Groups ◽  
Colorectal Cancer Patients

e19036 Background: The TNM classification system is the global standard for staging solid tumors, but the ability of TNM to differentiate prognostic groups may vary between settings because of differences in case-mix and treatments. Little information is available about prognostication using TNM in safety-net health systems, which provide care for socioeconomically disadvantaged individuals and have limited resources. Therefore, we aimed to assess the ability of TNM to differentiate prognostic groups for colorectal cancer patients in an urban safety-net cancer center. Methods: We used institutional registry data from the JPS Oncology and Infusion Center (Fort Worth, TX), which is a Comprehensive Community Cancer Program. Our eligible population included adults who were diagnosed with first primary colorectal cancer between 2008 and 2017, had TNM pathologic stage I – IV, and received at least part of the first course treatment at JPS. Our outcome of interest was 5-year all-cause mortality and our exposure of interest was TNM pathologic stage. Patients were followed from cancer diagnosis until death, loss to follow up, or end of study (December 31, 2018), whichever occurred first. We used a pseudo-observation approach and generalized linear models with log link to estimate risk ratios (RR) and corresponding 95% confidence limits (CL) comparing 5-year mortality between TNM stages, where stage I was the reference category. Results: Our eligible population comprised 655 colorectal cancer survivors, of whom 85% were aged < 65 years, 54% were male, 60% were racial/ethnic minorities, and 65% were uninsured at time of diagnosis. Stage IV patients had 4.4 times higher risk of 5-year mortality compared with stage I (RR = 4.4, 95% CL: 2.9, 6.6). Stage III patients had 2.1 times higher risk of 5-year mortality compared with stage I (RR = 2.1, 95% CL: 1.3, 3.2). Stage II patients had 1.4 times higher risk of 5-year mortality compared with stage I (RR = 1.4, 95% CL: 0.81, 2.3). Conclusions: Our findings suggest that TNM stages do not adequately differentiate colorectal cancer prognostic groups in a socioeconomically disadvantaged population. Stage IV is distinct, but stages I – III have limited differentiation and notable overlap. The use of TNM stages for colorectal cancer prognostication may be misleading for socioeconomically disadvantaged individuals. Factors beyond TNM should be considered for better prognostication in this population.

scholarly journals Disease-specific mortality among stage I–III colorectal cancer patients with diabetes: a large population-based analysis

Diabetologia ◽  
2012 ◽  
Vol 55 (8) ◽  
pp. 2163-2172 ◽  
Author(s):  
L. V. van de Poll-Franse ◽  
H. R. Haak ◽  
J. W. W. Coebergh ◽  
M. L. G. Janssen-Heijnen ◽  
V. E. P. P. Lemmens
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Large Population ◽  
Population Based ◽  
Stage I ◽  
Specific Mortality ◽  
Patients With Diabetes ◽  
Disease Specific Mortality ◽  
Colorectal Cancer Patients ◽  
Disease Specific

PERINEURAL INVASION PREDICTS POOR PROGNOSIS IN STAGE I-III COLORECTAL CANCER PATIENTS

2020 ◽  
Author(s):  
MS Lalosevic ◽  
Z Krivokapic ◽  
M Micev ◽  
M Stojkovic ◽  
S Dragasevic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Perineural Invasion ◽  
Stage I ◽  
Colorectal Cancer Patients

Immunobead multiplex RT-PCR detection of carcinoembryonic genes expressing cells in the blood of colorectal cancer patients

2005 ◽  
Vol 43 (2) ◽  
Author(s):  
Richard Douard ◽  
Stéphane Moutereau ◽  
Valérie Serru ◽  
Jean Patrick Sales ◽  
Philippe Wind ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Stage I ◽  
Stage Iii ◽  
Cell Detection ◽  
Circulating Tumour Cells ◽  
Healthy Individuals ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Colorectal Cancer Patients

AbstractCirculating cell detection using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques has been studied as a new prognostic factor in colorectal cancer patients. With the view of enhancing detection sensitivity, we developed a new multiplex RT-PCR assay for circulating cell detection based on the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5; formerly CEA) and CEACAM7 (formerly CGM2).Between November 2002 and December 2003, 45 stage III-IV, 39 stage I-II colorectal cancer patients, 32 non-colorectal cancer patients and 41 healthy individuals were included. Positive selection using HEA-125 immunobeads was applied to blood samples before mRNA extraction, cDNA synthesis and a multiplex CEACAM5/CEACAM7 RT-PCR assay. For both CEACAM5 and CEACAM7, the limit of detection was found to be as low as 1 expressing cell in 10The multiplex RT-PCR assay was negative for the 41 healthy individuals and the 32 non-colorectal cancer patients. The test was positive in 53/84 (63%) of the colorectal cancer patients for CEACAM5 and/or CEACAM7, whereas 32/84 (38%) were positive for both markers. Colorectal cancer patients were positive for one of the two markers in 80% of cases (36/45) for stage III-IV patients (CEACAM5 73%, CEACAM7 51%) and in 44% of cases (17/39) for stage I-II patients.This multiplex RT-PCR assay with two markers proved to be more sensitive than use of a single marker in detecting circulating tumour cells. The discrepant expression of CEACAM5 and CEACAM7 may label circulating tumour cells that have different levels of differentiation and subsequent aggressive behaviour.

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