Dataset Information

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

ABSTRACT:

Background

A major roadblock to reducing the mortality of colorectal cancer (CRC) is prompt detection and treatment, and a simple blood test is likely to have higher compliance than all of the current methods. The purpose of this report is to examine the utility of a mass spectrometry-based blood serum protein biomarker test for detection of CRC.

Materials and methods

Blood was drawn from individuals (n = 213) before colonoscopy or from patients with nonmetastatic CRC (n = 50) before surgery. Proteins were isolated from the serum of patients using targeted liquid chromatography-tandem mass spectrometry. We designed a machine-learning statistical model to assess these proteins.

Results

When considered individually, over 70% of the selected biomarkers showed significance by Mann-Whitney testing for distinguishing cancer-bearing cases from cancer-free cases. Using machine-learning methods, peptides derived from epidermal growth factor receptor and leucine-rich alpha-2-glycoprotein 1 were consistently identified as highly predictive for detecting CRC from cancer-free cases. A five-marker panel consisting of leucine-rich alpha-2-glycoprotein 1, epidermal growth factor receptor, inter-alpha-trypsin inhibitor heavy-chain family member 4, hemopexin, and superoxide dismutase 3 performed the best with 70% specificity at over 89% sensitivity (area under the curve = 0.86) in the validation set. For distinguishing regional from localized cancers, cross-validation within the training set showed that a panel of four proteins consisting of CD44 molecule, GC-vitamin D-binding protein, C-reactive protein, and inter-alpha-trypsin inhibitor heavy-chain family member 3 yielded the highest performance (area under the curve = 0.75).

Conclusions

The minimally invasive blood biomarker panels identified here could serve as screening/detection alternatives for CRC in a human population and potentially useful for staging of existing cancer.

SUBMITTER: Ivancic MM

PROVIDER: S-EPMC6957232 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

Ivancic Melanie M MM Megna Bryant W BW Sverchkov Yuriy Y Craven Mark M Reichelderfer Mark M Pickhardt Perry J PJ Sussman Michael R MR Kennedy Gregory D GD

The Journal of surgical research 20191003

<h4>Background</h4>A major roadblock to reducing the mortality of colorectal cancer (CRC) is prompt detection and treatment, and a simple blood test is likely to have higher compliance than all of the current methods. The purpose of this report is to examine the utility of a mass spectrometry-based blood serum protein biomarker test for detection of CRC.<h4>Materials and methods</h4>Blood was drawn from individuals (n = 213) before colonoscopy or from patients with nonmetastatic CRC (n = 50) bef ...[more]

PMID: 31586890

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Project description:Currently, the majority of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) present with locally invasive and/or metastatic disease, resulting in five-year survival of less than 5%. The development of an early diagnostic test is, therefore, expected to significantly impact the patient's prognosis. In this study, we successfully evaluated the feasibility of identifying diagnostic cell free microRNAs (miRNAs) for early stage PDAC, through the analysis of urine samples. Using Affymetrix microarrays, we established a global miRNA profile of 13 PDAC, six chronic pancreatitis (CP), and seven healthy (H) urine specimens. Selected differentially expressed miRNAs were subsequently investigated using an independent technique (RT-PCR) on 101 urine samples including 46 PDAC, 29 CP and 26 H. Receiver operating characteristic (ROC) and logistic regression analyses were applied to determine the discriminatory potential of the candidate miRNA biomarkers. Three miRNAs (miR-143, miR-223, and miR-30e) were significantly over-expressed in patients with Stage I cancer when compared with age-matched healthy individuals (P=0.022, 0.035 and 0.04, respectively); miR-143, miR-223 and miR-204 were also shown to be expressed at higher levels in Stage I compared to Stages II-IV PDAC (P=0.025, 0.013 and 0.008, respectively). Furthermore, miR-223 and miR-204 were able to distinguish patients with early stage cancer from patients with CP (P=0.037 and 0.036). Among the three biomarkers, miR-143 was best able to differentiate Stage I (n=6) from healthy (n=26) with area under the curve (AUC) of 0.862 (95% CI 0.695-1.000), with sensitivity (SN) of 83.3% (95% CI 50.0-100.0), and specificity (SP) of 88.5% (95% CI 73.1-100.0). The combination of miR-143 with miR-30e was significantly better at discriminating between these two groups, achieving an AUC of 0.923 (95% CI 0.793-1.000), with SN of 83.3% (95% CI 50.0-100.0) and SP of 96.2% (95% CI 88.5-100.0). In this feasibility study, we demonstrate for the first time the utility of miRNA biomarkers for non-invasive, early detection of PDAC in urine specimens.

Dataset Information

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

Background

Materials and methods

Results

Conclusions

Publications

Noninvasive Detection of Colorectal Carcinomas Using Serum Protein Biomarkers.

Similar Datasets

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