Negative Gastric Cancer Research Articles

EBV down-regulates COX-2 expression via TRAF2 and ERK signal pathway in EBV-associated gastric cancer

Epstein-Barr virus-associated gastric cancer (EBVaGC) accounts for nearly 10% of gastric cancer. Cyclooxygenase-2 (COX-2) plays a crucial role in cancer progression. However, there is no experimental study on the regulation mechanism of EBV on COX-2 in EBVaGC. To understand more about the tumorigenic mechanism of EBVaGC, the study investigated the role of EBV encode latent membrane protein LMP1 and LMP2A in the regulation of COX-2. The expression of COX-2 was examined in EBVaGC and EBV negative gastric cancer (EBVnGC) cell lines. The plasmids were transfected in SGC7901 to overexpress LMP1/2A. Small interfering RNA (si-RNA) targeting LMP1/2A in GT38 and targeting TRAF2 in SGC7901 were used to detect the expression of COX-2. Furthermore, si-ERK1/2 and the MEK inhibitor PD0325901 were used to investigate whether p-ERK participate in the regulation of COX-2 in SGC7901. The overexpression of LMP1 or LMP2A in SGC7901 down-regulates both COX-2 and TRAF2 expression, and knockdown of LMP1 or LMP2A in GT38 resulted in a certain recovery of COX-2 and TRAF2 expression. Moreover, si-TRAF2 indicated that a sharp down-regulation of COX-2. And the decrease of p-ERK also mediates the inhibitory effect of LMP1 on COX-2. In summary, overexpression of LMP1 and LMP2A inhibits COX-2, which is mediated by a decrease of TRAF2, and p-ERK is involved in the inhibition of COX-2 by LMP1 in gastric cancer.

The Role of Human Epidermal Growth Factor Receptor (HER2/neu) in the Prognosis of Patients with Gastric Cancer.

Objective:Gastric cancer is one of the oncological challenges, and tendency toward target therapy in this cancer has been increased. Controversy still exists on prognostic value of HER2/neu expression and its relationship with clinicopathological characteristics and survival of gastric cancer patients. In this regard, the present study examined the status of HER2/neu in patients with gastric cancer and its prognostic effects.Methods:Pathological samples of 97 gastric cancer patients diagnosed over the last 8 or 9 years (from 2008 to the end of 2017) and treated with 5-fluorouracil, Docetaxel, and Cisplatin (TCF) were studied in this investigation. Patients were assigned to two groups according to their HER2/neu status. First group included patients with positive HER2/neu (Score 3) and second group involved patients with negative HER2/neu (Score 0 and 1). Patients were compared in terms of disease stage, survival rate, and mortality.Results:The mean age of patients was 58 years old. There were 75 men and 22 women in this study. In terms of disease stage, 4, 21, 41, and 31 patients were in stage I, II, III, and IV, respectively. Using IHC method, it was found that 27, 23, 25, and 22 patients had HER2/neu expression with score 0, score +1, score 2+ and score+3, respectively. We discovered that expression of positive HER2/neu was associated with male sex. We also observed that survival and mortality rates following treatment initiation were significantly different between HER2/neu positive and negative gastric cancer patients (P<0.01). Conclusion:Evaluation of HER2/neu status in gastric cancer patients showed that HER2/neu 3+ expression could reduce the patients’ survival. Therefore, it is recommended that patients who may benefit from trastuzumab, be treated. A clinical multi-center trial should be also considered for use of this drug in adjuvant cases.

Tumor microenvironment immune types in gastric cancer are associated with mismatch repair however, not HER2 status.

The treatment of patients with human epidermal growth factor receptor 2 (HER2)-negative gastric cancer is a major challenge. Immunotherapy using immune checkpoint inhibitors is a rapidly growing field. In a number of malignancy types it has been demonstrated that patients with mismatch repair deficiency efficiently respond to programmed death-ligand 1 (PD-L1) blockade therapy. Recent studies have evaluated tumor microenvironment immune types to predict which patients may clinically benefit from immunotherapy. The present study aimed to evaluate the immunohistochemical expression of PD-L1 in 70 gastric cancer tissue samples. Potential associations between PD-L1 expression and mismatch repair deficiency, HER2 and Epstein Barr virus (EBV) status were then investigated in the context of the tumor microenvironment. A positive association was identified for PD-L1 expression with mismatch repair deficiency and EBV status; however, no association was revealed with HER2 status. Immunohistochemistry was then used to classify the microenvironment immune types. This demonstrated that the majority of the gastric cancer samples (73%) belonged to the tumor microenvironment immune type II [PD-L1−/cluster of differentiation 8 (CD8)+ low], which involves an immune ignorant state and has a low sensitivity to immunotherapy. However, 7% of the gastric cancer cases were identified to belong to the tumor microenvironment immune type I (PD-L1+/CD8+ high), which exhibits adaptive immune escape responses and a high chance of reversion with immune checkpoint blockade therapy. In conclusion, the present study emphasized the importance of evaluating tumor microenvironment immune types, mismatch repair deficiency status and EBV status, rather than PD-L1 expression alone, when evaluating the eligibility of a patient for immunotherapy with anti-programmed cell death protein-1/PD-L1 antibodies.

Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer.

Exosomal transfer of oncogenic miRNAs can enhance recipient cell growth, metastasis and chemoresistance. Currently we found that microRNA-501-5p (miR-501) was overexpressed in doxorubicin-resistant gastric cancer (GC) SGC7901/ADR cell-secreted exosomes (ADR Exo) than that in SGC7901 cell-secreted exosomes (7901 Exo). ADR Exo was internalized by SGC7901, and a Cy3-miR-501 mimic was transferred from SGC7901/ADR to SGC7901 via exosomes. ADR Exo conferred doxorubicin resistance, proliferation, migration and invasion abilities to negative control miRNA inhibitor-expressing GC cells, whereas it inhibited apoptosis. MiR-501 knockdown or BH3-like motif-containing protein, cell death inducer (BLID) overexpression could reverse the effects of ADR Exo on recipient cells. SGC7901 cells cocultured with SGC7901/ADR prior to treatment with GW4869 or transfection of a miR-501 inhibitor were sensitive to doxorubicin and exhibited attenuated proliferation, migration and invasion and increased apoptosis. The intratumoral injection of ADR Exo into negative control miRNA inhibitor-expressing SGC7901 cells induced rapid subcutaneous tumor growth and resistance to doxorubicin compared to that of miR-501 knockdown or BLID-overexpressing cells. This effect is possibly achieved by exosomal miR-501-induced downregulation of BLID, subsequent inactivation of caspase-9/-3 and phosphorylation of Akt. Exosomal miR-501 might be a therapeutic target for GC.

Mo1358 CLINICOPATHOLOGIC AND ENDOSCOPIC FEATURES OF HELICOBACTER PYLORI NEGATIVE EARLY GASTRIC CANCER TREATED BY ENDOSCOPIC SUBMUCOSAL DISSECTION

Helicobacter pylori negative gastric cancer (HpNGC) is a rare disease of less than 5%, and its clinical features are not well known. Early gastric cancer usually develops according to the Correa’s hypothesis, therefore, Helicobacter pylori negative early gastric cancer is less common. The aim of this study was to evaluate the endoscopic and pathologic features of Helicobacter pylori negative early gastric cancer treated by endoscopic resection.

Development and validation of a new staging system for node-negative gastric cancer based on recursive partitioning analysis: An international multi-institutional study.

BackgroundWhether the tumor‐node‐metastasis (TNM) staging system is appropriate for patients with node‐negative gastric cancer (GC) is still inconclusive. The modified staging system developed by recursive partitioning analysis (RPA) showed good prognostic performance in a variety of cancers. The application of RPA has not been reported in the prognostic prediction of GC.MethodsNode‐negative GC patients who underwent radical resection at Fujian Medical University Union Hospital (n = 862) and Sun Yat‐sen University Cancer Center (n = 311) with at least 5 years of follow‐up were selected as the training set. RPA was used to develop a modified staging system. Patients from the Surveillance, Epidemiology, and End Results database (n = 1415) were selected as the validation set.ResultsThe 5‐year overall survival (OS) rates of patients with 8th AJCC‐TNM stage IA‐IIIA in the training set were IA 95.2%, IB 87.1%, IIA 78.3%, IIB 75.8%, and IIIA 72.6%. Multivariate analysis (MVA) showed that larger tumor size, elder age, and deeper depth of invasion were independent predictors for OS in patients with node‐negative GC (all P < 0.05). Patients were reclassified into RPA I, RPA II, RPA III, and RPA IV stages based on RPA; the 5‐year OS rates were 96.1%, 87.2%, 81.0%, and 64.3%, respectively, with significant difference (P < 0.05). Two‐step MVA showed that the RPA staging system was an independent predictor of OS (P < 0.05). Compared with the 8th AJCC‐TNM staging system, the RPA staging system had a smaller AIC value (2544.9 vs 2576.2), higher χ2 score (104.2 vs 69.6) and higher Harrell's C‐index (0.697 vs 0.669, P = 0.007). The similar results were found in the validation set.ConclusionsA new prognostic predictive system based on RPA was successfully developed and validated, which may be suggested for staging node‐negative GC in future.

TP53 Promoter Methylation in EBV-Positive and EBV - Negative Gastric Cancer - A Pilot Study

Gastric cancer is a very important problem in public health worldwide. Gastric Cancer (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related mortality worldwide [1].

Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial

BackgroundPlatinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4–6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment.MethodsThis is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis.DiscussionThe ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression.Trial registrationARMANI is registered at ClinicalTrials.gov (NCT02934464, October 17, 2016) and EudraCT(2016–001783-12, April 202,016).

Tumor Size Improves the Accuracy of the Prognostic Prediction of Lymph Node–Negative Gastric Cancer

BackgroundTumor size has been regarded as the “T” stage of many solid tumors because of its effect on prognosis. However, the prognostic impact of tumor size in gastric cancer (GC) is still controversial. Materials and methodsA total of 436 patients with curatively resected GC and those without lymph node metastasis in our center were retrospectively enrolled. The appropriate cutoff points for tumor size were determined. Potential prognostic factors were analyzed. In addition, a pathological tumor-size (pTS) classification system was proposed to evaluate the superiority of its prognostic prediction of node-negative GC patients compared with that of the pT staging system. ResultsThe ideal cutoff points for tumor size were 4 and 8 cm. In the multivariate analysis, tumor size was identified as an independent prognostic factor for node-negative GC patients after surgery, as was pT stage. The pTS classification was found to be more appropriate for predicting the overall survival of node-negative GC patients after curative surgery than pT stage, and the −2 log-likelihood of the pTS classification (1680.782) was smaller than the value of pT (1695.239). ConclusionsAs an independent prognostic factor, tumor size should be incorporated into the pT staging system to enhance the accuracy of the prognostic prediction of node-negative GC patients.

The Prognostic and Predictive Value of microRNAs in Patients with H. pylori-positive Gastric Cancer.

Gastric cancer (GC) has a high mortality rate with a poor 5-year survival. Helicobacter pylori (H. pylori) is present as part of the normal flora of stomach. It is found in the gastric mucosa of more than half of the world population. This bacterium is involved in developing H. pylori-induced GC due to the regulation of different micro ribonucleic acid (miRNA or miR). miRNAs are small noncoding RNAs and are recognized as prognostic biomarkers for GC that may control gene expression. miRNAs may function as tumor suppressors, or oncogenes. In this review, we evaluated studies that investigated the ectopic expression of miRNAs in the prognosis of H. pylori positive and negative GC.

Abstract P6-20-16: BAT8003, a potent anti-Trop-2 antibody-drug conjugate, for the treatment of triple negative breast cancer

Abstract Trophoblast cell surface antigen 2 (Trop-2) is overexpressed on many epithelial carcinomas, yet is expressed at much lower level on normal tissue. Overexpression of Trop-2 has been correlated with poor prognosis in several solid tumors. These two characteristics make Trop-2 a potential drug target. An antibody-drug conjugate (ADC) targeting Trop-2, IMMU-132, has recently been demonstrated to be effective in treating triple negative breast cancer (TNBC) and gastric cancer patients. Here we present a Trop-2 ADC, BAT8003, which contains an uncleavable linker and a maytansine derivative as the payload. An A114C mutation on antibody heavy chain was introduced to BAT8003 for site-specific conjugation, in order to generate a more homogeneous product for a better pharmacokinetics profile. BAT8003 is also completely devoid of fucose modification, to allow for enhanced ADCC effect. We show that BAT8003 is effectively internalized upon binding to Trop-2, and inhibits proliferation of Trop2-overexpressed tumor cells with IC50s of ˜1 nM. In a TNBC (MDA-MB-468 cell) mouse xenograft model, BAT8003 strongly inhibits tumor growth at a dose level as low as 5 mg/kg. BAT8003 also demonstrates potent activity in another TNBC (MX-1 cell) mouse tumor model, in which it shows the same inhibition activity as the naked antibody conjugated heterogeneously with almost two fold payload (DAR 3.5), suggesting the effect caused by site-specific conjugation. We are currently developing BAT8003 for clinical evaluation in TNBC and other cancer indications. Citation Format: Tang W, Huang X, Ou Z, Yan H, Gan J, Dong Q, Tan B, Yang Y, Guo Y, Li S, Thomas B, Yu J-C. BAT8003, a potent anti-Trop-2 antibody-drug conjugate, for the treatment of triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-20-16.

Methylation of Epstein-Barr Virus-Associated Gastric Cancer Suppressor Genes

Objective: To identify the methylation silenced tumor suppressor genes in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC). Methods: EBV-positive (GT38, PT and SNU719) and negative (SGC7901) gastric cancer cell lines were selected and treated with 5-Aza-CdR. Then real-time fluorescence quantitative PCR was used to validate the results of microarray, and methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) were adopted to detect the CpG island methylation levels of gene promoters. Results: The expression levels of 6 differentially expressed genes (H19, LOXL1, ARMCX2, LXN, CDH3 and MMP7) before and after 5-Aza-CdR treatment were confirmed by real-time qPCR, which are consistent with the results of microarray analysis. There were different degrees of methylation in LOXL1 gene promoter in EBVaGC. GT38 and PT were fully methylated, and SGC7901 and HGC-27 was unmethylated, suggesting that this gene is a candidate methylation silenced tumor suppressor gene. The methylation rate of LOXL1 in EBVaGC was significantly higher than that in EBV-negative gastric cancer (EBVnGC). Conclusion: The promoter region of candidate tumor suppressor gene LOXL1 shows high methylation status, indicating that EBV critically accounts for the methylation of LOXL1 gene regulatory region. EBV is involved in the pathogensis of EBVaGC that aberrant methylation occurred in promoter CpG island, which inactivates tumor suppressor genes.

NNMT Regulates Cancer Immunity and Is a Potential Prognostic Biomarker in Gastric and Colorectal Cancers

Background: Nicotinamide N-methyltransferase (NNMT), a cytosolic enzyme that catalyzes the N-methylation of nicotinamide, has been shown to be critical for promoting cancer progression, but little is known its role in gastric and colorectal cancers. Methods: We explored the role of NNMT in predicting prognosis and immune infiltration of gastric and colorectal cancers. Data was obtained from RNAseq Atlas, Oncomine, tumor Immune Estimation Resource (TIMER) databases, Kaplan-Meier plotter, PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). Findings: NNMT is overexpressed in gastric and colorectal cancers compared to adjacent normal tissues. High NNMT expression was significantly associated with worse outcome in gastric and colorectal cancer patients. However, high expression of NNMT was highly predictive of effectual 5-fluorouracil (5-FU) treatment in HER2 negative gastric cancer patients. Furthermore, there were significant positive correlations between NNMT expression and immune cells infiltration in gastric and colorectal cancers. Conversely, NNMT did not exert any significant effect on prognosis and immune infiltration in lung cancer. Interpretation: NNMT could be a prognostic factor for predicting clinical outcomes and immune infiltration, as well as a molecular target for the treatment of gastric and colorectal cancers. Funding: This work was supported in part by funding from the National Natural Science Foundation of China (No. 81502598). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: Not required.

MiR-126: An indicator of poor prognosis and recurrence in histologically lymph node-negative gastric cancer.

Few biomarkers are available for the prediction of prognosis and recurrence in lymph node (LN)-negative gastric cancer (GC) currently. miR-126 functions as a tumor suppressor in GC, however, its clinical significance in LN-negative GC remains unknown. To investigate the associations of tissue miR-126 level with the clinicopathological characteristics and clinical outcome of LN-negative GC patients. Quantitative real-time polymerase chain reaction was performed to examine the tissue miR-126 level in 315 LN-negative GC patients who underwent curative gastrectomy with D2 lymphadenectomy. The associations of tissue miR-126 level with clinicopathological characteristics and clinical outcome were evaluated. Compared with matched adjacent non-tumor tissues, miR-126 expression was significantly down-regulated in tumor tissues. A reduced tissue miR-126 level statistically correlated with aggressive clinicopathological characteristics, including larger tumor size, deeper local invasion, and poorer prognosis. Notably, multivariate analysis identified advanced T stage and low miR-126 level as independent predictors of the unfavorable prognosis and recurrence of LN-negative GC. These results indicate for the first time that advanced T stage and low miR-126 level are predictors of unfavorable prognosis and recurrence in LN-negative GC patients. These parameters should be taken into account to stratify patients for adjuvant therapy and close follow-up.

Transduced caudal-type homeobox (CDX) 2/CDX1 can induce growth inhibition on CDX-deficient gastric cancer by rapid intestinal differentiation.

Intestinal metaplasia induced by ectopic expression of caudal‐type homeobox (CDX)2 and/or CDX1 (CDX) is frequently observed around gastric cancer (GC). Abnormal expression of CDX is also observed in GC and suggests that inappropriate gastrointestinal differentiation plays essential roles in gastric tumorigenesis, but their roles on tumorigenesis remain unelucidated. Publicly available databases show that GC patients with higher CDX expression have significantly better clinical outcomes. We introduced CDX2 and CDX1 genes separately into GC‐originated MKN7 and TMK1 cells deficient in CDX. Marked suppression of cell growth and dramatic morphological change into spindle‐shaped flat form were observed along with induction of intestinal marker genes. G0‐G1 growth arrest was accompanied by changed expression of cell cycle‐related genes but not with apoptosis or senescence. Microarray analyses additionally showed decreased expression of gastric marker genes and increased expression of stemness‐associated genes. Hierarchical clustering of 111 GC tissues and 21 non‐cancerous gastric tissues by selected 18 signature genes based on our transcriptome analyses clearly categorized the 132 tissues into non‐cancer, “CDX signature”‐positive GC, and “CDX signature”‐negative GC. Gene set enrichment analysis indicated that “CDX signature”‐positive GC has lower malignant features. Immunohistochemistry of 89 GC specimens showed that 50.6% were CDX2‐deficient, 66.3% were CDX1‐deficient, and 44.9% were concomitant CDX2/CDX1‐deficient, suggesting that potentially targetable GC cases by induced intestinal differentiation are quite common. In conclusion, exogenous expression of CDX2/CDX1 can lead to efficient growth inhibition of CDX‐deficient GC cells. It is based on rapidly induced intestinal differentiation, which may be a future therapeutic strategy.

Prevention of Stomach Carcinoma Spread by Induces Bioenergetic Dysfunction in UCP2-Negative Gastric Cancer Cells with Hydrogen Sulfide

Background: Metabolite profiling stratifies gastric cancer (GC) cells into subtypes with distinct sensitivities to metabolic inhibitors. Hydrogen sulfide (H2S), an obvious characteristic is selectively suppressing cancer spread. However, it intrigues broad interest to explore the clinical benefits of cancer therapy, with the current understanding of molecular mechanisms of H2S which remains unknown. Methods: Transcriptome analysis identified that H2S inhibited uncoupling protein 2 (UCP2)-negative GC cells spread in cells cultures and animal models. The levels of bioenergetic function and proton leak was assayed by real-time bioenergetic analyzer. Metabolomics profiling revealed that H2S disturbed palmitic acid beta-oxidation to inhibitory of mitochondrial ATP (mitoATP) synthesis. Liquid chromatograph-mass spectrometer (LC-MS) and Chromatin Immunoprecipitation (ChIP) evaluated H2S promoted POZ/BTB family protein-33 (ZBTB33) nuclear translocation. Results: H2S promotes ZBTB33 nuclear translocation, and up-regulates UCP2 expression at the level of gene and protein in UCP2-negative GC cells. H2S triggers proton leak and turn off the metabolic switch that is essential for GC spread. Functional analysis showed repressed mitoATP synthesis, correlated negatively with ROS-mTOR signaling pathway, activated Casp8, and induced cell death in UCP2-negative GC cells following overexpression of UCP2. H2S reinforces that UCP2 catalyzes respiratory chain uncoupling by an H -assisted mechanism. Interpretation: Our preclinical work showed UCP2-negative GC cells into subtypes with distinct sensitivities to lipid inhibitor in drug discovery for screening chemopreventive agents against GC. We additionally demonstrate that the expression of UCP2 in GC served as a prognostic biomarker and negatively correlated with recurrence of de novo GC after curative treatment. Funding Statement: This work was supported by the Strategic Priority Research Program of the Science and Technology Commission of Shanghai (1312JC1408402 for Zhirong Wang). Declaration of Interests: No potential conflicts of interest were disclosed. Ethics Approval Statement: This animal study was conducted in accordance with the rules and regulations of the Institutional Animal Care and Use Committee (IACUC) at the Department of Laboratory Animal Science, Fudan University (Shanghai, P.R. China). Informed consent was approved by the Ethics Committees of Tongji Hospital and all subjects gave written informed consent.

Expression and significance of lysine-specific histone demethylase 2B in gastric cancer

Objective To study the expression and significance of lysine-specific histone demethylase 2B (KDM2B) protein in gastric cancer and its correlation with clinicopathologic features and prognosis for gastric cancer. Methods The expression of KDM2B protein was detected by the immunohistochemical staining. The relationship between the expression of KDM2B and clinicopathologic characteristics in gastric cancer was analyzed by χ2 test and survival analyses were done by the Kaplan-Meier method and Cox regression, and the differences between the curves were tested with the two-tailed log-rank test. Results The positive rate of KDM2B protein was 58.9% in 236 cases of gastric cancer, and 11.4% in the adjacent gastric mucosa (χ2=25.690, P=0.000). The positive rate of KDM2B was correlated with histological classification, lymph node status, TNM stage and human epidermal growth factor receptor-2 (Her-2) expression (χ2=12.922, 6.817, 15.089, 5.143, P=0.002, 0.033, 0.001, 0.023, respectively). The Kaplan-Meier analysis showed KDM2B was associated with poor prognosis [hazard ratio (HR)=2.340, P=0.000]. The 5-year survival rate of KDM2B positive gastric cancer was 22.3%, and the median survival time was 19 months. The 5-year survival rate of KDM2B negative gastric cancer was 49.5%, and the median survival time was 55 months. Furthermore, Cox stepwise hazard analysis revealed KDM2B was an independent prognostic index for gastric cancer. Conclusion KDM2B was an independent prognostic index for gastric cancer. Key words: Gastric cancer; Lysine-specific histone demethylase 2B; Prognosis; Immunohistochemistry

Clinichopathological and Endoscopic Features of Helicobacter pylori—Negative Early Gastric Cancer

Clinichopathological and Endoscopic Features of Helicobacter pylori—Negative Early Gastric Cancer

ISY8-4 - Clinical guideline for gastrointestinal cancers in Korea with focusing on metastatic gastric cancer

Korean guideline on the diagnosis and treatment of gastric cancer (GC) was published in Korean language in 2012. It will be revised this year (2018) with updating recent publications. Generally, metastatic or unresectable GC is treated in Korea as follows. In metastatic or unresectable GC, doublets of fluoropyrimidine plus platinum are the standard of care as first¯line chemotherapy in HER2 negative GC, while trastuzumab in combination with capecitabine/5¯FU and cisplatin is the standard of care in HER2 positive GC. HER2 positivity is defined as either HER2 immunohistochemistry (IHC) 3 positive or HER2 IHC 2 positive and positive in situ hybridization. Taxane containing triplet regimens are not considered standard of care, however, they can be tried for conversion surgery with reduction of tumor burden in selected patients. In second¯line setting, there are several options, which include taxaneş irinotecan, weekly paclitaxel plus ramucirumab, and ramucirumab alone. Either docetaxel or paclitaxel (both weekly and 3¯weekly) can be used as one of the standard second¯line chemotherapeutic agents. Among these,weekly paclitaxel plus ramucirumab is more favored, if patientś condition is appropriate to receive the combination chemotherapy. In third line setting, taxanes or irinotecan can be used if those chemotherapeutic agents were not used previously. In a phase 3 trial, nivolumab has been proven to be superior to placebo with more long term survivors as a third or later¯line treatment in GC. Recently, nivolumab has been approved in Korea, and it is currently used as a third or later¯line treatment.

Epstein-Barr virus infection associated with pepsinogens and Helicobacter pylori infection in patients with gastric cancer

BackgroundThere is no study reporting the influence of the Epstein-Barr virus (EBV) infection on the biomarkers of gastric function like pepsinogen (PG) I and II in patients with gastric cancer, and the relationship between the infection of EBV and Helicobacter pylori (HP) is unclear. This study focused on these issues. MethodsIn this study, we detected the serum levels of PGI, PGII, anti-HP (immunoglobulin G) IgG antibodies and EBV DNA load in a total of 189 gastric cancer patients confirmed to be EBV positive or negative in tissue using in situ hybridization of EBV-encoded small RNAs (EBERs). ResultsCompared to 123 EBV negative gastric cancer patients, the 66 patients infected with EBV exhibited significant higher levels of PGI and PGI/II ratio and meanwhile, had remarkably lower levels of anti-HP IgG. The prevalence of HP infection in EBV positive patients was 13.6%, and 52.8% in EBV negative patients. In subsequent analysis concerning the EBV DNA load, the patients were divided into two groups by a cutoff value of 1000 copies/ml. The EBV DNA load showed highly consistent association with PGI, PGI/II ratio and HP. ConclusionsEBV infection in situ increased the serum levels of PGI and ratio of PGI/PGII in gastric cancer patients. Moreover, the EBV infection exclusively exists with HP infection in the patients with gastric cancer.