In-depth proteomic delineation of the colorectal cancer exoproteome: Mechanistic insight and identification of potential biomarkers

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.

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Genome-Wide Open Chromatin Methylome Profiles in Colorectal Cancer

Biomolecules ◽

10.3390/biom10050719 ◽

2020 ◽

Vol 10 (5) ◽

pp. 719

Author(s):

Muhiddin Ishak ◽

Rashidah Baharudin ◽

Isa Mohamed Rose ◽

Ismail Sagap ◽

Luqman Mazlan ◽

...

Keyword(s):

Colorectal Cancer ◽

Clustering Analysis ◽

Operating Characteristic ◽

Differential Methylation ◽

Chromosome 1 ◽

Open Chromatin ◽

Genome Wide ◽

Top 40 ◽

Cancer Tissues ◽

Potential Biomarkers

The methylome of open chromatins was investigated in colorectal cancer (CRC) to explore cancer-specific methylation and potential biomarkers. Epigenome-wide methylome of open chromatins was studied in colorectal cancer tissues using the Infinium DNA MethylationEPIC assay. Differentially methylated regions were identified using the ChAMP Bioconductor. Our stringent analysis led to the discovery of 2187 significant differentially methylated open chromatins in CRCs. More hypomethylated probes were observed and the trend was similar across all chromosomes. The majority of hyper- and hypomethylated probes in open chromatin were in chromosome 1. Our unsupervised hierarchical clustering analysis showed that 40 significant differentially methylated open chromatins were able to segregate CRC from normal colonic tissues. Receiver operating characteristic analyses from the top 40 probes revealed several significant, highly discriminative, specific and sensitive probes such as OPLAH cg26256223, EYA4 cg01328892, and CCNA1 cg11513637, among others. OPLAH cg26256223 hypermethylation is associated with reduced gene expression in the CRC. This study reports many open chromatin loci with novel differential methylation statuses, some of which with the potential as candidate markers for diagnostic purposes.

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Novel Biomarker Candidates for Colorectal Cancer Metastasis: A Meta-analysis of In Vitro Studies

Cancer Informatics ◽

10.4137/cin.s40301 ◽

2016 ◽

Vol 15s4 ◽

pp. CIN.S40301

Author(s):

Nguyen Phuoc Long ◽

Wun Jun Lee ◽

Nguyen Truong Huy ◽

Seul Ji Lee ◽

Jeong Hill Park ◽

...

Keyword(s):

Colorectal Cancer ◽

Microarray Data ◽

Cancer Metastasis ◽

Meta Analysis ◽

Data Sets ◽

Proteomic Data ◽

Colorectal Cancer Metastasis ◽

Microarray Studies ◽

Potential Biomarkers

Colorectal cancer (CRC) is one of the most common and lethal cancers. Although numerous studies have evaluated potential biomarkers for early diagnosis, current biomarkers have failed to reach an acceptable level of accuracy for distant metastasis. In this paper, we performed a gene set meta-analysis of in vitro microarray studies and combined the results from this study with previously published proteomic data to validate and suggest prognostic candidates for CRC metastasis. Two microarray data sets included found 21 significant genes. Of these significant genes, ALDOA, IL8 (CXCL8), and PARP4 had strong potential as prognostic candidates. LAMB2, MCM7, CXCL23A, SERPINA3, ABCA3, ALDH3A2, and POLR2I also have potential. Other candidates were more controversial, possibly because of the biologic heterogeneity of tumor cells, which is a major obstacle to predicting metastasis. In conclusion, we demonstrated a meta-analysis approach and successfully suggested ten biomarker candidates for future investigation.

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Three CircRNAs Function as Potential Biomarkers for Colorectal Cancer

Clinical Laboratory ◽

10.7754/clin.lab.2020.191265 ◽

2020 ◽

Vol 66 (12/2020) ◽

Author(s):

Jinling Zhang ◽

Ang Cai ◽

Yu Zhao

Keyword(s):

Colorectal Cancer ◽

Potential Biomarkers

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miR128 and LET-7 microRNAs as potential biomarkers for selection of patients with metastatic colorectal cancer candidate to cetuximab/panitumumab therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.3636 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 3636-3636 ◽

Cited By ~ 3

Author(s):

L. Landi ◽

F. Biagioni ◽

V. Ludovini ◽

A. Sacconi ◽

A. Destro ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Selection Of Patients ◽

Selection Of ◽

Potential Biomarkers

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APC and TP53 as potential biomarkers for EGFR sensitivity in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4094 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4094-4094

Author(s):

Ramya Thota ◽

Mingli Yang ◽

Thomas Davis ◽

Michael J. Schell ◽

Warren Jack Pledger ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Targeted Therapies ◽

Predictive Value ◽

Molecular Subtypes ◽

Gene Expression Signature ◽

Wild Type ◽

Potential Response ◽

Mutation Status ◽

Potential Biomarkers

4094 Background: The Consensus Molecular Subtypes (CMS) of colorectal cancer (CRC) have prognostic and predictive value in identifying patients that derive benefit from EGFR targeted therapies. The CMS2 cohort was specifically noted to predict response to cetuximab. Besides CMS classification, we recently reported a two-gene mutation signature of APC and TP53 (AP) that predicts potential response to cetuximab. In this study, we hypothesize AP mutations, in addition to CMS cohorts, predict cetuximab sensitivity. Methods: A prespecified and validated 203 gene expression signature score measuring cetuximab sensitivity (CTX S-score) was used as a surrogate for response to cetuximab sensitivity. A cohort of 458 patients with colorectal cancer was accrued between October 2006 and September 2011. The population classified into CMS cohorts, and CTX-S scores were determined across each of the cohorts based on AP mutation status. Results: Among 458 tumor samples sequenced, AP mutations were identified as significantly associated with higher CTX-S scores. Among the CMS 1-4 cohorts identified, AP mutations were noted in 13 of 77 (17%) patients in CMS1 cohort, 87 of 116 (75%) patients in CMS2 cohort, 15 of 64 (23%) patients in CMS3 cohort, 46 of 112 (41%) patients in CMS4 cohort, indicating that AP mutations are dominant in CMS2 cohort. Further CTX-S score comparisons across CMS cohorts based on AP status show that AP mutated tumors have higher CTX-S scores than non-AP mutated tumors—irrespective of the CMS cohorts (p<0.05 unpaired, two-tailed t tests). Conclusions: In our study, we noted CMS2 cohort has high predicted sensitivity to cetuximab. Across other CMS cohorts, AP mutations were associated with higher CTX-S scores compared to those with AP wild-type tumors, suggesting both CMS2 and AP mutations contribute to CTX sensitivity.

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Potential biomarkers for anti-EGFR therapy in metastatic colorectal cancer

Tumor Biology ◽

10.1007/s13277-016-5140-9 ◽

2016 ◽

Vol 37 (9) ◽

pp. 11645-11655 ◽

Cited By ~ 14

Author(s):

Jiao Yang ◽

Shuting Li ◽

Biyuan Wang ◽

Yinying Wu ◽

Zheling Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Potential Biomarkers

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Molecular Characterization of Advanced Colorectal Cancer Using Serum Proteomics and Metabolomics

10.21203/rs.3.rs-138800/v1 ◽

2021 ◽

Author(s):

Jun Rao ◽

Xianghui Wan ◽

Fangfang Tou ◽

Qinsi He ◽

Aihua Xiong ◽

...

Keyword(s):

Colorectal Cancer ◽

Molecular Characterization ◽

Arachidonic Acid Metabolism ◽

Health Concern ◽

Glutathione Metabolism ◽

Serum Samples ◽

Serum Proteomics ◽

Potential Biomarkers ◽

Tof Ms

Abstract Introduction Colorectal cancer (CRC) is a growing public health concern with high mortality rate. However, there are no valid diagnostic biomarkers and few therapeutic strategies available for CRC, especially advanced CRC, since the pathogenic mechanisms remain poorly understood. Objective To comprehensively reveal molecular characterization of advanced CRC, we applied integrated proteomic and metabolomic analyses on serum samples from 20 patients with CRC at stage III or IV. Methods In the present study, we took advantage of nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies. Results Overall, 551 proteins and 719 metabolites were identified in those serum samples, respectively. Hierarchical clustering analysis indicated much more remarkable diversity in proteomic profiles than metabolomic profiles. Further functional analysis suggested that ten key pathways associated with cancer cell metabolism were dissected including glycolysis/gluconeogenesis, biosynthesis of amino acids, glutathione metabolism, and arachidonic acid metabolism, based on which protein-protein interaction network analysis was thus constructed with 80 proteins and 21 metabolites. Moreover, the regulatory network in advanced CRC was established according to correlation analysis, indicating conserved roles of metabolome and lipids & lipid like molecules in human serum. Nevertheless, three metabolites and two proteins including hydroquinone, leucenol and sphingomyelin were supposed to be potential biomarkers, which were determined to be positively and significantly correlated with CEA and/or CA 19-9.Conclusions Altogether, our work not only extended our understanding on the physiopathology of advanced CRC, but provided potential biomarkers to improve the accuracy of the diagnosis and monitoring of the syndrome.

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