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A Support Vector Machine Model Predicting the Risk of Duodenal Cancer in Patients with Familial Adenomatous Polyposis at the Transcript Levels.

ABSTRACT: Objective:Familial adenomatous polyposis (FAP) is one major type of inherited duodenal cancer. The estimate of duodenal cancer risk in patients with FAP is critical for selecting the optimal treatment strategy. Methods:Microarray datasets related with FAP were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes were identified by FAP vs. normal samples and FAP and duodenal cancer vs. normal samples. Furthermore, functional enrichment analyses of these differentially expressed genes were performed. A support vector machine (SVM) was performed to train and validate cancer risk prediction model. Results:A total of 196 differentially expressed genes were identified between FAP compared with normal samples. 177 similarly expressed genes were identified both in FAP and duodenal cancer, which were mainly enriched in pathways in cancer and metabolic-related pathway, indicating that these genes in patients with FAP could contribute to duodenal cancer. Among them, Cyclin D1, SDF-1, AXIN, and TCF were significantly upregulated in FAP tissues using qRT-PCR. Based on the 177 genes, an SVM model was constructed for prediction of the risk of cancer in patients with FAP. After validation, the model can accurately distinguish FAP patients with high risk from those with low risk for duodenal cancer. Conclusion:This study proposed a cancer risk prediction model based on an SVM at the transcript levels.

SUBMITTER: Liu W

PROVIDER: S-EPMC7315318 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Support Vector Machine Model Predicting the Risk of Duodenal Cancer in Patients with Familial Adenomatous Polyposis at the Transcript Levels.

Liu Weiqing W Dong Jian J Ma Shumin S Liang Lei L Yang Jun J

BioMed research international 20200616

<h4>Objective</h4>Familial adenomatous polyposis (FAP) is one major type of inherited duodenal cancer. The estimate of duodenal cancer risk in patients with FAP is critical for selecting the optimal treatment strategy.<h4>Methods</h4>Microarray datasets related with FAP were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes were identified by FAP vs. normal samples and FAP and duodenal cancer vs. normal samples. Furthermore, functional enrichment analyses ...[more]

PMID: 32626748

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Project description:ObjectivesDuodenal cancer in familial adenomatous polyposis (FAP) arises from adenomas. Differentially expressed genes (DEGs) in the duodenal adenoma-carcinoma pathway have been identified in murine FAP models, but similar data in patients with FAP are limited. Identifying such changes may have significance in understanding duodenal polyposis therapies and identifying cancer biomarkers. We performed a genome-wide transcriptional analysis to describe the duodenal adenoma-carcinoma sequence and determine changes distinguishing patients with FAP with and without duodenal cancer.MethodsTranscriptional profiling was performed with the Affymetrix Human Transcriptome Array 2.0 on duodenal biopsies from 12 FAP patients with duodenal cancer (FAP cases) and 12 FAP patients without cancer (FAP controls). DEGs were compared between cancer-normal, adenoma-normal, and cancer-adenoma in FAP cases and between adenomas from FAP cases and FAP controls. Significant results at P < 0.05 were filtered using fold change > 2.ResultsTwo hundred twenty-four DEGs were identified at an absolute fold change > 2. In adenoma-normal, downregulation of DEGs involved in metabolism of brush border proteins (LCT), lipids (APOB/A4), reactive oxygen species (GSTA2), and retinol (RBP2) was observed. In the cancer-adenoma comparison, upregulation of DEGs involved in cell invasion/migration (POSTN, SPP1) and downregulation of DEGs involved in Paneth differentiation (DEFA5/6) were observed. In the adenoma-adenoma comparison, downregulation of several DEGs (CLCA1, ADH1C, ANXA10) in FAP case adenomas was observed. DEGs with therapeutic potential include SPP1, which is involved in both cyclooxygenase and epidermal growth factor receptor pathways targeted by the sulindac/erlotinib combination for duodenal polyposis.DiscussionWe describe DEGs in the human duodenal adenoma-carcinoma sequence in FAP, which may have prognostic and therapeutic significance. Validation studies are needed to confirm these findings.

Project description:Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful.To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP.Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah.Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months.The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden.Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. [table: see text].Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes.clinicaltrials.gov Identifier: NCT 01187901.

Dataset Information

A Support Vector Machine Model Predicting the Risk of Duodenal Cancer in Patients with Familial Adenomatous Polyposis at the Transcript Levels.

Publications

A Support Vector Machine Model Predicting the Risk of Duodenal Cancer in Patients with Familial Adenomatous Polyposis at the Transcript Levels.

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