G-protein signaling modulator 1 promotes colorectal cancer metastasis by PI3K/AKT/mTOR signaling and autophagy.

BACKGROUND: Colorectal cancer is the second most common malignant tumor worldwide. A deeper insight into the mechanisms underlying colorectal cancer metastasis is urgently needed. G-protein signaling modulator 1 and autophagy play critical roles in tumor migration and invasion. However, the biological functions and regulatory networks of G-protein signaling modulator 1 and autophagy have not yet been fully studied. METHODS: We performed immunohistochemistry and clinic-pathological characteristic analysis in 328 human colorectal cancer specimens to identify the clinical role of G-protein signaling modulator 1 in colorectal cancer. An in vitro coculture system and a tumor metastasis mouse model were used to explore the biological function of G-protein signaling modulator 1 on tumor metastasis. Autophagic flux detection like GFP-LC3B signal immunofluorescence and electron microscope observation of autophagic vesicles and confocal microscope detection were used to gain insights into the underlying role of G-protein signaling modulator 1 in autophagy. RESULTS: We found that G-protein signaling modulator 1 was abundantly expressed in colorectal cancer tissues and was associated with lymph node metastasis and poor prognosis. Furthermore, our bioinformatic and functional studies demonstrated that G-protein signaling modulator 1 significantly promoted cell migration and invasion, both in vitro and in vivo. Mechanistically, we demonstrated that G-protein signaling modulator 1 could promote colorectal cancer cell migration and invasion and inhibit autophagy and by activating the PI3K/AKT/mTOR pathway. CONCLUSIONS: We proposed that G-protein signaling modulator 1 promotes colorectal cancer metastasis by modulating autophagy through the PI3K/AKT/mTOR pathway.

Expression of TET2 and DNMT3A in peripheral T cell lymphoma and their significance / 临床与实验病理学杂志

Purpose To investigate the expression of TET2 and DNMT3A in patients with peripheral T cell lymphoma (PTCL) and the relationship to immunophenotypes of PTCL.Methods Using a panel of immunohistochemical markers (CD3,CD4,CD10,BCL-6,CXCL-13,CD30,ALK),all cases of PTCLs were further divided into four groups,including angioimmunoblastic T cell lymphoma (AITL),peripheral T cell lymphoma,not otherwise specified (PTCL-NOS),anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK-ALCL) and anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK + ALCL).The expression of TET2 and DNMT3A in 89 cases of PTCL was detected by immunohistochemical analysis.Results 89 cases were divide into four subtypes,AITL (36/89),PTCL-NOS (26/89),ALKALCL (18/89),and ALK + ALCL (9/89).Immunohistochemistry staining revealed higher cytoplasmic expression of TET2 and DNMT3A in AITL than that of in PTCL-NOS and ALCL (P ＜ 0.05).And the nuclear expression of DNMT3A in patients with AITL was higher than that of PTCL-NOS and ALCL (P ＜ 0.05).The cytoplasmic expression of TET2 was positively related with both cytoplasmic and nuclear expression of DNMT3A in patients with AITL (P ＜ 0.05).Conclusion TET2 combined with DNMT3A could be used as markers in AITL diagnosis,which could provide new strategy for AITL diagnosis.

Expression and significance of leptin receptor, p-STAT3 and p-AKT in diffuse large B-cell lymphoma.

We investigated the expression and clinical significance of leptin receptor (OBR), p-STAT3 and p-AKT in patients with diffuse large B-cell lymphoma (DLBCL) by immunohistochemical analysis. Immunohistochemistry revealed high expression of OBR, p-STAT3 and p-AKT in 45.0% (36/80), 28.8% (23/80) and 18.8% (15/80) cases of DLBCL, respectively, and minimal staining in 100% (20/20) cases of RLH (P<0.05). Compared with GCB group, the non-GCB group had higher p-STAT3 expression rate (21/57 vs. 2/23, P<0.01). The expression of OBR was positively related with that of p-STAT3 and p-AKT in DLBCL patients (P<0.05). Our data suggest that OBR stimulates the JAK/STAT and PI3K/AKT signaling pathway and induces the phosphorylation of STAT3 and AKT. This may be involved in carcinogenesis and prognosis of DLBCL. The specific inhibitions could interfere in the combination of leptin with OBR and obstruct the JAK/STAT and PI3K/AKT signaling pathways, which could lead to new research and treatment strategies for DLBCL treatment.

Dual-color silver-enhanced in-situ hybridization for determination of HER2 gene amplification in gastric carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the concordance of dual-color silver enhanced in-situ hybridization (DSISH) and immunohistochemistry (IHC) in the detection of HER2 gene amplification and expression and to evaluate the values of DSISH in detecting HER2 gene status in gastric carcinoma.</p><p><b>METHODS</b>By using automated DSISH and IHC, HER2 gene status was detected in 230 cases of gastric cancer.</p><p><b>RESULTS</b>Among the 230 cases of gastric carcinoma tested by DSISH, 43 cases were positive and 187 cases were negative; HER2 gene amplification rate was 18.7% (43/230). The expression of HER2 protein was negative, weakly, moderately and strongly positive in 115, 69, 15 and 31 cases, respectively, by IHC. HER2 protein positive rate was 13.5% (31/230). Of the 43 HER2 gene amplification cases by DSISH, 2, 10, 2 and 29 cases were negative, weakly, moderately and strongly positive by IHC; Of the 187 HER2 negative cases by DSISH, 113, 59, 13 and 2 cases were negative, weakly, moderately and strongly positive by IHC, respectively. The overall concordance of HER2 status in the investigation between IHC and DSIDH was 93.5% (201/215), with a high consistency (Kappa coefficient 0.767, P < 0.01).</p><p><b>CONCLUSIONS</b>DSISH can be applied to detect the HER2 gene status in gastric cancer and it also has a high consistency with the result of IHC. In addition, due to frequent heterogeneous expression of HER2, cases with moderate HER2 protein expression may need further assessment by DSISH.</p>

Expression and significance of leptin receptor and phosphorylation of signal transducer and activator of transcription 3 in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To investigate the expression and clinical significance of leptin receptor (OBR) and phosphorylation of signal transducer and activator of transcription (p-STAT3) in patients with diffuse large B-cell lymphoma (DLBCL).Methods Immunohistochemical analysis was used to detect the expression of OBR and p-STAT3 in 80 patients with DLBCL and 10 patients with reactive lymphoid hyperplasia (RLH).Using a panel of immunohistochemical markers (CD10,bcl-6 and Mum-1),all cases of DLBCL were further divided into two groups,GCB (germinal center B-cell-like) or non-GCB.Results Immunohistochemistry revealed high expression of OBR and p-STAT3 in 45.0 ％ (36/80) and 28.8 ％ (23/80) cases of DLBCL,respectively,and minimal straining in 100.0 ％ (10/10) cases of RLH (P ＜ 0.05).Compared with GCB group (8.7 ％,2/23),non-GCB group had higher p-STAT3 high expression rate (36.8 ％,21/57) (P ＜ 0.05).There was no significant difference in the expression of OBR between these two groups.Compared with clinical stage Ⅰ-Ⅱ [46.2 ％ (18/39) and 25.6 ％ (10/39)],stage Ⅲ-Ⅳ had higher OBR and p-STAT3 high expression rate [61.9 ％ (13/21) and 38.1％ (8/21)] (P ＞ 0.05).The expression of OBR and p-STAT3 were not correlated with age,gender,extranodal infiltrations,LDH level,B-symptoms and IPI(international prognostic index)(P ＞ 0.05).The expression of OBR was positively related with that of p-STAT3 in DLBCL patients (r =0.232,P =0.039).Conclusion OBR could stimulate the JAK-STAT signaling pathway and induces the phosphorylation of STAT3.This may be involved in carcinogenesis and prognosis of DLBCL.

Relationship between expressions of CXCR4, MMP-2 and VGEF and biological behavior of pancreatic cancer / 中华胰腺病杂志

Objective To investigate the expressions of CXCR4,MMP-2 and VEGF in pancreatic carcinoma and the relationship with biological behavior of pancreatic carcinoma.Methods Immunohistochemical PV6000 technique was used to detect the expression of CXCR4,MMP-2 and VEGF in 47 cases of pancreatic carcinoma tissues,and the relationship between the expressions and pathologic parameters,and the relationship among the expressions of the 3 proteins were analysed.Results The expression rates of CXCR-4,MMP-2 and VEGF were 72.3%,66.O%and 61.7%in pancreatic carcinoma tissues,and all these proteins were correlated with metastasis,clinical staging and prognosis(X2=5.84～12.69;P＜0.05).The expression of CXCR-4,MMP-2 and VEGF was not correlated with sex,age,tumor size and differentiation(X2=0.03～4.27;P＞0.05).There was a positive relationship between the expression of CXCR-4 and MMP-2 or VEGF in pancreatic carcinoma(r=0.587,0.521;P＜0.01).Conclusions CXCR-4 could up-regulate the expression of MMP-2 and VEGF in pancreatic carcinoma,and they may contribute to metastasis and invasion of pancreatic carcinoma.