Proteomic Approaches for Biomarker Discovery in Colorectal Cancer

2004 ◽  
pp. 111-131
Author(s):  
Richard J. Simpson ◽  
Donna S. Dorow
2021 ◽  
Vol 11 (6) ◽  
pp. 535
Author(s):  
Bader Almuzzaini ◽  
Jahad Alghamdi ◽  
Alhanouf Alomani ◽  
Saleh AlGhamdi ◽  
Abdullah A. Alsharm ◽  
...  

Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. Discovery of novel variants in local population provides confident targets for developing biomarkers for personalized medicine. We identified the need to generate high-quality sequencing data from local colorectal cancer patients and understand the pattern of occurrence of variants. In this report, we used archived samples from Saudi Arabia and used the AmpliSeq comprehensive cancer panel to identify novel somatic variants. We report a comprehensive analysis of next-generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity, and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in the large intestine. APC, RET, and EGFR genes were most frequently mutated. A higher number of variants were identified in the left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.


Oncotarget ◽  
2017 ◽  
Vol 8 (21) ◽  
pp. 35460-35472 ◽  
Author(s):  
Fan Zhang ◽  
Yuanyuan Zhang ◽  
Weiwei Zhao ◽  
Kui Deng ◽  
Zhuozhong Wang ◽  
...  

2009 ◽  
Vol 136 (5) ◽  
pp. A-749
Author(s):  
Sarah A. Goodbrand ◽  
Douglas Lamont ◽  
Michael A. Ferguson ◽  
Robert J. Steele

Author(s):  
Paula Álvarez-Chaver ◽  
Loretta De Chiara ◽  
Vicenta Soledad Martínez-Zorzano

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.


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