Prognostic Factor In Gastric Cancer Research Articles

Long noncoding RNA FEZF1-AS1 indicates a poor prognosis of gastric cancer and promotes tumorigenesis via activation of Wnt signaling pathway

Long non-coding RNAs (lncRNAs) have been demonstrated that it plays very important role in development and progression of carcinomas. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been proved to be implicated in tumor initiation and progression of various cancers, recently. Nevertheless, the biological function and clinical significance of lncRNA FEZF1-AS1 in gastric cancer (GC) are not clear enough. Here, we concentrated on the association of FEZF1-AS1 expression and clinicopathological factors in GC tissues and cells. Moreover, we explored the potential regulatory mechanisms. The results showed that lncRNA FEZF1-AS1 was observably upregulated in human GC tissues and GC cell lines, compared with the adjacent non-tumor tissues and human gastric epithelial cell line (GES-1). Moreover, high expression of lncRNA FEZF1-AS1 was significantly associated with later stage and higher grade. Furthermore, Kaplan-Meier survival analysis was conducted, indicating that lncRNA FEZF1-AS1 may be an independent prognostic factor in GC. Additionally, the area under the receiver operating characteristic (ROC) curve of lncRNA FEZF1-AS1 exhibited its diagnostic value in GC. Notably, whenever the lncRNA FEZF1-AS1 was silenced, the proliferation of GC cells were significantly inhibited and the cell cycle was arrested at a G0/G1 stage in GC cells. Furthermore, downregulation of lncRNA FEZF1-AS1 could suppress the activation of the Wnt/β-catenin signaling pathway. Conclusively, our findings indicated that lncRNA FEZF1-AS1 could be considered as a novel biomarker for the treatment of GC.

The Prognostic Value of the Prechemotherapy Neutrophil - Lymphocyte Ratio in Gastric Cancer

Background: gastric cancer is the 5th most common cancer worldwide, with about one million newly diagnosed cases annually. It causes one of the highest cancer burdens, as measured by disability-adjusted life years lost. It is the third-leading cause of cancer-related death worldwide, after lung and liver malignancies. It is increasingly recognized that variations within clinical outcomes in cancer patients are influenced by not only the oncological characteristics of the tumor, but also the host-response factors. Aim of the work: this study aimed to investigate the prognostic value of prechemotherapy NLR in the gastric cancer patients and also to assess the association between high NLR and clinicopathological features; e.g. tumor stage, site, gross morphology …etc. Patients and methods: this retrospective study included patients, diagnosed with gastric or gastroesophageal cancer, who presented to Oncology Department in Ain Shams University Hospital from January 2013 till December 2016. 61 patients were included in this study. Results: we found a significant correlation between presence of ascites and high NLR. This relation wasn’t discussed in any previous study as far as we know. There was a significant correlation between NLR and each of the following: - overall survival and event-free survival. This was consistent with the results of previous studies worldwide. Therefore, our study proved that the prechemotherapy NLR is a prognostic factor in gastric cancer. Conclusion: the prechemotherapy NLR was significantly correlated with presence of ascites at diagnosis of gastric cancer. It is an independent prognostic factor in gastric cancer. It affects both event free survival and overall survival.

High expression of eIF3d is associated with poor prognosis in patients with gastric cancer.

BackgroundEukaryotic initiation factor 3 subunit d (eIF3d) is the largest subunit of eIF3, which is shown to promote protein synthesis in cancer cells. Increased expression of eIF3d has been shown in some types of cancers, but has not been previously studied in gastric cancer (GC). Thus, the aim of this study was to analyze eIF3d expression in GC.Patients and methodsExpression of eIF3d was detected by immunohistochemistry in GC tissues and adjacent noncancerous (ANC) tissues. Samples were obtained from 210 patients with GC who had received curative gastrectomy. Clinicopathological features and survival rate were also analyzed.ResultsExpression rates of eIF3d in GC and ANC were 45.2% and 21.0%, respectively. High expression of eIF3d protein was significantly related to tumor stage, as determined by lymph node metastasis and depth of invasion (p<0.05). The Kaplan–Meier survival curves showed that patients with high eIF3d expression had a significantly poor overall survival (p=0.005). Multivariate Cox regression analyses showed that the level of eIF3d was an independent predictive factor of poor prognosis for GC (p=0.017).ConclusionExpression of eIF3d was upregulated in GC. High expression of eIF3d was determined as an independent poor prognostic factor in GC. It is suggested that eIF3d could be a good biomarker in GC.

The expression level of miR-203 in patients with gastric cancer and its clinical significance

BackgroundThe clinical significance of miR-203 and its prognostic value have not been investigated in gastric cancer. MethodsWe assessed miR-203 expression in 141 gastric cancer samples and 141 paired non-cancerous samples by real-time PCR and calculated using the 2−ΔΔCt method. Differences between groups were examined for statistical significance by Student’s t-test. Survival curves were computed by the Kaplan-Meier method, and differences between survival curves were compared by the log rank test. ResultsThe expression of miR-203 was significantly lower in gastric cancer samples compared to non-cancerous samples (P<0.0001). Low miR-203 expression was found to be closely correlated with advanced stage (p=0.005), and lymph node involvement (p=0.009). Kaplan-Meier analysis with the log-rank test indicated that low miR-203 expression had a significant impact on overall survival (39.4% vs. 62.5%; P=0.043) and progression-free survival (32.5% vs. 58.6%; P=0.023). Furthermore, multivariate analysis revealed that miR-203 expression level was independent prognostic factors for overall survival (HR=2.73, 95% CI: 1.69–8.91; P=0.01), as well as progression-free survival (HR=4.19, 95% CI: 2.91–10.12; P=0.005). ConclusionOur data validate an important clinical significance of miR-203 in gastric cancer, and reveal that it might be a potential prognostic factor for gastric cancer. Large- scale and long-term follow-up studies are needed to confirm the significance of miR-203 in gastric cancer.

High level of homeobox A9 and PBX homeobox 3 expression in gastric cancer correlates with poor prognosis.

The homeobox protein homeobox (HOXA9) is a transcriptional factor that regulates patterning during embryogenesis and controls cell differentiation. HOXA9 dysfunction has been implicated in certain cancers. However, the role of HOXA9 in gastric cancer is poorly understood. The present study investigated HOXA9 and its cofactor PBX homeobox 3 (PBX3) expression in patients with gastric cancer. Paired tissue samples from 24 patients and paraffin embedded tissues of gastric cancer patients (104 males and 24 females) were included. HOXA9 and PBX3 expression levels were determined by reverse transcription quantitative polymerase chain reaction in fresh tissues, and by immunohistochemical staining in paraffin embedded tissues. The association between HOXA9/PBX3 expression and clinicopathological features was established. The results demonstrated that HOXA9 and PBX3 mRNA levels were significantly upregulated (P=0.032 for HOXA9 and P=0.031 for PBX3) in gastric cancer tissue. Immunohistochemical staining revealed that HOXA9 expression was associated with differentiation, lymph node metastasis and tumor-node-metastasis (TNM) stage, and PBX3 expression was associated with lymph node metastasis and TNM stage. Correlation analysis revealed a high coincidental expression of HOXA9 and PBX3 levels in gastric cancer (r=0.391; P<0.001). Survival analysis showed that high expression of HOXA9 or PBX3 was associated with poor survival of gastric cancer, and multivariate analysis using Cox's regression model showed that PBX3 expression was an independent prognostic factor in gastric cancer. There was elevated expression of HOXA9 and PBX3 in gastric cancer patients, and high-level expression of those proteins was associated with poor prognosis of gastric cancer. The present study underlines the significance of HOXA9/PBX3 in the development of gastric cancer.

The tumor-stromal ratio as a strong prognosticator for advanced gastric cancer patients: proposal of a new TSNM staging system

BackgroundInsufficient attention is paid to the underlying tumor microenvironment (TME) evolution, that resulting in tumor heterogeneity and driving differences in cancer aggressiveness and treatment outcomes. The morphological evaluation of the proportion of the stroma at the most invasive part of primary tumor (tumor-stromal ratio, TSR) in cancer is gaining momentum as evidence strengthens for the clinical relevance.MethodsTissue samples from the most invasive part of the primary gastric cancer (GC) of 494 patients were analyzed for their TSR, and a new TSNM (tumor-stromal node metastasis) staging system based on patho-biological behaviors was established and assessed.ResultsTSR is a new and strong independent prognostic factor for GC patients. The likelihood of tumor invasion is increased significantly for patients in the stromal-high subgroup compared to those in the stromal-low subgroup (P = 0.011). The discrimination ability of TSR was not less than the TNM staging system and was better in patients with stages I and II GC. We integrated the TSR parameter into the TNM staging system and proposed a new TSNM staging system creatively. There were three new subgroups (IC, IIC, IIID). There were four major groups and 10 subgroups in the TSNM system. The difference in overall survival (OS) was statistically significant among all TSNM system (P < 0.005 for all). Deep analyses revealed well predictive performance of the TSNM (P < 0.001).ConclusionsThis study confirms the TSR as a TME prognostic factor for GC. TSR is a candidate TME parameter that could easily be implemented in routine pathology diagnostics, and the TSNM staging system has been established to optimize risk stratification for GC. The value of the TSNM staging system should be validated in further prospective study.

Prognostic significance of perigastric tumor deposits in patients with primary gastric cancer

BackgroundThe presence and the prognostic significance of perigastric tumor deposits (TDs) in primary gastric cancer have not been extensively studied. The aim of this study was to evaluate the prognostic significance perigastric TDs in primary gastric cancer.MethodsFrom 2005 to 2010, 1250 patients underwent R0 gastrectomy at the Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. Out of 1250 patients, 132 patients with perigastric TDs were identified. Additionally, 132 patients with staged matched gastric cancer without tumor deposits were selected as a control group.ResultsPerigastric TDs were observed in 132 (10.5%) of the 1250 patients with gastric cancer who underwent R0 gastrectomy. There were 94 males (71.21%) and 38 females (28.79%) (2.47:1). The mean age was 57.21 years. Clinicopathologic characteristics between the two groups matched well. There was a significant difference in the overall survival of those with and without TDs by univariate (p<0.05) and multivariate (p < 0.05) survival analysis. The 1-, 3-and 5-year overall survival rates of patients with TDswere69.6%, 39.3%, and 24.2%, respectively, and were significantly poorer than those of the staged matched control group. There was no correlation between the number of TDs and patient survival in patients with gastric cancer (p>0.05); however, when comparing each pT tumor group with the perigastric TD group, the stage T4 survival rate was very similar to that observed in patients with TDs.ConclusionsPerigastric TDs are an independent predictive prognostic factor for gastric cancer and may be appropriately considered a form of serosal invasion. We suggest that TDs should be included in TNM staging system for better outcomes.

Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection.

Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial.We performed in situ hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers. A multiplex polymerase chain reaction with five quasimonomorphic markers was performed for MSI.PD-L1 expression was observed in 123 cases (31.2%), and clinicopathological features such as MET overexpression, high pT stage, and a lack of lymphatic invasion represent significant risk factors associated with PD-L1 overexpression in gastric cancers. No associations of EBV, MSI, or mucin phenotype with PD-L1 expression were statistically significant. PD-L1 expression was a strong indicator for worse overall survival (OS) but borderline significant in disease-free survival (DFS). A combined analysis of PD-L1 and MET expression indicated that the PD-L1+/MET+ subgroup showed the worst prognosis when compared to the PD-L1-/MET- subgroup, which had the best clinical outcome. Furthermore, PD-L1 overexpression exhibited poor prognosis in terms of both OS and DFS in EBV-negative, microsatellite stable, and intestinal mucin phenotype tumors. In conclusion, this is the first study to evaluate the overexpression of MET as a risk factor for PD-L1 positivity in gastric cancer tissue as well as the reliability and prognostic relevance of PD-L1/MET co-expression after surgery.

Abstract 4717: Combination of PD-L1 expression and microsatellite instability status is a useful prognostic factor in gastric cancer

Abstract Interaction of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) induces functional impairment of antigen-specific T cells, which leads to immune evasion of tumors. Immune checkpoint therapy including PD-1/PD-L1 blockade is an emerging treatment strategy which brings great improvement in patient’s prognosis. Microsatellite instability (MSI) is a condition of genomic instability caused by the loss of DNA mismatch repair activity, which has recently received a lot of attention from the standpoint of cancer immunotherapy. While the TNM classification system is commonly used on various malignant tumors for prediction of prognosis and planning of treatment strategy, establishment of prognostic factors related to cancer immune system is considered important as cancer immunotherapy has recently become more and more popular. Thus, we investigated the usefulness of PD-L1 expression and MSI status in addition to histological type as prognostic factors in gastric cancer. In this study, 255 gastric cancer cases which had curative surgical resection at Okayama University Hospital between 2002 and 2009 were analyzed retrospectively. PD-L1 expression level was classified into 4 groups according to PD-L1 positive rate on tumors on immunohistochemical staining (0: &amp;lt; 1%, 1+: 1-5%, 2+: 5-10%, 3+: ≥10%), and 2+ and 3+ were defined as PD-L1 positive. MSI status was analyzed by PCR and classified into MSI-high (MSI-H), and MSI-low and Microsatellite stability (non-MSI). Histological type was divided into intestinal and diffuse according to the Lauren classification.PD-L1 positive rate was 15%, and PD-L1 positive was significantly correlated with advanced stage and invasive status. Overall survival (p=0.0109) and disease-free survival (p=0.0052) were significantly poor in PD-L1 positive group, and a multivariate analysis revealed that PD-L1 expression was an independent risk factor for recurrence after surgery (p=0.0160, odds ratio: 3.19). MSI-H was detected in 7.5%, and more observed in PD-L1 positive cases (p=0.0068). Although non-MSI, as a single factor, showed only a weak tendency to have poor prognosis compared to MSI-H (p=0.1965), combination of PD-L1 positive and non-MSI (PD-L1/non-MSI) showed significantly poor prognosis (p=0.0010). Although other combinations also showed the usefulness in detection of patients with poor prognosis, such as PD-L1 positive and diffuse type, and non-MSI and diffuse type, a multivariate analysis revealed that PD-L1/non-MSI was the most useful combination among them to predict poor prognosis (p=0.0009, hazard ratio: 3.88). In conclusion, while PD-L1 expression is a useful prognostic factor and predictive factor for recurrence after surgery as a single factor, combination with MSI status can be more useful and attractive prognostic factor in gastric cancer. Citation Format: Toshiaki Morihiro, Shinji Kuroda, Nobuhiko Kanaya, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara. Combination of PD-L1 expression and microsatellite instability status is a useful prognostic factor in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4717. doi:10.1158/1538-7445.AM2017-4717

Abstract 4001: Infiltration of neutrophils in the tumor was associated with poor prognosis of patients with gastric cancer

Abstract Background:Recent evidence shows that neutrophils often migrate into the tumor and are associated with tumor progression. These tumor associated neutrophils (TANs) neutrophils have potential to induce angiogenesis, lymphangiogensesis and immunosuppression by inhibiting cytotoxic T lymphocytes. Immune status is one of the important prognostic factor of gastric cancer. We previously reported that lymphangiogenesis was augmented in the primary tumor of gastric carcinoma. Aim:The aim of this study was to investigate the correlation between CD15+ TANs and clinicopatological features of patients with gastric cancer. Materials and Methods: We investigated the association of the density of TANs in primary tumor with clinicopathological features by immunohistochemistry. We used specimens from a total of 143 primary tumor and 497 lymph nodes from 120 patients underwent gastrectomy between 2007 and 2008 in our department. We examined prognostic value of TANs identified as positive CD15 cells in both of the primary tumor and tumor draining lymph nodes. Results:The median number of TANs in primary tumor and tumor draining lymph nodes were 18.4 and 23 cells/HPF, respectively. High TANs in both of the primary tumor and lymph nodes had correlation with depth of invasion (primary tumor P&amp;lt;0.001, lymph nodes P=0.036) and lymph nodes metastasis (primary tumor P&amp;lt;0.001, lymph nodes P=0.002). Kaplan-Meier analysis showed that patients with high TANs in both primary tumor and lymph nodes had worse prognosis than patients with a low TANs (primary tumor P=0.031, lymph nodes P=0.014). Multivariate analysis revealed that high TANs in lymph nodes were independent prognostic factors. (P=0.038) Conclusion: Our results showed that patients with high CD15+TANs infiltration in gastric cancer tissues had poorer prognosis because of increasing lymph nodes metastasis. These findings suggested the TANs might have important role of tumor lymphangiogenesis in microenvironment of gastric carcinoma. Citation Format: Hiroaki Tanaka, Soichiro Hiramatsu, Tatsuro Tamura, Hisashi Nagahara, Kenjiro Kimura, Masatsune Shibutani, Go Ohira, Takahiro Toyokawa, Sadaaki Yamazoe, Ryosuke Amano, Kazuya Muguruma, Kiyoshi Maeda, Kosei Hirakawa, Masaichi Ohira. Infiltration of neutrophils in the tumor was associated with poor prognosis of patients with gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4001. doi:10.1158/1538-7445.AM2017-4001

Impact of obesity on short- and long-term outcomes of laparoscopy assisted distal gastrectomy for gastric cancer.

Laparoscopy assisted distal gastrectomy (LADG) for gastric cancer has been rapidly adopted for the treatment of both early and advanced gastric cancers which need lymph node dissection, but remains difficult procedure, especially in patients with obesity. We evaluated the impact of obesity on short- and long-term outcomes of LADG for gastric cancer. We retrospectively investigated 243 patients who underwent LADG for gastric cancer between January 2007 and December 2014. The patients were classified based on their body mass index (BMI) into the Obese (BMI≥25) and Non-Obese (BMI<25) Groups. Patient characteristics, clinicopathologic and operative findings, and short- and long-term outcomes were investigated and compared between the groups. The groups did not differ in age, sex, American Society of Anesthesiologists score, the presence of comorbidities, or pathologic stage. Operative time (265±46.6 vs. 244±55.6min; P=0.007) and estimated blood loss (113±101.4 vs. 66.5±95.2ml; P=0.007) were greater in the Obese Group. Fewer lymph nodes were retrieved in the Obese Group (38±23.7 vs. 47.5±24.3; P=0.004). No differences were evident in postoperative complication rate (20% vs. 17%; P=0.688) or the duration of postoperative hospital stay (9±8.5 vs. 9±5.1days; P=0.283) between the two groups. In the Obese Group, the 5-year overall survival rate was significantly lower than in the Non-Obese Group (67.6% vs. 90.3%; P=0.036). Furthermore, 5-year disease-specific survival was significantly lower in the Obese Group than in the Non-Obese Group (72.7% vs. 94.9%; P=0.015). LADG in patients with obesity could be performed as safe as in patients without obesity, with comparable postoperative results. But obesity may be a poor prognostic factor in gastric cancer.

Clinicopathologic significance of the CXCL1-CXCR2 axis in the tumor microenvironment of gastric carcinoma.

PurposeIt was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer.MethodsThe correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies. The effect of gastric cancer cells on the expression of CXCR2 in BM-MCs was examined using diffuse-type gastric cancer cell lines in vitro.ResultsThe expression of CXCL1 in cancer cells was correlated with T invasion (T2–T4), lymph node metastasis, lymphatic invasion, venous invasion, peritoneal cytology, peritoneal metastasis and CXCR2 expression in stromal cells. The expression of CXCR2 in stromal cells was correlated with macroscopic type-4 cancers, histological type, T invasion (T2–T4), lymph node metastasis, lymphatic invasion, infiltration, peritoneal cytology, peritoneal metastasis and CD271 expression in stromal cells. The overall survival of patients with CXCL1 and CXCR2-positive cancer was poorer than that of the patients with negative cancer. Both CXCL1 expression in cancer cells and CXCR2 expression in stromal cells were independent prognostic factors for gastric cancer patients.ConclusionThe expressions of CXCL1 in cancer cells and CXCR2 in stromal cells are useful prognostic factors for gastric cancer patients.

Individualized proximal margin correlates with outcomes in gastric cancers with radical gastrectomy.

The length of proximal margin for gastrectomy remains controversial. The proximal margin and its relationships with clinicopathological variables and overall survival of 922 gastric cancers were retrospectively analyzed. Proximal margin was divided into four groups (0-2.0, 2.1-4.0, 4.1-6.0, and >6.0 cm). It indicated that the overall survival was improved with the increase of proximal margin. The proximal margin of 2.1-4.0 cm was associated with a better overall survival for gastric cancers with solitary-type (T1 and T2 stages, N0 stage, tumor-node-metastasis stages I and II, tumor size <5 cm, histological G1 and G2, and Bormann type I and II). Futhermore, proximal margin of 4.1-6.0 cm was associated with a better overall survival for gastric cancers with infiltrative-type (T3 and T4 stages, N1 stage, tumor-node-metastasis stage III, tumor size ⩾5 cm, histological G3 and G4, and Bormann type III and IV). Univariate analysis revealed that T stage, N stage, tumor-node-metastasis stage, histological grade, Bormann type, carcinoembryonic antigen, carbohydrate antigen 199, extent of gastrectomy, tumor location, and proximal margin were significantly associated with overall survival. Multivariate analysis revealed that tumor-node-metastasis stage, histological grade, Bormann type, carcinoembryonic antigen, carbohydrate antigen 199, extent of gastrectomy, and proximal margin were independent prognostic factors for gastric cancers with radical gastrectomy. In conclusion, the proximal margin was an independent prognostic factor for gastric cancer and should be decided individually. Proximal margin of 2.1-4.0 cm and 4.1-6.0 cm were needed for patients with solitary-type and infiltrative-type, respectively.

Alpha-fetoprotein is a significant prognostic factor for gastric cancer: Results from a propensity score matching analysis after curative resection

BackgroundPrognosis of alpha-fetoprotein positive gastric cancer (AFPP-GC) remains elusive so far due to disparities in cohort size and baseline characteristics in previous studies. A propensity score matching (PSM) analysis as well as multivariable model was performed for unbiased evaluation of the outcome in AFPGC. MethodsAmong 3034 gastric cancer patients who underwent curative gastric cancer surgery (R0, M0) at the National Cancer Center, Korea between 2002 and 2007, we identified 97 patients being positive for AFP either by elevation of serum-AFP levels >10 μg/L or by immunohistochemical staining. Due to marked disparities in baseline characteristics and cohort size, propensity-score-matching was performed which matched 87 AFPP-GC patients to the same number of AFP-negative gastric cancer (AFPN-GC) patients. Baseline characteristics were compared using χ2-test. Survival curves were compared using the Kaplan-Meier-method and multivariable regression analysis was performed to evaluate the effect of AFP-positivity while adjusting the effects of confounding variables. ResultsAFPP-GC and AFPN-GC patients revealed marked disparities in patient cohorts. After PSM, groups were balanced for age, sex, tumor size, BMI, tumor location, grade of differentiation, presence of lymphatic vessel infiltration (LVI), Lauren histologic type and stage distribution. In multivariable regression analysis of the PSM-groups, only AFP-positivity and pathologic stage were predictive for overall survival (HR 2.98, CI 95% {1.7–5.1}, p < 0.0001). Five-year-survival rates were significantly worse for AFPP-GC patients (57.9% vs. 76.1%, p = 0.014). Recurrence was significantly more frequent in AFPP-GC patients (p = 0.003). ConclusionAFP can be considered as an independent negative predictor of overall and recurrence-free survival in patients with gastric cancer.

Clinical significance and prognostic value of Triosephosphate isomerase expression in gastric cancer.

Triosephosphate isomerase (TPI) is highly expressed in many human cancers and is involved in migration and invasion of cancer cells. However, TPI clinicopathological significance and prognostic value in gastric cancer (GC) are not yet well defined. The aim of the present work was to evaluate TPI expression in GC tissue and its prognostic value in GC patients.TPI expression was analyzed in 92 primary GC tissues and 80 adjacent normal mucosa tissues from GC patients undergoing gastrectomy by immunohistochemical analysis of tissue microarrays (TMAs). Univariate and multivariate analyses were performed to investigate TPI prognostic significance in GC patients.Immunohistochemical staining score showed that TPI expression in cancer tissues was significantly higher than in adjacent normal mucosa (P < .001). Univariate analysis revealed that TPI expression, depth of invasion, lympho node metastasis, tumor node metastasis (TNM) stage, and tumor diameter were associated with negative prognostic predictors for overall survival in GC patients (P < .05). High TPI expression represented a significant predictor of shorter survival in GC patients with positive lymphatic metastasis (P = .022) and tumor diameter >5 cm (P = .018). Cox multivariate analysis identified TPI expression, TNM stage, and tumor diameter as independent prognostic factors in GC patients.TPI expression might be considered as a novel prognostic factor to evaluate GC patients’ survival.

P-Akt as a potential poor prognostic factor for gastric cancer: a systematic review and meta-analysis.

To understand the relationship between p-Akt expression and the prognosis of patients with gastric cancer, we searched six databases, Pubmed, EMBASE, Cochrane Library, CNKI, Wanfang and CBM for relevant articles in order to conduct this metaanalysis. The pooled hazard ratios and corresponding 95%CI of overall survival were calculated to evaluate the prognostic value of p-Akt expression in patients with gastric cancer. With 2261 patients combined from 13 available studies, the pooled HR showed a poor prognosis in patients with gastric cancer in the univariate analysis (HR=1.88, 95%CI:1.45-2.43, P<0.00001), and the group “univariate analysis+estimate” (HR=1.41, 95%CI: 1.01-1.97, P=0.04), but not in multivariate analysis (HR=0.66, 95%CI: 0.29-1.52, P=0.33) and estimate (HR=1.13, 95%CI: 0.65-1.95, P=0.67). In conclusion, our results indicated that p-Akt was likely to be an indicator of poor prognosis in patients with gastric cancer.

胃癌における強力な予後因子である高度lymph node ratioに関わる包括的遺伝子探索

胃癌における強力な予後因子である高度lymph node ratioに関わる包括的遺伝子探索

Prognostic implication of hepatoduodenal ligament lymph nodes in gastric cancer.

There has been controversy regarding whether hepatoduodenal lymph node (HDLN) metastasis in gastric cancer is distant or regional metastasis. HDLN positivity was classified as distant metastasis in the 7th American Joint Committee on Cancer (AJCC) classification, but it was reclassified as regional lymph node metastasis in the 8th AJCC classification. The aim of our study is to verify prognostic significance of HDLN metastasis in gastric cancer.This retrospective study enrolled patients with gastric cancer who underwent D2 gastrectomy from January 2007 to June 2010. HDLN was classified as a regional lymph node.Total number of patients was 3175; 143 (4.5%) of them had HDLN metastasis. The HDLN positivity was significantly associated with older age, more advanced tumor stage, undifferentiated histologic type, and pathologic diagnosis of lymphatic, vascular, and perineural invasions. Five-year survival rate of HDLN-positive patients with stages I to III disease was significantly higher than that of stage IV group (59.3% vs 18.8%, P = 0.001). In patients with stage III disease, 5-year survival rate of HDLN-positive group was significantly lower than that of HDLN-negative group (51.7% vs 66.3%, P = 0.001). Multivariate analysis showed that HDLN metastasis was an independent prognostic factor.HDLN has a different prognostic significance from other regional lymph nodes in advanced stage of gastric cancer though its positivity is not considered as distant metastasis. HDLN positivity itself seems to be an independent prognostic factor in gastric cancer, and the survival outcomes of patients with stage III disease need to be reconsidered according to HDLN positivity.

DETECTION OF OCCULT LYMPH NODE TUMOR CELLS IN NODE-NEGATIVE GASTRIC CANCER PATIENTS

ABSTRACTBackground: The presence of lymph nodes metastasis is one of the most important prognostic indicators in gastric cancer. The micrometastases have been studied as prognostic factor in gastric cancer, which are related to decrease overall survival and increased risk of recurrence. However, their identification is limited by conventional methodology, since they can be overlooked after routine staining. Aim: To investigate the presence of occult tumor cells using cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically lymph node negative (pN0) by H&E. Methods: Forty patients (T1-T4N0) submitted to a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The results for metastases, micrometastases and isolated tumor cells were also associated to clinicopathological characteristics and their impact on stage grouping. Tumor deposits within lymph nodes were defined according to the tumor-node-metastases guidelines (7th TNM). Results: A total of 1439 lymph nodes were obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in 24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006) and perineural invasions (p=0.04), as well as peritumoral lymphocytic response (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally negative lymph nodes by H&E. The histologic stage of two patients was upstaged from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three among 12 CK-positive patients (25%) had disease recurrence (p=0.65). Conclusion: The CK-immunostaining is an effective method for detecting occult tumor cells in lymph nodes and may be recommended to precisely determine tumor stage. It may be useful as supplement to H&E routine to provide better pathological staging.

Body mass index (BMI) may be a prognostic factor for gastric cancer with peritoneal dissemination

BackgroundThe aim of this study is to investigate whether body mass index (BMI) is a prognostic factor in gastric cancer patients with peritoneal dissemination.MethodsThis is a retrospective study consisting of 518 patients with a histological diagnosis of gastric cancer with peritoneal dissemination seen at the Sixth Affiliated Hospital of Sun Yat-Sen University and Sun Yat-sen University Cancer Center between January 2010 and April 2014. Patients were followed until December 2015. Chi-square test and Kaplan-Meier survival analysis were used to compare the clinicopathological variables and prognosis.ResultsUnivariate analyses showed that significant prognostic factors included palliative gastrectomy (p < 0.001), tumor size (p < 0.001), tumor location (p = 0.011), peritoneal seeding grade (p < 0.001), ascites (p = 0.001), serum CEA level (p = 0.002), serum CA19-9 level (p = 0.033), palliative chemotherapy (p < 0.001), and BMI group (p < 0.001). For patients with palliative chemotherapy, univariate analysis revealed that palliative gastrectomy (p < 0.001), tumor size (p = 0.002), tumor location (p = 0.024), peritoneal seeding grade (p = 0.008), serum CEA level (p = 0.041), and BMI group (p < 0.001). Multivariate analysis revealed that BMI was an independent prognostic factor in gastric cancer patients with peritoneal dissemination, especially in patients who received palliative chemotherapy.ConclusionsBMI is a prognostic factor for patients who have gastric cancer with peritoneal dissemination, especially in those who received palliative chemotherapy.