scholarly journals High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer

2017 ◽  
Vol 23 ◽  
pp. 6033-6041 ◽  
Author(s):  
Fangpeng Ye ◽  
Peisheng Jin ◽  
Xiaoniao Cai ◽  
PeiPei Cai ◽  
Huimin Cai
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14670-e14670
Author(s):  
Metin Ozkan ◽  
Esra Ermis Turak ◽  
Halit Karaca ◽  
Mevlude Inanc ◽  
Veli Berk ◽  
...  

e14670 Background: HER-2 and Topo-2A genes are settled on a chromosome 17 and their co-amplification rates are high. In this study, early gastric cancer patients who received adjuvant chemo-radiotherapy and chemotherapy were evaluated with HER-2 and Topo-2A expression in association with clinical and histopathologic findings. Methods: A total of 103 gastric cancer patients were included the study. The HER-2 and Topo-2A levels were measured by immunohistochemistry in postoperative tumor materials. A standard evaluation method was admitted for HER-2 positivity, while Topo-2A nuclear staining 3+ and 4+ were considered as overexpression. Those with level 2+ or 3+ of HER-2, the FISH test were attempted. Results: The median follow-up was 19 months (ranges 2–70 months). Forty-six patients (44%) relapsed during follow-up whereas 60 patients (58%) had died. The median overall survival (mOS) was 23 months. Histopathologies of HER-2 positive patients were intestinal type in 7 (87.5%) and diffuse type in one (12.5%) patient. In the follow-up period 4 patients (50%) were died (mOS was 17 months in this group). Median overall survival was 23 months in HER-2 negative group (p=0.6). Histopathologies of Topo-2A positive patients were intestinal type in 9 (64.2%) and diffuse type in 5 (35.8%) patient. In the follow-up period 8 patients (57%) were died (mOS was 22 months in this group). Median overall survival was 23 months in Topo-2A negative group (p=0.8). Three patients (37.5%) who had HER-2 positive histopathologies also had Topo-2A positivity. Conclusions: Overexpression rates of HER-2 in gastric cancer were reported 6.8-34%. Racial differences and different scoring techniques thought to be impact the results. Co-amplification rate of HER-2 and Topo-2A was reported 34% in gastric cancer. In our study HER-2 and Topo-2A overexpression rates were 7.7% and 13.6% respectively and co-amplification of HER-2 with Topo-2A rate was 37.5% is also similar to the other studies. Stages of patients with HER-2 and Topo-2A overexpression were similar to the distribution of the overall patients. While intestinal subtypes showed a higher rate of HER-2 overexpression, the median survival times tend to be shorter in HER-2 positive patients.


Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769454 ◽  
Author(s):  
Takahiko Kobayashi ◽  
Junich Ishida ◽  
Yuichi Shimizu ◽  
Hiroshi Kawakami ◽  
Goki Suda ◽  
...  

RNA-binding motif 5 is a putative tumor suppressor gene that modulates cell cycle arrest and apoptosis. We recently demonstrated that RNA-binding motif 5 inhibits cell growth through the p53 pathway. This study evaluated the clinical significance of RNA-binding motif 5 expression in gastric cancer and the effects of altered RNA-binding motif 5 expression on cancer biology in gastric cancer cells. RNA-binding motif 5 protein expression was evaluated by immunohistochemistry using the surgical specimens of 106 patients with gastric cancer. We analyzed the relationships of RNA-binding motif 5 expression with clinicopathological parameters and patient prognosis. We further explored the effects of RNA-binding motif 5 downregulation with short hairpin RNA on cell growth and p53 signaling in MKN45 gastric cancer cells. Immunohistochemistry revealed that RNA-binding motif 5 expression was decreased in 29 of 106 (27.4%) gastric cancer specimens. Decreased RNA-binding motif 5 expression was correlated with histological differentiation, depth of tumor infiltration, nodal metastasis, tumor–node–metastasis stage, and prognosis. RNA-binding motif 5 silencing enhanced gastric cancer cell proliferation and decreased p53 transcriptional activity in reporter gene assays. Conversely, restoration of RNA-binding motif 5 expression suppressed cell growth and recovered p53 transactivation in RNA-binding motif 5–silenced cells. Furthermore, RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer.


2021 ◽  
pp. 1-8
Author(s):  
Masakazu Yashiro ◽  
Tsuyoshi Hasegawa ◽  
Yurie Yamamoto ◽  
Gen Tsujio ◽  
Sadaaki Nishimura ◽  
...  

<b><i>Background:</i></b> Asporin (ASPN), a member of the proteoglycan family, has been shown to have a close correlation with cancer progression. It is not known whether ASPN is an oncogenic driver or a tumor suppressor in human gastric cancer. We sought herein to determine the relationship between ASPN expression and clinicopathological features of gastric cancer. <b><i>Patients and Methods:</i></b> A total of 296 gastric cancer patients (diffuse type, <i>n</i> = 144; intestinal type, <i>n</i> = 152) were enrolled. The ASPN expression level in each case was analyzed by immunohistochemistry. <b><i>Results:</i></b> ASPN was mainly found on stromal cells, especially on fibroblasts in tumor stroma, i.e., cancer-associated fibroblasts. The ASPN expression on either cancer cells or stromal cells was significantly high in macroscopic scirrhous-type tumors (<i>p</i> &#x3c; 0.001) and histologically abundant stroma-type tumors (<i>p</i> &#x3c; 0.001). Interestingly, a Kaplan-Meier survival curve of the 144 cases of diffuse-type gastric cancer revealed a significantly poorer prognosis in patients with ASPN-positive expression (<i>p</i> = 0.043; log rank) compared to those with ASPN-negative expression, but the prognoses were not significantly different in these subgroups of the 152 cases of intestinal-type gastric cancer. A multivariate analysis with respect to overall survival showed that ASPN expression on stromal cells and/or cancer cells was significantly correlated with overall survival in patients with diffuse-type gastric cancer (<i>p</i> = 0.041). <b><i>Conclusion:</i></b> In gastric cancer, ASPN was expressed mainly on stromal cells and partially on cancer cells. ASPN expression on stromal cells and/or cancer cells might be a useful prognostic marker in patients with diffuse-type gastric cancer.


2017 ◽  
Vol 58 (3-4) ◽  
pp. 158-168 ◽  
Author(s):  
Kyueng-Whan Min ◽  
Dong-Hoon Kim ◽  
Byoung Kwan Son ◽  
Dong Hyun Kim ◽  
Eun-Kyung Kim ◽  
...  

Background: The heterogeneity of gastric cancer makes the identification of potential prognostic indicators particularly important. The Ki67 and BCL2 proteins are known prognostic markers for different types of cancer. Ki67 is associated with cell proliferation, whereas BCL2 has antiproliferative roles. A combined marker based on these opposite functions might provide improved prognostic information in gastric cancer. Method: Ki67 and BCL2 expression was assessed in 276 gastric adenocarcinoma tissue microarrays. A Ki67/BCL2 index based on the relative expression of each protein was divided into low- and high-risk groups using receiver operating characteristic curves. Results: A high Ki67/BCL2 index significantly correlated with advanced stage, recurrence, intestinal type, high histologic grade, and lymphatic and perineural invasion (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between disease-free or overall survival and the Ki67/BCL2 index in intestinal-type gastric cancer (all p < 0.05). Conclusions: A combined marker using Ki67 and BCL2 could be a useful indicator for predicting survival in patients with intestinal-type gastric cancer.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sang Hoon Chun ◽  
Eun Young Kim ◽  
Jung-Sook Yoon ◽  
Hye Sung Won ◽  
Kwangil Yim ◽  
...  

Abstract Background Noggin and RNA-binding protein for multiple splicing 2 (RBPMS2) are known to regulate the expression of smooth muscle cells, endothelial cells, and osteoblasts. However, the prognostic role of combined Noggin and RBPMS2 expression in resected gastric cancer (GC) is unclear. Methods A total of 163 patients with GC who underwent gastrectomy were included in this study. The expression of Noggin and RBPMS2 proteins in tumor cells at the tumor center and invasive front of resected GC was evaluated by immunohistochemistry, and in conjunction with clinicopathological parameters the patient survival was analyzed. Results RBPMS2 protein expression was high at the tumor center (n = 86, 52.8%) and low at the invasive front (n = 69, 42.3%), while Noggin protein expression was high in both tumor center (n = 91, 55.8%) and the invasive front (n = 90, 55.2%). Noggin expression at the invasive front and tumor center was significantly decreased in advanced T stage, non-intestinal-type (invasive front, P = 0.008 and P <  0.001; tumor center lesion, P = 0.013 and P = 0.001). RBPMS2 expression at the invasive front was significantly decreased in non-intestinal-type and positive lymphatic invasion (P <  0.001 and P = 0.013). Multivariate analysis revealed that high Noggin protein expression of the invasive front was an independent prognostic factor for overall survival (hazard ratio [HR], 0.58; 95% confidence interval [CI]; 0.35–0.97, P <  0.036), but not at the tumor center (HR, 1.35; 95% CI; 0.81–2.26, P = 0.251). Conclusions Our study indicates that high Noggin expression is a crucial prognostic factor for favorable outcomes in patients with resected GC.


2021 ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods : A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036); KK-LC-1 protein is more highly expressed in the intestinal type than the diffuse type, and it is statistically significant. The high expression of KK-LC-1 protein in the intestinal type is more than that in the diffuse type (P =0.008). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.


2021 ◽  
Vol 4 (4) ◽  
pp. e202000884
Author(s):  
Diego Peretti ◽  
Heather L Smith ◽  
Nicholas Verity ◽  
Ibrahim Humoud ◽  
Lis de Weerd ◽  
...  

Increasing levels of the cold-shock protein, RNA-binding motif 3 (RBM3), either through cooling or by ectopic over-expression, prevents synapse and neuronal loss in mouse models of neurodegeneration. To exploit this process therapeutically requires an understanding of mechanisms controlling cold-induced RBM3 expression. Here, we show that cooling increases RBM3 through activation of TrkB via PLCγ1 and pCREB signaling. RBM3, in turn, has a hitherto unrecognized negative feedback on TrkB-induced ERK activation through induction of its specific phosphatase, DUSP6. Thus, RBM3 mediates structural plasticity through a distinct, non-canonical activation of TrkB signaling, which is abolished in RBM3-null neurons. Both genetic reduction and pharmacological antagonism of TrkB and its downstream mediators abrogate cooling-induced RBM3 induction and prevent structural plasticity, whereas TrkB inhibition similarly prevents RBM3 induction and the neuroprotective effects of cooling in prion-diseased mice. Conversely, TrkB agonism induces RBM3 without cooling, preventing synapse loss and neurodegeneration. TrkB signaling is, therefore, necessary for the induction of RBM3 and related neuroprotective effects and provides a target by which RBM3-mediated synapse-regenerative therapies in neurodegenerative disorders can be used therapeutically without the need for inducing hypothermia.


2020 ◽  
Author(s):  
Shuhei Kushiyama ◽  
Masakazu Yashiro ◽  
Yurie Yamamoto ◽  
Tomohiro Sera ◽  
Atsushi Sugimoto ◽  
...  

Abstract Background: Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein expressed in epithelial cells. TROP2 overexpression has been reported to be correlated with malignant progression in most carcinomas, but TROP2 showed a tumor-suppressive function in some types of cancers. We currently developed a novel antibody against phospho-TROP2 (pTROP2). Since the function of TROP2 is controversial, we then aimed to clarify the clinicopathologic significance of TROP2 and pTROP2 expression in human gastric cancer (GC) in this study.Methods: We retrospectively analyzed the cases of 704 GC patients who underwent gastrectomy. The expressions of TROP2 and pTROP2 in each tumor were evaluated by immunohistochemistry. We analyzed the correlation between the GC patients' clinicopathologic features and the TROP2 and pTROP2 expression in their tumors.Results: Overexpression of TROP2 and that of pTROP2 were identified in 330 (46.9%) and 306 (43.5%) of the 704 GC patients, respectively. TROP2 overexpression was significantly correlated with the histological intestinal type, high tumor invasion depth (T3/T4), lymph node metastasis, lymphatic invasion, and venous invasion. In contrast, pTROP2 overexpression was significantly correlated with intestinal type, low tumor invasion depth (T1/2), no lymph node metastasis, and no lymphatic invasion. TROP2 overexpression was significantly associated with poorer overall survival (p<0.01, log rank), whereas pTROP2 overexpression was significantly associated with better overall survival (p<0.01, log rank).Conclusion: TROP2, but not pTROP2, might be associated with the metastatic ability of GC, resulting in poor prognoses for GC patients.


2019 ◽  
Vol 25 ◽  
pp. 4025-4034 ◽  
Author(s):  
Hongmei Yong ◽  
Wei Zhao ◽  
Xueyi Zhou ◽  
Zhenyun Liu ◽  
Qi Tang ◽  
...  

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