HSP4 triggers epithelial-mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT.

BACKGROUND AND AIMS: Heat shock factor (HSF4) plays a vital role in carcinogenesis and tumour progression. However, its clinical significance implications in hepatocellular carcinoma (HCC) remained elusive. METHODS: RT-PCR and western blot were used to detect the HSF4 expression levels in HCC cells and tissues. Immunohistochemistry staining was performed on a tissue microarray containing 104 HCC patients received radical resection. In vitro effects of HSF4 on proliferation, migration and invasion were determined by colony formation and transwell assays in HCCLM3, Huh7, MHCC97L and SMMC7721 cells. Epithelial-mesenchymal transition (EMT) was identified by RT-PCR, WB and immunofluorescence in HCCLM3 and MHCC97L cells. AKT pathway activation was detected by WB and dual luciferase report system in HCCLM3 and MHCC97L cells. RESULTS: HSF4 expression was higher in primary HCC tissues derived from recurrent patients, and positively correlated with invasiveness potentials of cell lines. Clinically, patients with high HSF4 expression had significant poorer prognosis. In vitro experiments showed HSF4 silencing inhibited HCC cell proliferation, migration and invasion, whereas HSF4 overexpression had inverse effects. Moreover, silence of HSF4 induced an epithelial-like phenotype, whereas the overexpression of HSF4 resulted in a mesenchymal-like phenotype in HCC by activating AKT pathway. Further experiments showed that HSF4 could activate AKT pathway in a hypoxia-inducible factor-1α (HIF-1α) dependent, but transforming growth factor-ß (TGF-ß) independent manner. CONCLUSIONS: HSF4 is upregulated in HCC, resulting in greater proliferation, migration and invasion capacities. Moreover, high HSF4 expression is a promising predictive indicator of poor outcome after radical resection. HSF4 may promote aggressive tumour behaviour by enhancing EMT through activating AKT pathway in a HIF1α-dependent manner.

[The clinical, endoscopic and pathologic features of Crohn's disease in the differentiation from intestinal tuberculosis].

OBJECTIVE: To investigate the clinical, endoscopic and pathologic features in the differential diagnosis between Crohn's disease(CD) and intestinal tuberculosis (ITB). METHODS: The complete clinical data of 107 patients with CD and 69 patients with ITB in our hospital from January 2011 to January 2012 were retrospectively analyzed. The diagnostic value of the clinical and endoscopic scoring system was evaluated. RESULTS: CD occurred mainly in male. The salient features of CD included long duration of disease high incidence of colectomy. Comparing with patients with ITB, patients with CD have more cases of diarrhea, hematochezia, abdominal mass, intestinal obstruction, intestinal hemorrhage, perianal lesions, and extraintestinal manifestations (all P < 0.05).It's more frequent to have positive results of anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear antineutrophil cytoplasmic antibody (pANCA) and fecal occult blood in CD patients, as well as low albumin, high C-reactive protein ( CRP), elevated platelet count and hematocrit (P < 0.05 or P < 0.01). The salient features of ITB included low fever, night sweats, active parenteral tuberculosis, increased erythrocyte sedimentation rate (ESR), chest X-ray abnormalities, the positive PPD (purified protein derivatives tuberculin) and T-SPOT (P < 0.05 or P < 0.01). Based on the imaging, CD often involved the small intestine, such as the intestinal stricture and abdominal abscess (P < 0.05), while mesenteric lymphadenopathy was more common in ITB (P < 0.05). The endoscopic examination showed that some patterns of disease involvement such as fissure-shape ulcer [41.12% (44/107) vs 5.80% (4/69)], cobblestone sign[15.89% (17/107) vs 4.35% (3/69)], lesions over four segment [24.30% (26/107) vs 7.25% (5/69)], rectum involvement [17.76% (19/107) vs 5.80% (4/69)], ileocecal valve stenosis [21.50% (23/107) vs 8.70% (6/69)] and mucosal bridge[5.61% (6/107) vs 0(0/69)] were more frequent in CD patients than those in ITB patients(P < 0.01 or P < 0.05). However circular ulcers[37.68% (26/69) vs 9.35% (10/107)], rat-bite-like ulcers[24.64% (17/69) vs 12.15% (13/107)], persistent open ileocecal valves [39.13% (27/69) vs 19.63% (21/107)], tuberous and polypoid lesions[36.23% (25/69) vs 20.56% (22/107), 37.68% (26/69) vs 22.43% (24/107)] were more common in ITB (P < 0.01 or P < 0.05). In terms of pathological findings, certain characteristic features such as transmural inflammation [5.61% (6/107) vs 0(0/69)], fissure-liked ulcers [14.02% (15/107) vs 4.35% (3/69)], non-caseous granulomas [5.61% (6/107) vs 0(0/69)], lymphoid hyperplasia [16.82% (18/107) vs 5.80% (4/69)] and crypt abscess [9.35% (10/107) vs 1.45% (1/69)] were more common in CD than those in ITB(P < 0.05). According to the clinical and endoscopic scoring system, the positive diagnostic rate of CD was 50.47% (54/107) and of ITB was 66.67% (46/69) (P < 0.05) . CONCLUSIONS: The differential diagnosis between CD and ITB should be considered carefully based on clinical, endoscopic, pathological characteristics. The clinical and endoscopic scoring system may contribute to distinguish CD and ITB.