1663. Biological Factors In Paired Tumour and Plasma Samples: Relationship to Colorectal Cancer Pathology and 15-Year Survival

2018 ◽  
Vol 44 (11) ◽  
pp. 1842-1843
Author(s):  
Liz Baker ◽  
Norma Robinson ◽  
Mohamed Tabaqchali ◽  
David Leaper
2012 ◽  
Vol 48 ◽  
pp. S37-S38
Author(s):  
E.A. Baker ◽  
N. Robinson ◽  
M.A. Tabaqchali ◽  
D.J. Leaper

2019 ◽  
Author(s):  
Farideh Rigi ◽  
Aliakbar Jannatabad ◽  
Azra Izanloo ◽  
Reza Roshanravan ◽  
Hamid Reza Hashemian ◽  
...  

Abstract Background: Tumor pyruvate kinase M2 isoform (tM2-PK), which is an isoform of PK-glycolytic enzyme and appears on the surface of cancerous proliferating cells, has been used as a diagnostic biomarker for colorectal cancer (CRC). The aim of this study was to evaluate the tM2-PK measurement test for the diagnosis of CRCs and adenomatous polyps in plasma and stool samples in an Iranian population. Methods: In this prospective study, a total of 226 stool and 178 plasma samples were received from patients referred to colonoscopy units. tM2-PK enzyme was measured using two separate ScheBo-Biotech-AG ELISA kits for stool and plasma samples. Results: At the cut-off value of 4 U/ml, in tumor group, the sensitivity of fecal tM2-PK test was 100% and the specificity was 68%, and in polyp group, the sensitivity and specificity were 87% and 68%, respectively. At the cut-off value of 15 U/ml in tumor group, the sensitivity of plasma tM2-PK test was 98% and specificity was 74% and in polyp group the sensitivity and specificity were 98% and 74%, respectively. Based on our results, a cut-off range of 4.8-8 U/ml and >8 U/ml could be used to detect polyp and tumor in stool samples, respectively. Similarly, a cut-off range of 19-25 U/ml and >25 U/ml is recommended in plasma samples for polyp and tumor detection, respectively. Conclusions: This study revealed a high specificity and sensitivity of tM2-PK test for stool and plasma samples in patients with CRC and polyps suggesting it as a non-invasive assay to diagnose CRC and adenomatous polyps.


BioTechniques ◽  
2020 ◽  
Vol 69 (2) ◽  
pp. 99-107
Author(s):  
Soo Ann Yap ◽  
Agnieszka Münster-Wandowski ◽  
Anika Nonnenmacher ◽  
Ulrich Keilholz ◽  
Sandra Liebs

Extracellular vesicles (EVs) are taking their place as potential biomarkers in the field of liquid biopsy. In this study, EVs were isolated from plasma samples of 31 patients with colorectal cancer and melanoma via differential centrifugation and Droplet Digital™ PCR (Bio-Rad, CA, USA) was used to profile BRAF V600E/K, KRAS G12A/C/D/V and KRAS G13D mutations from EV-derived cDNA. The concordance rates with corresponding tissue were 54% and 44% in the colorectal cancer and melanoma cohort, respectively. Two patients displayed mutations in EVs not previously detected in tissue as evidence for emerging molecular resistance to anti-EGFR and BRAF/MEK inhibitor therapy prior to radiological evidence of tumor progression. We concluded that EV-derived nucleic acids may provide clinically relevant diagnostic information and mirror evolution of the disease.


2019 ◽  
Vol 65 (7) ◽  
pp. 916-926 ◽  
Author(s):  
Jingyi Li ◽  
Xin Zhou ◽  
Xiaomeng Liu ◽  
Jie Ren ◽  
Jilian Wang ◽  
...  

Abstract BACKGROUND Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-wide DNA hypermethylation analysis technique using circulating cell-free DNA (cfDNA) is attractive for the noninvasive early detection of CRC and discrimination between CRC and other cancer types. METHODS We applied the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, with a fully methylated molecules algorithm, to plasma samples from patients with CRC (n = 147) and controls (n = 136), as well as cancer and adjacent noncancerous tissue samples (n = 66). We also comparatively analyzed plasma samples from patients with hepatocellular carcinoma (HCC; n = 36). RESULTS Dozens of DNA hypermethylation markers including known (e.g., SEPT9 and IKZF1) and novel (e.g., EMBP1, KCNQ5, CHST11, APBB1IP, and TJP2) genes were identified for effectively detecting CRC in cfDNA. A panel of 80 markers discriminated early-stage CRC patients and controls with a clinical sensitivity of 74% and clinical specificity of 90%. Patients with early-stage CRC and HCC could be discriminated at clinical sensitivities of approximately 70% by another panel of 128 markers. CONCLUSIONS MCTA-Seq is a promising method for the noninvasive detection of CRC.


Pathology ◽  
2014 ◽  
Vol 46 ◽  
pp. S113
Author(s):  
Brian Ng ◽  
Diem Pham ◽  
Xi Jia ◽  
Elvina Wiadji ◽  
Nicole Watson ◽  
...  

2019 ◽  
Vol 20 (23) ◽  
pp. 6082 ◽  
Author(s):  
Stine Thorsen ◽  
Irina Gromova ◽  
Ib Christensen ◽  
Simon Fredriksson ◽  
Claus Andersen ◽  
...  

The burden of colorectal cancer (CRC) is considerable—approximately 1.8 million people are diagnosed each year with CRC and of these about half will succumb to the disease. In the case of CRC, there is strong evidence that an early diagnosis leads to a better prognosis, with metastatic CRC having a 5-year survival that is only slightly greater than 10% compared with up to 90% for stage I CRC. Clearly, biomarkers for the early detection of CRC would have a major clinical impact. We implemented a coherent gel-based proteomics biomarker discovery platform for the identification of clinically useful biomarkers for the early detection of CRC. Potential protein biomarkers were identified by a 2D gel-based analysis of a cohort composed of 128 CRC and site-matched normal tissue biopsies. Potential biomarkers were prioritized and assays to quantitatively measure plasma expression of the candidate biomarkers were developed. Those biomarkers that fulfilled the preset criteria for technical validity were validated in a case-control set of plasma samples, including 70 patients with CRC, adenomas, or non-cancer diseases and healthy individuals in each group. We identified 63 consistently upregulated polypeptides (factor of four-fold or more) in our proteomics analysis. We selected 10 out of these 63 upregulated polypeptides, and established assays to measure the concentration of each one of the ten biomarkers in plasma samples. Biomarker levels were analyzed in plasma samples from healthy individuals, individuals with adenomas, CRC patients, and patients with non-cancer diseases and we identified one protein, tropomyosin 3 (Tpm3) that could discriminate CRC at a significant level (p = 0.0146). Our results suggest that at least one of the identified proteins, Tpm3, could be used as a biomarker in the early detection of CRC, and further studies should provide unequivocal evidence for the real-life clinical validity and usefulness of Tpm3.


2002 ◽  
Vol 17 (4) ◽  
pp. 268-274 ◽  
Author(s):  
C. Arun ◽  
B. Swift ◽  
K.E. Porter ◽  
K.P. West ◽  
N.J.M. London ◽  
...  

Introduction Changes in liver blood flow caused by an unknown splanchnic vasoconstrictor have been noted in colorectal cancer patients with liver metastases. This prospective study was performed to assess whether plasma levels of big endothelin-1 (big ET-1) were raised in patients with colorectal cancer. Methods Plasma samples from peripheral vein of patients who underwent surgery for primary colorectal cancer (n=60) and those with known colorectal liver metastases (n=45) for a period of 15 months were taken prior to treatment and compared to age- and sex-matched controls (n=20). Plasma samples were analysed by using a single-step sandwich enzyme immunoassay. Immunohistochemistry and in situ hybridisation were also performed on tumour sections to investigate the expression of ET-1 by cancer cells. Results The median (range) plasma concentration of big ET-1 in controls was 2.1 pg/mL (1.2–13.4 pg/mL). The median (range) plasma concentration of big ET-1 in colorectal cancer patients with no overt hepatic metastases was 3.8 pg/mL (1.2–15.8 pg/mL), p=0.002, and the median (range) plasma concentration of big ET-1 in colorectal cancer patients with hepatic metastases was 5.2 pg/mL (1.7–30 pg/mL), p=0.0001; both were significantly elevated compared to the control group. A significant difference in immunostaining for big ET-1 was noted between paired normal colonic mucosa (median score-1) and tumour sections (median score-3), p=0.01. Conclusion This study has demonstrated elevated concentrations of big ET-1 in colorectal cancer patients, especially in those with hepatic metastases. Upregulation of ET activity in colorectal cancer could be inferred by the increased immunostaining of big ET-1 in cancer cells. Therefore, plasma big ET-1 levels should be evaluated as a potential tumour marker for the identification of hepatic metastases at an earlier stage.


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