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Different lipid metabolic profiles and their associated genes in sessile serrated adenoma or polyps compared to hyperplastic polyps.

ABSTRACT: The serrated pathway is important in the development of colorectal cancer; currently, knowledge about the lipid metabolism profiles of serrated lesions is limited. Clinical characteristics were compared via Pearson's chi-squared test, nonparametric Kruskal-Wallis test and ANOVA. For some missing values, the MCAR test and multiple imputations were performed. Compared to patients with HP, the rates of younger patients (<50) and male patients with SSA or SSP were increased (P<0.05). Additionally, the BMI index and triglyceride levels were increased in patients with SSA or SSP. Inversely, patients with SSA/P had lower levels of HDL (P<0.05). Interestingly, the value of uric acid and tumor size in SSA/P patients tended to be greater than those in HP patients, and the ratio of patients who smoked was also increased. Other characteristics, such as LDL, ALB, γ-GT, and the N/L ratio, were similar among the subtypes of serrated lesions. Analysis of GEO data (GSE43841) showed that 9 genes were associated with lipid metabolism, including ADRB3, DEGS2, PRKACB, SLC44A1, and CA4. PRKACB was downregulated in SSA/P tissue compared to HP tissue samples from the GSE76987 dataset and our hospital. In conclusion, compared to benign HP, lower HDL levels and higher triglyceride levels tended to occur in CRC precursor SSA/P lesions, and these factors may be associated with metabolic genomic markers, such as PRKACB.

SUBMITTER: Tang C

PROVIDER: S-EPMC9185600 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Different lipid metabolic profiles and their associated genes in sessile serrated adenoma or polyps compared to hyperplastic polyps.

Tang Chaotao C Li Jun J Yang Zhenzhen Z Chen Youxiang Y Zeng Chunyan C

American journal of cancer research 20220515 5

The serrated pathway is important in the development of colorectal cancer; currently, knowledge about the lipid metabolism profiles of serrated lesions is limited. Clinical characteristics were compared via Pearson's chi-squared test, nonparametric Kruskal-Wallis test and ANOVA. For some missing values, the MCAR test and multiple imputations were performed. Compared to patients with HP, the rates of younger patients (<50) and male patients with SSA or SSP were increased (P<0.05). Additionally, t ...[more]

PMID: 35693083

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Project description:BackgroundSessile serrated adenomas/polyps are distinguished from hyperplastic colonic polyps subjectively by their endoscopic appearance and histological morphology. However, hyperplastic and sessile serrated polyps can have overlapping morphological features resulting in sessile serrated polyps diagnosed as hyperplastic. While sessile serrated polyps can progress into colon cancer, hyperplastic polyps have virtually no risk for colon cancer. Objective measures, differentiating these types of polyps would improve cancer prevention and treatment outcome.MethodsRNA-seq training data set and Affimetrix, Illumina testing data sets were obtained from Gene Expression Omnibus (GEO). RNA-seq single-end reads were filtered with FastX toolkit. Read mapping to the human genome, gene abundance estimation, and differential expression analysis were performed with Tophat-Cufflinks pipeline. Background correction, normalization, and probe summarization steps for Affimetrix arrays were performed using the robust multi-array method (RMA). For Illumina arrays, log2-scale expression data was obtained from GEO. Pathway analysis was implemented using Bioconductor package GSAR. To build a platform-independent molecular classifier that accurately differentiates sessile serrated and hyperplastic polyps we developed a new feature selection step. We also developed a simple procedure to classify new samples as either sessile serrated or hyperplastic with a class probability assigned to the decision, estimated using Cantelli's inequality.ResultsThe classifier trained on RNA-seq data and tested on two independent microarray data sets resulted in zero and three errors. The classifier was further tested using quantitative real-time PCR expression levels of 45 blinded independent formalin-fixed paraffin-embedded specimens and was highly accurate. Pathway analyses have shown that sessile serrated polyps are distinguished from hyperplastic polyps and normal controls by: up-regulation of pathways implicated in proliferation, inflammation, cell-cell adhesion and down-regulation of serine threonine kinase signaling pathway; differential co-expression of pathways regulating cell division, protein trafficking and kinase activities.ConclusionsMost of the differentially expressed pathways are known as hallmarks of cancer and likely to explain why sessile serrated polyps are more prone to neoplastic transformation than hyperplastic. The new molecular classifier includes 13 genes and may facilitate objective differentiation between two polyps.

Dataset Information

Different lipid metabolic profiles and their associated genes in sessile serrated adenoma or polyps compared to hyperplastic polyps.

Publications

Different lipid metabolic profiles and their associated genes in sessile serrated adenoma or polyps compared to hyperplastic polyps.

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