Poor Prognosis In Gastric Cancer Research Articles

Value of Visceral Fat Area in the Preoperative Discrimination of Peritoneal Metastasis from Gastric Cancer in Patients with Different Body Mass Index: A Prospective Study.

PurposeAlthough peritoneal metastasis (PM) is associated with poor prognosis in gastric cancer (GC) patients, it is difficult to discriminate preoperatively. Our previous study has demonstrated visceral fat area (VFA) is a better obesity index than body mass index (BMI) in predicting abdominal metastasis. This study aimed to further explore the relationship between obesity and PM.Patients and MethodsVFA was retrieved for 859 consecutive patients undergoing radical gastrectomy between January 1, 2009, and December 31, 2013. A receiver operating characteristic curve analysis was used to determine the BMI-specific cutoff values for VFA. Univariate and multivariate analyses evaluating the risk factors for PM at different BMI levels were performed.ResultsThe optimal cutoff values for VFA were 67.28, 88.03, and 175.32 cm2 for low, normal, and high BMI patients, respectively, and 18 (15.52%), 220 (40.15%), and 61 (31.28%) patients were classified as having high VFA in each group. Univariate logistic regression revealed that the association between high VFA and PM was not dependent on BMI (odds ratio [OR]=9.048, P=0.007 for low BMI, OR=3.827, P<0.001 for normal BMI, and OR=2.460, P=0.049 for high BMI). In multivariate logistic regression analysis, high VFA (OR=3.816, P<0.001) and vascular invasion (OR=1.951, P=0.039) were independent risk factors for PM only in the normal BMI group.ConclusionVFA only effectively predicted PM for GC patients with normal BMI, rather than those with low and high BMI. More attentions should be paid to those GC patients with high VFA and normal BMI.

Prognostic Significance of ADAM17 for Gastric Cancer Survival: A Meta-Analysis.

Background and objectives: The prognostic role of a disintegrin and metalloproteinase (ADAM) 17 has been widely assessed in gastric cancer. However, the results are inconsistent. We performed a meta-analysis to evaluate the prognostic significance of ADAM17 and its association with clinicopathological parameters. Methods: The databases of PubMed, Web of Science, and Embase were searched for relevant articles published up to April 2020. The reported hazard ratios (HRs) and odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were pooled to evaluate the strength of the association. Stata 12.1 was used to perform statistical analyses. Results: Seven studies, including 1757 patients, were screened for the meta-analysis. Compared with the high ADAM17 expression group, the pooled HR was higher in the low ADAM17 expression group (HR = 2.04, 95% CI 1.66–2.50; I2 = 18.1%; p = 0.299). High ADAM17 expression was also related to the tumor node metastasis (TNM) stages (OR = 4.09, 95% CI 1.85–9.04; I2 = 84.1%; p = 0.000), lymph node metastasis (OR = 3.08, 95% CI 1.13–8.36; I2 = 79.7%; p = 0.007), and ages (OR = 1.65, 95% CI 1.24–2.21; I2 = 0%; p = 0.692) of the gastric patients. Conclusions: This meta-analysis revealed that ADAM17 is a significant biomarker for poor prognosis in gastric cancer.

Bmi-1-induced miR-27a and miR-155 promote tumor metastasis and chemoresistance by targeting RKIP in gastric cancer

BackgroundWe previously reported an inverse relationship between B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and Raf kinase inhibitory protein (RKIP), which is associated with the prognosis of gastric cancer (GC). In this study, we further explored the microRNA (miRNA) regulatory mechanism between Bmi-1 and RKIP.MethodsMicroarray analysis was first carried out to identify miRNA profiles that were differentially expressed in cells overexpressing Bmi-1. Then, miRNAs that could regulate RKIP were identified. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to measure the expression of Bmi-1, miR-155, miR-27a and RKIP. RKIP was confirmed as a target of miR-27a and miR-155 through luciferase reporter assays, qRT-PCR and Western blotting. The effects of the Bmi-1/miR-27a/RKIP and Bmi-1/miR-155/RKIP axes on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo.ResultsThe downregulation of RKIP by Bmi-1 occurred at the protein but not mRNA level. This indicates probable posttranscriptional regulation. miRNA expression profiles of cells with ectopic expression of Bmi-1 were analyzed and compared to those of control cells by microarray analysis. A total of 51 upregulated and 72 downregulated miRNAs were identified. Based on publicly available algorithms, miR-27a and miR-155 were predicted, selected and demonstrated to target RKIP. Bmi-1, miR-27a and miR-155 are elevated in human GC and associated with poor prognosis of GC, while RKIP is expressed at lower levels in GC and correlated with good prognosis. Then, in vitro tests shown that in addition to regulating RKIP expression via miR-27a and miR-155, Bmi-1 was also able to regulate the migration, invasion, proliferation, colony-formation ability and chemosensitivity of GC cells through the same pathway. Finally, the in vivo test showed similar results, whereby the knockdown of the Bmi-1 gene led to the inhibition of tumor growth, metastasis and chemoresistance through miR-27a and miR-155.ConclusionsBmi-1 was proven to induce the expression of miR-27a and miR-155 and thus promote tumor metastasis and chemoresistance by targeting RKIP in GC. Overall, miR-27a and miR-155 might be promising targets for the screening, diagnosis, prognosis, treatment and disease monitoring of GC.

Noggin is associated with a poor prognosis of gastric cancer by promoting the proliferation of gastric cancer cells via the upregulation of EGFR.

Noggin is an antagonist of bone morphogenetic proteins(BMP), being indispensable for certain developmental events. The present study aimed to examine the role of Noggin in the development and prognosis of gastric cancer(GC) and to elucidate the underlying mechanisms. The expression of Noggin in GC was evaluated by RT‑qPCR, immunohistochemistry and by the analyses of publicly available databases. The effects of Noggin on proliferation, cell cycle, adhesion, invasion, colony formation and tumour spheroid were examined following both the knockdown and overexpression of Noggin in GC cell lines. The involvement of epidermal growth factor receptor(EGFR) signalling was examined by western blot analysis and by using small molecule inhibitors. As a result, a higher expression of Noggin in GC was found to be associated with a poorer overall survival. Noggin overexpression promoted the proliferation and colony formation of GC cells by promoting cell cycle progression. The knockdown of Noggin in HGC27 cells exerted an opposite effect on proliferation, colony formation and cell cycle progression. Noggin expression positively correlated with EGFR expression in both GC cell line models and The Cancer Genome Atlas human GC cohort. Targeting EGFR and its downstream pathways diminished cell proliferation which was promoted by Noggin. Furthermore, Noggin overexpression resulted in an enhanced nuclear translocation of β‑catenin, leading to an upregulation of EGFR. Thus, the findings of the present study demonstrate that Noggin promotes the proliferation of GC cells by upregulating EGFR and enhancing a vicious circle formed by β‑catenin, EGFR, ERK and Akt.

Downregulation of TRIM27 suppresses gastric cancer cell proliferation via inhibition of the Hippo-BIRC5 pathway

Although tripartite motif containing 27 (TRIM27) protein has been implicated in the progression of many cancer types, its role in gastric cancer (GC) remains poorly understood. Given that TRIM27 may be associated with the baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) gene, which is downstream of the Hippo pathway, we clarified their relationship in GC progression. In vitro cultures of 7 GC cell lines, 92 GC patient tumor samples and 46 normal clinical samples were used to examine the influence of changes in TRIM27 expression, which was assessed by quantitative PCR, immunohistochemistry, western blot analysis, and cell viability assays. We found that TRIM27 overexpression was correlated with tumor size, depth of invasion, and poor GC prognosis, while TRIM27 small interfering RNA knockdown inhibited cell proliferation and colony formation, induced apoptosis, and increased sensitivity towards 5-fluorouracil treatment in MGC-803 and HGC-27 GC cell lines. Notably, TRIM27 downregulation resulted in BIRC5 suppression via large tumor suppressor kinase 2 (LATS2) upregulation and subsequent Yes-associated protein 1 (YAP1) inhibition in MGC-803 and HGC-27 GC cell lines. In conclusion, our findings revealed the positive correlation between TRIM27 and GC progression through mediation of the Hippo-BIRC5 axis in GC.

Increased expression of EHMT2 associated with H3K9me2 level contributes to the poor prognosis of gastric cancer.

Di-methylated lysine 9 of histone H3 (H3K9me2), regulated by histone methyltransferases, is involved in the epigenetic regulation of tumor-associated genes. The present study aimed to evaluate whether the H3K9me2 methylation level is associated with the expression level of euchromatic histone lysine methyltransferase 2 (EHMT2) in the prognosis of gastric cancer (GC). H3K9me2 methylation level and EHMT2 expression level were detected by immunohistochemistry in 118 GC samples. The clinicopathological significance of H3K9me2 and EHMT2 in patients with GC was assessed using a paired Student's t-test, χ2 test, Kaplan-Meier analysis with a log-rank test and Cox's proportional hazard analysis. Strong positive immunostaining of H3K9me2 and EHMT2 was observed in cancerous tissues compared with adjacent non-cancerous tissues. Positive immunostaining of EHMT2 and H3K9me2 was associated with lymph node metastasis, pathological grade and tumor-node-metastasis stage. H3K9me2 expression level was increased in tumor tissue and associated with worse specific-disease and disease-free survival time. In addition, EHMT2 protein expression levels were associated with the expression levels of H3K9me2. Low expression levels of H3K9me2 and EHMT2 predicted a better prognosis of patients with GC. The survival time of patients with a high expression of H3K9me2 and/or EHMT2 was significantly shorter compared with that of the patients with a low expression of H3K9me2 and/or EHMT2. In conclusion, an overexpression pattern of H3K9me2 and/or EHMT2 may be associated with clinicopathological features of GC and may be predictor markers of progression and prognosis in patients with GC, in addition to putative therapeutic targets.

Intralymph Node Expressions of A2AR and PD-L1 Were Associated with Metastasis and a Poor Prognosis in Gastric Cancer

Lymph node metastasis is an independent risk factor for survival of gastric cancer, but the underlying mechanism remains unclear. Adenosine (ADO) plays an immune regulation role through binding to adenosine receptors (ARs), especially A2AR. PD-L1 plays a key role in the immune escape of tumor. However, the expression of these two indicators in lymph nodes of gastric cancer has been rarely studied. Lymph node samples of 95 gastric cancer patients, including metastatic lymph nodes and matched non-metastatic lymph nodes were collected. Expression of A2AR and PD-L1 were detected with immunohistochemistry. The relationships among their expression with clinicopathological factors and prognostic parameters were analyzed as well. The expressions of A2AR and PDL-1 were both higher in metastatic lymph node than matched non-metastatic lymph node. The expression of A2AR in metastatic lymph nodes of gastric cancer was positively correlated with PD-L1. Positive expressions of A2AR and PDL-1 were associated with tumor N stage and prognostic parameters. There was no significant relationship with other clinicopathological characteristics. Our obtained data suggested that the high expressions of A2AR and PD-L1 were associated with the lymph node metastasis and a poor prognosis in gastric cancer, which may be a potential diagnostic and a therapeutic target for gastric cancer.

Retraction Note: MALAT2-activated long noncoding RNA indicates a biomarker of poor prognosis in gastric cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Transketolase-Like Protein 1 and Glucose Transporter 1 in Gastric Cancer

Background: The glucose metabolism of cancer cells differs from that of noncancerous cells. Transketolase-like protein 1 (TKTL1) and glucose transporter 1 (GLUT1) both play a role in this process. These biochemical tumor markers are overexpressed in several types of human cancer. Objective: We sought to determine if TKTL1 and/or GLUT1 expression predicts prognosis in gastric cancer. Methods: In this retrospective study, we selected 284 patients who underwent surgery for gastric cancer at the Helsinki University Hospital. We used immunohistochemistry to assess the expression of TKTL1 and GLUT1, combined with clinicopathological data. Results: Positive expression of TKTL1 was associated with positive expression of GLUT1, age over 65 years, male gender, advanced stage (II–IV), and advanced tumors (T2–T4). Patients with a positive expression of TKTL1 had a poorer prognosis than those with no expression (p = 0.042, Breslow test). GLUT1 positivity was associated with higher age and with the intestinal type of gastric cancer but did not carry any prognostic value. Conclusion: In conclusion, our study showed that positive expression of TKTL1 correlates with a poor prognosis in gastric cancer.

Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells.

SummaryHuman pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth.

High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer.

RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.

Rab7 Is Associated with Poor Prognosis of Gastric Cancer and Promotes Proliferation, Invasion, and Migration of Gastric Cancer Cells.

BackgroundRab7 belongs to the Ras oncogene family. Many studies have shown that its dysfunction is associated with many types of malignant tumors, but its effect on the pathogenesis of gastric cancer (GC) is still unknown. Therefore, we investigated the effect and mechanism of Rab7 in GC.Material/MethodsThe expression of Rab7 in GC and adjacent tissues was detected by immunohistochemistry, Western blot analysis, and qRT-PCR. The relationship of Rab7 with clinicopathological parameters and prognosis was analyzed. The expressions of Rab7, PI3K, and AKT in GC cells were assessed by Western blot. Overexpressed and silenced GC cell lines were constructed and AGS cells were treated with LY294002. The proliferation capacity of GC cells was detected by CCK8 assay, cell cycle changes were detected by flow cytometry, and the invasion and migration abilities of GC cells were assessed by transwell assay.ResultsThe expression of Rab7 was upregulated in the samples and cells, and was positively correlated with lymph node metastasis but negatively correlated with histological differentiation and clinical prognosis. In cell function experiments, overexpression of Rab7 induced the transition from S phase to G2 phase and promoted the proliferation, invasion, and migration of GC cells. Our assessment of the molecular mechanism showed that Rab7 promoted the phosphorylation of PI3K and AKT in GC cells. Incubation with the PI3K inhibitor Ly294002 impaired the enhanced effect of Rab7 overexpression on proliferation, migration, and invasion abilities of GC cells. These results show that the Rab7 affects GC cell progression by modulating the PI3K/AKT pathway.ConclusionsRab7 could be a prognostic biomarker and therapeutic target of the PI3K/AKT pathway in GC.

Clinical and prognostic association of oncogene cadherin 11 in gastric cancer.

The abnormal expression of cadherin-11 (CDH11) affects the progression of several types of cancer. However, the expression pattern and prognostic value of CDH11 in gastric cancer (GC) have not been reported. In the present study, the expression of CDH11 in patients with GC and its effect on their survival were analyzed using public cancer databases. The expression of CDH11 in GC tissues was significantly higher compared with that in normal gastric tissues. The expression of CDH11 was higher in advanced GC compared with early GC, and increased CDH11 was associated with tumor progression and poor prognosis in patients with GC. The high level of methylation in the promoter of CDH11 in GC tissues was not sufficient to reverse the upregulation of CDH11 caused by transcriptional activation. Finally, the expression pattern and prognostic significance of CDH11 in GC were validated using data from patients with GC recruited for the present study. Collectively, the present results demonstrated that CDH11 was upregulated in GC tissues, and suggested that high CDH11 expression may be associated with progression and poor prognosis in GC.

Nucleolin-Sle A Glycoforms as E-Selectin Ligands and Potentially Targetable Biomarkers at the Cell Surface of Gastric Cancer Cells.

Background: Gastric cancer (GC) is a major health burden worldwide, with half of patients developing metastases within 5 years after treatment, urging novel biomarkers for diagnosis and efficient therapeutic targeting. Sialyl-Lewis A (SLeA), a terminal glycoepitope of glycoproteins and glycolipids, offers tremendous potential towards this objective. It is rarely expressed in healthy tissues and blood cells, while it is present in highly metastatic cell lines and metastases. SLeA is also involved in E-selectin mediated metastasis, making it an ideal target to control disease dissemination. Methods and Results: To improve cancer specificity, we have explored the SLeA-glycoproteome of six GC cell models, with emphasis on glycoproteins showing affinity for E-selectin. A novel bioinformatics-assisted algorithm identified nucleolin (NCL), a nuclear protein, as a potential targetable biomarker potentially involved in metastasis. Several immunoassays, including Western blot and in situ proximity ligation reinforced the existence of cell surface NCL-SLeA glycoforms in GC. The NCL-SLeA glycophenotype was associated with decreased survival and was not reflected in relevant healthy tissues. Conclusions: NCL-SLeA is a biomarker of poor prognosis in GC holding potential for precise cancer targeting. This is the first report describing SLeA in preferentially nuclear protein, setting a new paradigm for cancer biomarkers discovery and targeted therapies.

KLF5 promotes proliferation in gastric cancer via regulating p21 and CDK4.

This study aims to investigate the expression characteristics of Krüppel-like factor 5 (KLF5) in gastric cancer (GC) and its potential correlation to pathological indexes in GC patients. Molecular mechanisms underlying the regulatory effect of KLF5 on GC progression are explored. KLF5 expressions in GC tissues were analyzed through GEPIA dataset and those collected in our hospital. By analyzing the clinical data of GC patients, the correlation between KLF5 level and pathological characteristics of GC was determined. The regulatory effects of KLF5 on proliferative ability and cell cycle progression of SGC7901 and MGC803 cells were assessed by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry. The regulation of KLF5 on expression levels of p21 and CDK4 in GC cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. KLF5 was markedly upregulated in GC tissues. KLF5 level was positively correlated to TNM staging, tumor size, and metastasis of GC. Meanwhile, high level of KLF5 predicted poor prognosis in GC patients. The knockdown of KLF5 in SGC7901 and MGC803 cells attenuated proliferative ability and arrested cell cycle in G0/G1 phase. Both mRNA and the protein levels of p21 were upregulated, and CDK4 levels were downregulated in SGC7901 and MGC803 cells transfected with si-KLF5. KLF5 is upregulated in GC and closely linked to pathological characteristics of GC patients. High level of KLF5 indicates poor prognosis of GC. It is believed that KLF5 may be a potential therapeutic target for GC.

Exosome-Delivered c-Met siRNA Could Reverse Chemoresistance to Cisplatin in Gastric Cancer.

BackgroundDrug resistance often occurs in the treatment of gastric cancer, which is the main cause of poor prognosis of chemotherapy. c-Met is overexpressed in a variety of tumors including gastric cancer, often leads to poor prognosis of gastric cancer, therefore regarded as a key target for the treatment of gastric cancer. This study aims to determine whether exosomes with si-c-Met could inhibit the resistance to cisplatin in gastric cancer (GC).MethodsThe protein expression levels of c-Met in tumor tissues and normal tissues of patients were evaluated by Western blot (WB) and immunohistochemistry (IHC), HEK293T cells were transfected with si-c-Met, exosomes were isolated, then co-cultured with gastric cancer cell lines and confirmed that it was incorporated into the cells by transmitted electron microscopy. Functional experiments were performed to examine the inhibitory effect of exo-si-c-Met on gastric cancer cell resistance in vitro, and xenograft models were used to reveal that exo-si-c-Met can enhance the sensitivity of tumors to cisplatin in vivo.ResultsHigh expression of c-Met is associated with poor prognosis of GC patients. si-c-Met significantly inhibited migration, invasion and promoted apoptosis in vitro, which indicated that si-c-Met sensitizes the response of gastric cancer cells to cisplatin. Exo-si-c-Met sharply reduced c-Met expression in gastric cancer cells and reverse the resistance to cisplatin in vitro and in vivo.ConclusionOur results indicate that exo-si-c-Met can inhibit the invasion and migration of gastric cancer cells and promote apoptosis in vitro and inhibit tumor growth in vivo, reversing the resistance to cisplatin in gastric cancer.

PFND1 Predicts Poor Prognosis of Gastric Cancer and Promotes Cell Metastasis by Activating the Wnt/β-Catenin Pathway.

BackgroundPrefoldin (PFDN) subunits have recently been found to function importantly in various tumor types, while the role of PFDN subunit 1 (PFDN1) in gastric cancer (GC) remains largely unknown. Herein, we aimed to investigate the clinical significance, the biological role and the underlying mechanism of PFDN1 in GC development.Materials and MethodsPFDN1 expression levels were measured in human GC specimens by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Furthermore, the effects of aberrant PFDN1 expression on GC cells behavior were assessed by wound-healing assay and transwell assay in vitro, and metastasis assay in nude mice, as well as Wnt/β-catenin signaling-induced epithelial–mesenchymal transition (EMT)-related markers by qRT-PCR and Western blot.ResultsPFDN1 levels were significantly upregulated in GC tissues compared with those in matched adjacent normal tissues. PFDN1 upregulation correlated strongly with clinical metastasis and unfavorable prognosis for GC patients. In vitro and in vivo studies revealed that PFDN1 facilitated GC cell migration, invasion and metastasis. Mechanically, PFDN1 modulated GC cell behavior by activating Wnt/β-catenin signaling-mediated EMT.ConclusionThese results suggested a central role of PFDN1 in GC metastatic development via the Wnt/β-catenin pathway, thus providing a potential therapeutic target for patients with GC.

Overexpression of COX-2 and clinicopathological features of gastric cancer: a meta-analysis.

BackgroundTo evaluate the correlation between COX-2 overexpression and clinicopathological features of gastric cancer, thus providing theoretical basis for anti-COX-2 targeted therapy.MethodsThe literature about COX-2 expression and gastric cancer was searched in PubMed, Wangfang, VIP, CNKI from the inception to September 2019, with “gastric cancer”, “COX-2”, “cyclooxygenase” as keywords. Stata 15.0 was used to analyze. Age, gender, differentiation, infiltration depth, lymph node metastasis, tumor size, TNM staging were analyzed by OR (95% CI).ResultsNine studies involving 1,289 patients with gastric cancer were identified, among which 878 cases existed COX-2 overexpression. COX-2 overexpression was related to the infiltration depth (OR=1.76; 95% CI: 1.01–1.306; P<0.01) and lymph node metastasis (OR=3.08; 95% CI: 1.64–5.79; P<0.01). While, it was not related to age, gender, differentiation and tumor size.ConclusionsCOX-2 overexpression is valuable in predicting infiltration depth and lymph node metastasis, and could be a predictor of poor prognosis in gastric cancer. COX-2-targeted therapy can be considered as one of the comprehensive treatments for gastric cancer.

High expression of Nucleobindin‐2 is associated with poor prognosis in gastric cancer

Nucleobindin‐2 (NUCB2) is a 396‐amino acid protein, cleaved into the N‐terminal nesfatin‐11–82, nesfatin‐285–163 and the C‐terminal nesfatin‐3166–396. NUCB2 contains a signal peptide, a leucine zipper structure, two Ca2+ binding EF‐hand domains, and has a wide variety of basic cellular functions. NUCB2 is also a precursor protein of nesfatin‐1, which was originally identified in hypothalamic nuclei, and which is a regulatory factor involved in the central control of food intake and energy balance.There are several reports indicating that NUCB2 is also expressed in various human peripheral tissues. Moreover, recent studies have reported that high levels of NUCB2 mRNA and protein are a potent prognostic factor for prostate cancer, endometrial carcinoma, and breast cancer. However, the clinicopathological significance of NUCB2 expression in gastric cancer has still not been elucidated. Therefore, we examined NUCB2 expression in a large number of gastric cancer patients, using immunohistochemistry, to explore its clinicopathological significance. To explore this, we aimed to investigate the NUCB2 expression in gastric cancer tissues and adjacent non‐tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemistry analysis. In our study, NUCB2 level in gastric cancer tissues was higher than in non‐tumor tissues. A high expression of NUCB2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and clinical stage. Furthermore, the expression level of NUCB2 protein was independent predictor of progression‐free survival.In summary, NUCB2 might play a crucial role in gastric cancer development and could serve as an independent predictor of prognosis of gastric cancer patients.Progression‐free survival and overall survival curves of 328 gastric cancer patients divided into two groups according to NUCB2 expression levels. The significant differences were given as p = 0.0214 for progression‐free survival and p=0.0211 for overall survival.Figure 1

Prognostic impact of p53 and/or NY-ESO-1 autoantibody induction in patients with gastroenterological cancers.

Background and AimWe evaluated the clinicopathological and prognostic significance of serum p53 (s‐p53‐Abs) and serum NY‐ESO‐1 autoantibodies (s‐NY‐ESO‐1‐Abs) in esophageal squamous cell carcinoma (ESCC), gastric cancer and hepatocellular carcinoma (HCC).Patients and MethodsA total of 377 patients, 85 patients with ESCC, 248 patients with gastric cancer, and 44 patients with HCC were enrolled to measure s‐p53‐Abs and s‐NY‐ESO‐1‐Abs titers by the enzyme‐linked immunosorbent assay before treatment. The clinicopathological significance and prognostic impact of the presence of autoantibodies were evaluated. Expression data based on the Cancer Genome Atlas and the prognostic impact of gene expression was also examined for discussion.ResultsThe positive rates of s‐p53‐Abs were 32.9% in ESCC, 15% in gastric cancer, and 4.5% in HCC. The positive rates of s‐NY‐ESO‐1‐Abs were 29.4% in ESCC, 9.7% in gastric cancer, and 13.6% in HCC. The presence of s‐p53‐Abs was not associated with tumor progression in these three cancer types. On the other hand, the presence of s‐NY‐ESO‐1‐Abs was significantly associated with tumor progression in ESCC and gastric cancer. The presence of s‐p53‐Abs and/or s‐NY‐ESO‐1‐Abs was significantly associated with poor prognosis in gastric cancer but not in ESCC nor HCC.ConclusionsThe presence of s‐p53‐Abs and/or s‐NY‐ESO‐1‐Abs was associated with tumor progression in ESCC and gastric cancer. These autoantibodies might have poor prognostic impacts on gastric cancer (UMIN000014530).