Background: Patients with long duration ulcerative colitis (UC) patients have high risk of developing colitis-associated cancer (CAC). Chronic diseases including various types of cancer have been associated with aberrant alternative splicing (AS). However, data on AS in chronic IBD such as UC and CAC is still lacking. Aberrant alternative splicing (AS) has been linked with various types of cancer but its association with CAC has not been well defined. This study aimed to determine the crucial genes that are differentially spliced within the UC susceptibility loci in long duration UC as compared with short duration UC. Methods: To date, a total of 15 patients (11 with short duration <5 years and four with long duration >20 years) were recruited. During routine colonoscopy procedure, the inflammed colonic tissues were biopsied and RNA was extracted and hybridised to the Affymetrix GeneChip® Human Transcriptome Array 2.0. Affymetrix Transcriptome Analysis Console was used to identify AS events (splicing index>|1.5|, ANOVA p<0.05, false discovery rate<0.05). KOBAS 2.0 was used for KEGG and Gene Ontology analysis. Results: A total of 2,443 genes exhibited differential splicing between long duration UC and short duration UC. Alternate 3' acceptor, alternate 5' donor, cassette exon and intron retention events were reported. Both negative (range −1.51 to −143.98) and positive (range 1.51 to 204.48) splicing indexes were reported. Among these, 11 genes were IBD susceptibility loci (REL, STAT1, ERAP2, TRAF3IP2, PHACTR2, CNTF, VDR, RPS6KB1, CD226, HCK and TNFRSF6b) and three genes were UC-specific (NFKB1, SLC9A3 and HNF4A). The KEGG pathway and Gene Ontology analysis showed enrichment for immune regulatory and CAC pathways (p<0.05). Among all, JAK/STAT signalling pathway was the most prominent pathway which contains genes that were differentially spliced between long duration UC compared to short duration UC. Conclusions: This is the first study that has successfully discovered alternative splicing events in the crucial genes that possibly involved in the transformation of long duration UC to colitis associated cancer. Further validation is essential to confirm the alternative splicing events in order to understand the potential mechanisms in carcinogenesis derived from chronic ulcerative colitis.

Backgrounds. The aim of this study was to appraise the relationship between serum fragmented cytokeratin-18(CK-18), controlled attenuation parameter (CAP), and liver steatosis assessed by ultrasound (US) in nonalcoholic fatty liver disease (NAFLD) patients. Methods. Patients who underwent abdominal US were recruited, followed with measurement of CAP using Fibroscan 5 and serum fragmented CK-18 using enzyme-linked immunosorbent assay. The degree of liver steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). Results. A total of 109 patients were included in our study. CAP and fragmented CK-18 level were significantly correlated with liver steatosis grade with r(s) = 0.56 and 0.68, p=0.001, respectively. NAFLD Fibrosis Score was poorly correlated with liver steatosis grade (r(s)=-0.096, p=0.318). Using fragmented CK-18 level, area under receiver operating characteristic (AUROC) curves for S >= 2 and S >= 3 were excellent (0.82 and 0.84, respectively). Using CAP, AUROC curves for detection of S >= 2 and S >= 3 were good (0.76, 0.77, respectively). We also proposed cut-off value of CAP to detect S >= 2 and S >= 3 to be 263 and 319 db/m, respectively, and fragmented CK-18 level to detect S >= 2 and S >= 3 (194 and 294 U/L, respectively). Conclusions. Both the fragmented CK-18 level and the CAP, but not NAFLD Fibrosis Score, were well correlated with hepatic steatosis grade as assessed by US.

There is a lack of non-invasive screening modalities to diagnose chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). Thus, the aim of the present study was to determine the sensitivity and specificity of serum pepsinogen I (PGI), PGI: II, the PGI: II ratio and gastrin-17 (G-17) in diagnosing CAG and IM, and the correlations between these serum biomarkers and pre-malignant gastric lesions. A cross-sectional study of 72 patients (82% of the calculated sample size) who underwent oesophagealgastro-duodenos-copy for dyspepsia was performed in the present study. The mean age of the participants was 56.2 +/- 16.2 years. Serum PGI: I, PGI: II, G-17 and Helicobacter pylori antibody levels were measured by enzyme-linked immunosorbent assay. Median levels of PGI: I, PGI: II, the PGI: II ratio and G-17 for were 129.9 mu g/l, 10.3 mu g/l, 14.7 and 4.4 pmol/l, respectively. Subjects with corpus CAG/IM exhibited a significantly lower PGI: II ratio (7.2) compared with the control group (15.7; P< 0.001). Histological CAG and IM correlated well with the serum PGI: II ratio (r=-0.417; P<0.001). The cut-off value of the PGI: II ratio of <= 10.0 demonstrated high sensitivity (83.3%), specificity (77.9%) and area under the receiver operating characteristic curve of 0.902 in detecting the two conditions. However, the sensitivity was particularly low at a ratio of <= 3.0. The serum PGI: II ratio is a sensitive and specific marker to diagnose corpus CAG/IM, but at a high cut-off value. This ratio may potentially be used as an outpatient, non-invasive biomarker for detecting corpus CAG/IM.