METHODS: We conducted transcriptome profiling on 32 colonic biopsies [11 long-duration UC, ≥20 years; and 21 short-duration UC, ≤5 years] using Affymetrix Human Transcriptome Array 2.0. Differentially expressed genes [fold change > 1.5, p < 0.05] and alternative splicing events [splicing index > 1.5, p < 0.05] were determined using the Transcriptome Analysis Console. KOBAS 3.0 and DAVID 6.8 were used for KEGG and GO analysis. Selected genes from microarray analysis were validated using qPCR.
RESULTS: There were 640 differentially expressed genes between both groups. The top ten upregulated genes were HMGCS2, UGT2A3 isoforms, B4GALNT2, MEP1B, GUCA2B, ADH1C, OTOP2, SLC9A3, and LYPD8; the top ten downregulated genes were PI3, DUOX2, VNN1, SLC6A14, GREM1, MMP1, CXCL1, TNIP3, TFF1, and LCN2. Among the 123 altered KEGG pathways, the most significant were metabolic pathways; fatty acid degradation; valine, leucine, and isoleucine degradation; the peroxisome proliferator-activated receptor signalling pathway; and bile secretion, which were previously linked with CAC. Analysis showed that 3560 genes exhibited differential alternative splicing between long- and short-duration UC. Among them, 374 were differentially expressed, underscoring the intrinsic relationship between altered gene expression and alternative splicing.
CONCLUSIONS: Long-duration UC patients have altered gene expressions, pathways, and alternative splicing events as compared with short-duration UC patients, and these could be further validated to improve our understanding of the pathogenesis of CAC.
CLINICAL FEATURES: A 44-year-old diabetic and alcoholic restaurateur of Chinese-Malay origin, who had been living in Australia for over 20 years, was admitted to hospital with bloody diarrhoea which progressed to fulminant toxaemia and circulatory collapse, and ultimately required laparotomy. Typical pathological features and the isolation of Clostridium perfringens type C from faeces confirmed the diagnosis of enteritis necroticans.
INTERVENTION AND OUTCOME: He was treated initially with ampicillin, gentamicin, metronidazole and chloramphenicol, and later with penicillin and metronidazole, and he required large volumes of intravenously administered fluid and blood for his toxaemic, hypotensive state. Laparotomy was performed as a life-saving procedure. Despite a lengthy convalescence, the patient recovered.
CONCLUSIONS: Enteritis necroticans is a rare disease in developed countries, however it is likely to be underdiagnosed. Clinicians are encouraged to be on the alert for signs of severity that may indicate the need for laparotomy in a predisposed individual with features of this condition.