BackgroundDespite recent advances in colorectal cancer (CRC) diagnosis and population screening programs, the identification of patients with preneoplastic lesions or with early CRC stages remains challenging and is important for reducing CRC incidence and increasing patient’s survival. MethodsWe analysed 76 colorectal tissue samples originated from early CRC stages, normal or inflamed mucosa by label-free proteomics. The characterisation of three selected biomarker candidates was performed by immunohistochemistry on an independent set of precancerous and cancerous lesions harbouring increasing CRC stages.ResultsOut of 5258 proteins identified, we obtained 561 proteins with a significant differential distribution among groups of patients and controls. KNG1, OLFM4 and Sec24C distributions were validated in tissues and showed different expression levels especially in the two early CRC stages compared to normal and preneoplastic tissues.ConclusionWe highlighted three proteins that require further investigations to better characterise their role in early CRC carcinogenesis and their potential as early CRC markers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9143-3) contains supplementary material, which is available to authorized users.

Background and aims Intestinal fibrosis is a common complication of Crohn’s disease (CD). It is characterised by an accumulation of fibroblasts differentiating into myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods We performed a pilot proteomic study comparing the proteome of surface epithelium, isolated by laser-capture microdissection, in normal and fibrotic zones of resected ileal CD strictures (13 zones collected in 5 patients). Proteins of interests were validated by immunohistochemistry (IHC) in ileal and colonic samples of stricturing CD (n=44), pure inflammatory CD (n=29) and control (n=40) subjects. The pro-fibrotic role of one selected epithelial protein was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. Results Proteomic study revealed an endoplasmic reticulum (ER) stress proteins increase in the epithelium of CD ileal fibrotic strictures, including Anterior gradient protein 2 homolog (AGR2) and Binding-immunoglobulin protein (BiP). This was confirmed by IHC. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2 intracellular expression and its secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin, led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. By using recombinant protein and blocking agent for AGR2, we demonstrated that the secretion of this protein by epithelial cells can play a role in the myofibroblastic differentiation. Conclusions The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2.

Background and Aims Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. Methods A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. Results Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed “loss of gradient” reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 – 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. Conclusions We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.

Background. The severity of endoscopic recurrence during the first year after intestinal resection for Crohn’s disease is predictive of clinical recurrence. The aim of our study was to assess the impact of the implementation of an ileocolonoscopy during the first year after surgery on surgical recurrence. Methods. All patients who underwent a first intestinal resection for Crohn’s disease between 1992 and 2018 at the University Hospital of Liège were retrospectively included. The time to surgical recurrence was compared in three successive groups of patients operated on in the period 1992–2001 (group A), 2002–2011 (group B), and 2012–2020 (group C) using the Kaplan–Meier method and the Log-Rank test. To identify independent prognostic factors, a multivariate analysis was used via the Cox model. Results. 223 patients (group A = 69, group B = 94, group C = 60) were included. Probabilities of surgical recurrence were significantly lower in group C (2.2% and 4.7% at 3 and 5 years, respectively) compared with group B (4.2% and 7.6% at 3 and 5 years, respectively) and with group A (9% and 18.2% at 3 and 5 years, respectively) ( p = 0.0089 ). Ileocolonoscopy during the year after surgery was associated with a significantly reduced surgical recurrence rate in univariate and multivariate analysis (HR = 0.31, p = 0.0049 ). Conclusion. The implementation of an early ileocolonoscopy after surgery for Crohn’s disease since early 2000 has been associated with a reduced surgical recurrence over the last 30 years.