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Introduction: Gastric cancer (GC)is the third leading cause of cancer-related deaths in China and immunotherapy emerging as a revolutionary treatment for GC recently. Tumor mutational burden (TMB) is a predictive biomarker of immunotherapy in multiple cancers. However, the prognostic significance and subtype of TMB in GC is not fully understood., Objectives: This study aims to evaluate the prognostic value of TMB in Chinese GC and further classify TMB-high GC (GC TMB-H ) patients combing with mutational signatures., Methods: Genomic profiling of 435 cancer-gene panel was performed using 206 GC samples from Chinese people. Actionable genetic alterations were compared across all the samples to generate actionable subtyping. The prognostic value of TMB in Chinese GC was evaluated. Mutational signatures were analyzed on TMB-H subtype to stratify the prognosis of TMB. Transcriptomic analysis was applied to compare the distributed immunocytes among different subtypes., Results: 88.3% (182/206) of GC samples had at least one mutation, while 45.1% (93/206) had at least one somatic copy number alteration (SCNA). 29.6% (61/206) of GC samples were TMB-H, including 13 MSI-H and 48 MSS tumors. According to distinct genetic alteration profiles of 69 actionable genes, we classified GC samples into eight molecular subtypes, including TMB-H, ERBB2 amplified, ATM mutated, BRCA2 mutated, CDKN2A/B deleted, PI3KCA mutated, KRAS mutated, and less-mutated subtype. TMB-H subtype presented a remarkable immune-activated phenotype as determined by transcriptomic analysis that was further validated in the TCGA GC cohort. GC TMB-H patients exhibited significantly better survival (P = 0.047). But Signature 1-high GC TMB-H patients had relatively worse prognosis (P = 0.0209, HR = 2.571) than Signature 1-low GC TMB-H patients from Chinese GC cohort, also validated in TCGA GC cohort, presenting highly activated carbohydrate, fatty acid or lipid metabolism., Conclusion: The Signature 1-high GC TMB-H could be a marker of poor prognosis and is associated with metabolism disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Accumulating evidence has been found that circular RNA (circRNA) plays a critical role in the initiation and development of various diseases by modulating gene expression in the cytoplasm. However, the role of circ_0044366 (termed circ29) in gastric cancer (GC) has yet to be elusive. We detected that exosomal circ29 was confirmed to be highly expressed in GC and can significantly impair the proliferation, migration, tube formation of HUVEC by exosomal communication. Interestingly, this effect could be blocked by the effect of miR-29a. In brief, we confirmed that circ29, as a sponge of miR-29a, plays a responsible role in the occurrence and development of GC by regulating the VEGF pathway. Therefore, it may be used as a potential target for the treatment of GC., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to characterize alterations in mucosa-associated microbiota in different anatomical locations of the stomach during gastric cancer progression and to identify associations between Helicobacter pylori infection and gastric microbial changes in patients with gastric cancer., Methods: Twenty-five H. pylori negative subjects with chronic gastritis and thirty-four subjects with gastric cancer were recruited, including H. pylori negative and positive patients with tumors in the antrum and the corpus. Gastric mucosa-associated microbiota were determined by 16S ribosomal RNA gene sequencing using a 454 sequencing platform., Results: We found that individuals with chronic gastritis from three different anatomical sites exhibited different microbiota compositions, although the microbial alpha diversity, richness and beta diversity were similar. Compared to patients with chronic gastritis, the gastric microbiota compositions were significantly different at the order level in the antrum and the corpus of patients with gastric cancer, which was dependent on the H. pylori infection status. Microbial alpha diversity and species richness, however, were similar between chronic gastritis and gastric cancer cases and independent of H. pylori status. The microbial community structure in patients with gastric cancer was distinct from that in patients with chronic gastritis. In addition, we found that the presence of H. pylori markedly altered the structure in gastric corpus cancer, but only mildly affected the antrum., Conclusion: Our data revealed distinct niche-specific microbiota alterations during the progression from gastritis to gastric cancer. These alterations may reflect adaptions of the microbiota to the diverse specific environmental habitats in the stomach, and may play an important, as yet undetermined, role in gastric carcinogenesis.

Gastric cancer (GC) ranks the third leading cause of global cancer mortality. Despite recent progress in surgery combined with chemotherapy, the outcomes of GC patients have barely improved. Therefore, better understanding of the molecular mechanisms involved in chemoresistance of GC may help develop novel strategies to treat this deadly disease. Previous evidence has shown aberrant expressions of USP14 in multiple malignancies, suggesting an important role of USP14 in tumorigenesis. However, its role in modulating chemoresistance in GC still remains elusive. In this study, we observed that USP14 levels were significantly increased in GC tissues compared to the paired normal tissues. Multivariate analysis demonstrated that USP14 level was an independent prognostic factor for DFS in GC patients. Silencing of USP14 promoted proteasomal degradation of p-ERK (T202/Y204) and p-Akt (T308/S473), thus inactivating Akt and ERK signaling pathways. Interestingly, silencing of USP14 alone was not sufficient to cause overt effects on cell growth, proliferation, and apoptosis, while resulting in significant apoptosis in the presence of cisplatin in GC cells. Thus, knockdown of USP14 sensitized GC cells to cisplatin by triggering cisplatin-induced apoptosis via impeding Akt and ERK signaling pathways. These results revealed a novel role of USP14 in modulating chemosensitivity of GC cells, suggesting USP14 may serve as not only a prognostic marker, but also a potential therapeutic target for GC patients., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Recent microRNA (miRNA) expression profiling studies suggest the clinical use of miRNAs as potential prognostic biomarkers in various malignancies. In this study, aiming to identify microRNAs with prognostic value for overall survival (OS) in stomach adenocarcinoma (STAD) patients, we analyzed the miRNA expression profiles and the associated clinical characteristics in 380 STAD samples from The Cancer Genome Atlas (TCGA) dataset. An eight-miRNA signature for predicting OS in STAD patients was identified and self-validated by survival analysis and semi-supervised principal components method. We developed a linear prognostic model composed of these miRNAs to divide patients into high- and low-risk groups according to the calculated prognostic scores. Kaplan-Meier analysis demonstrated that patients in the high-risk group had worse OS compared with patients in the low-risk group. Notably, this miRNA prognostic model showed prognostic significance to the STAD patients in early stages and the chemo-resistant patients, who would potentially benefit from additional medical interventions. Finally, this eight-miRNA signature is an independent prognostic biomarker and demonstrates a good predictive performance for 5-year survival. Thus, this signature may serve as a novel biomarker for predicting survival as well as chemotherapy response in STAD patients.

Gastric cancer is a leading cause of cancer-related mortality worldwide. Cancer stem cells are the source of tumor recurrence and metastasis. Self-renewal is a marker of cancer stem cells and also the basis of long-lasting survival and tumor progression. Although the mechanism of gastric cancer stem cell self-renewal is not clear, there are several signaling pathways and environmental factors known to be involved. This mini review describes recent developments in the self-renewal signaling pathway of gastric cancer stem cell research. Advancements made in this field of research will likely support the development of novel therapeutic strategies for gastric cancer.

Background: To initially assess the impact of perioperative blood transfusions (PBTs) on overall survival of patients underwent curative resection of Ⅰ-Ⅲ TNM stage gastric cancer (GC) using the propensity scoring method., Methods: The medical records of 1150 GC patients who underwent curative resection in the Tianjin Cancer Hospital between 2003 and 2008 were retrospectively analyzed. Both transfusion and nontransfusion patients were assessed the prognostic differences after surgery using the propensity score analysis., Results: A total of 299 GC patients (26.0%) were administrated the PBT. With the unadjusted analysis, patients with PBT presented older age, more operative blood loss, lower hemoglobin, lower albumin level, and higher risk of the advanced disease. The 5-y survival rate for patients with PBT was 31.0%, which was significantly lower than that (47.9%) of patients without PBT (P < 0.05). However, we demonstrated that there was not any statistical 5-y survival rate difference of between patients with PBT and patients without PBT with the propensity score analysis (31.0% versus 31.3%, P > 0.05). In addition, we also found that PBT was not significantly associated with the increasing risk of mortality (hazard ratio, 1.054; P = 0.628)., Conclusions: PBT could not give rise to the worse prognoses of GC patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Functional jejunal interposition (FJI) has been applied as a reconstruction procedure to maintain the jejunal continuity and duodenal food passage after total gastrectomy in patients with gastric cancer. The purpose of this study was to evaluate clinical efficacy of the FJI procedure by comparing the functional outcomes of FJI to Roux-en-Y after total gastrectomy in gastric cancer patients, and investigate physiologic mechanisms by which FJI exerts beneficial outcomes in beagles., Methods: Patients with stage I-IV gastric cancer without metastasis and recurrence one year after surgery were enrolled in this retrospective study. Seventy one patients received FJI and seventy nine patients received Roux-en-Y after total gastrectomy. We evaluated the nutritional status at three and twelve months and incidence of complications up to twelve months after surgery. Beagles receiving sham operation, FJI, or Roux-en-Y after total gastrectomy were sacrificed forty eight hours postoperatively. Beagles were gavaged with active carbon for evaluating the intestinal transit rate. Intestinal tissues from the duodenojejunal anastomosis were collected for examining interstitial cells of Cajal (ICC), inflammation, and apoptosis., Results: Compared to the bodyweight before surgery, the bodyweight loss at three and twelve months after surgery in patients receiving FJI was significant less than that in patients with Roux-en-Y. Patients with the FJI procedure showed significant increase of blood hemoglobin and total protein, compared to those at one month after surgery, and the prognostic nutrition index scores at three and twelve months after surgery. The incidence rates of post-operative complications, including reflux esophagitis, dumping syndrome, and Roux-en-Y syndrome were decreased in patients with FJI. Compared to beagles receiving Roux-en-Y, more ICC in the intestinal submuocsa, less intestinal epithelial cell apoptosis, and decreased inflammation in serosal side of the intestine were found in the FJI group. The intestinal transit rate in FJI group was lower than that in Roux-en Y group, indicating that FJI benefits food storage., Conclusion: The FJI procedure promotes nutritional recovery and decreases post-operative complications in gastric cancer patients after total gastrectomy, which may be through ameliorating intestinal inflammation and damage and reducing ICC loss to preserve food reservoir function and intestinal motility.

Background: This study aimed to elucidate the prognostic prediction superiority of the ratio between negative and positive lymph nodes (RNP) in gastric cancer (GC)., Methods: The clinicopathologic data of 1,563 GC patients were analyzed to demonstrate the prognostic significances of the RNP stage. The tumor RNP metastasis (TRNPM) classification system also was evaluated to determine the potential superiorities of the prognostic prediction for GC patients., Results: In the univariate survival analysis, both RNP stage and TRNPM classification were demonstrated to be relative factors in the overall survival (OS) of GC patients. Like the tumor-node-metastasis (TNM) and positive and dissected lymph node (TRPDM) classifications, the TRNPM classification was identified as an independently prognostic predictor of GC patients using multivariate survival analysis. However, TRNPM classification has smaller Akaike information criterion and Bayesian information criterion values than the TNM and TRPDM classifications, and TRNPM classification was demonstrated to be the most intensive indicator for the OS of GC patients using the case-control matched approach, which represented the comparative superiorities of prognostic prediction of TRNPM classification., Conclusion: The RNP stage should be considered as the optimal variable for evaluating the prognosis of GC in the clinic.

Zinc-finger protein 545 (ZNF545) was identified as a gastric tumour suppressor and potentially independent prognostic factor. At the present study, we found that lower expression of ZNF545 was specific in gastric cancer (GC) tissues, and the inconsistently methylated levels of ZNF545 promoter were identified in the gastric cancer tissues. In the methylation-specific PCR (MSP) analysis cohort, we found that GC patients with hypermethylated ZNF545 promoter exhibited significantly shorter median OS than those with unmethylated ZNF545 promoter and those with hypomethylated ZNF545 promoter. In the other cohort, we also demonstrated that GC patients with three or more methylated CpG sites in the ZNF545 promoter were significantly associated with poor survival by using the bisulphite gene sequencing (BGS). The methylated degrees of five CpG sites (-232, -214, -176, -144 and -116) could also provide distinct survival discrimination of patients with GC. These findings indicated that the methylated CpG sites of the ZNF545 promoter could be used for the clinical prediction of the prognosis of GC.

Background: It is still controversial whether tumor size (Ts) should be considered an important indicator for evaluation the prognosis of gastric cancer (GC). The purpose of this study was to elucidate the prognostic prediction superiority of Ts in the large-scale cohort of GC patients., Methods: Data from 1,521 patients who underwent the curative resection were analyzed for demonstration the prognostic value of Ts. In addition, a tumor size-node-metastasis (TsNM) classification system was proposed to evaluate the comparative superiorities of the prognostic prediction of GC patients., Results: With the univariate and multivariate analyses, Ts was identified as an independently prognostic predictor of GC patients, as was T stage. Ts was demonstrated to have smaller Akaike information criterion and Bayesian Information Criterion values within the Cox regression analyses than shown by T stage, which represented the optimum prognostic stratification. TsNM classification was also found to be competent for accurately prognostic evaluation of GC patients. The matched case-control logistic regression showed that TsNM classification could provide very powerful discriminations of patients' overall survival, compared with TNM classification. Additionally, Ts stage was found to enhance the survival discriminations in patients with certain clinicopathological characteristics, including male gender, T4a stage, N0 stage, diffuse type of Lauren classification, or age ≤60 years., Conclusions: Ts should be recommended as an important clinicopathologic variable to enhance the accuracy of the prognostic prediction of GC clinical patients.

Gastric cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with three primary tumors and two matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC). The HiC subtype of intratumoral heterogeneity was associated with older age, TP53 (tumor protein P53) mutation, enriched C > G transition, and significantly shorter survival, whereas the LoC subtype was associated with younger age, ARID1A (AT rich interactive domain 1A) mutation, and significantly longer survival. Phylogenetic tree analysis of whole-genome sequencing data from multiple samples of two patients supported the clonal evolution of GC metastasis and revealed the accumulation of genetic defects that necessitate combination therapeutics. The most recurrently mutated genes, which were validated in a separate cohort of 216 cases by targeted sequencing, were members of the homologous recombination DNA repair, Wnt, and PI3K-ERBB pathways. Notably, the drugable NRG1 (neuregulin-1) and ERBB4 (V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog 4) ligand-receptor pair were mutated in 10% of GC cases. Mutations of the BRCA2 (breast cancer 2, early onset) gene, found in 8% of our cohort and validated in The Cancer Genome Atlas GC cohort, were associated with significantly longer survivals. These data define distinct clinicogenetic forms of GC in the Chinese population that are characterized by specific mutation sets that can be investigated for efficacy of single and combination therapies.

Background: Protocadherin-10 (PCDH10) has been identified as a tumor suppressor gene in multiple carcinomas. In this study, we intended to elucidate the clinical applicability of the methylation of CpG sites of PCDH10 promoter for prognostic prediction in gastric cancer (GC)., Study Design: Qualitative and quantitative detections of PCDH10 promoter methylation were performed with methylation-specific polymerase chain reaction (MSP) and bisulphite genomic sequencing, respectively. The methylated statuses of 27 cytosine-phosphate-guanine (CpG) sites in PCDH10 promoter were detected in a series of 458 GC tissues to supply precise information of prognostic prediction. Associations between molecular, clinicopathologic, and survival data were analyzed., Results: Protocadherin-10 promoter methylation was found in 91.92% in all patients. Gastric cancer patients with 5 or more methylated CpG sites of PCDH10 promoter was significantly associated with poorer survival (p = 0.038). Meanwhile, methylation of combined CpG (-115, -108, -13, and +3) sites was also identified to provide elaborate survival discrimination for GC patients (p = 0.044). On multivariate survival analysis, methylation of combined CpG (-115, -108, -13, and +3) sites (hazard ratio [HR] = 1.255; p = 0.049) was identified to be an independent prognostic indicator of GC, as were N stage and T stage. Additionally, the methylation of combined CpG (-115, -108, -13, and +3) sites had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other 2 independent predictors of the survival. Ultimately, we demonstrated that the methylation of combined CpG (-115, -108, -13, and +3) sites was negatively associated with PCDH10 expression in GC tissues., Conclusions: The methylated CpG sites of PCDH10 promoter had significant applicability for clinical evaluation of the prognosis of GC., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Paired box gene 5 (PAX5), a member of the paired box gene family, is involved in control of organ development and tissue differentiation. In previous study, PAX5 promoter methylation was found in gastric cancer (GC) cells and tissues. At present study, we found that the inconsistently methylated levels of PAX5 promoter were identified in the different GC tissues. The methylated CpG site count and the methylated statuses of four CpG sites (-236, -183, -162, and -152) were significantly associated with the survival of 460 GC patients, respectively. Ultimately, the methylated CpG -236 was the optimal prognostic predictor of patients identified by using the Cox regression with AIC value calculation. These findings indicated that the methylated CpG -236 of PAX5 promoter has the potential applicability for clinical evaluation the prognosis of GC.

Background: It has recently been reported that the sixth edition of the tumor-node-metastasis (TNM) classification system for gastric cancer involving the staging of regional lymph nodes (N) has inappropriate cut-offs with regard to counts of metastatic lymph nodes. It remains controversial, however, as to whether the seventh edition of this classification system is completely accurate in staging N for the prediction of the prognosis of gastric cancer. Our aim was to determine which of these two editions of the TNM classification system was superior with regard to the prediction of the prognosis of Chinese patients with gastric cancer., Methods: We analyzed relevant clinicopathological data statistically from 1,563 patients with gastric cancer who had undergone curative resection to evaluate the sixth and seventh editions of the TNM classification system for N staging with regard to the prediction of overall survival (OS)., Results: Our survival analyses demonstrated that N staging via use of both the sixth and seventh editions of the TNM classification system was correlated with OS. Furthermore, case-control analysis indicated that the seventh edition was significantly superior to the sixth edition in predicting the OS of patients, regardless of the extent of lymphadenectomy (D1 or D2) and the number of dissected lymph nodes (<16 or ≥16). By taking into consideration both the extent of lymphadenectomy and the number of dissected lymph nodes simultaneously, we determined that the seventh edition of the TNM classification system was superior to the sixth edition regarding the evaluation of the OS in the various subgroups of gastric cancer patients., Conclusion: The seventh edition proved more reliable and accurate than the sixth edition of the TNM classification system in categorizing the number of metastatic lymph nodes for the purpose of predicting the OS of patients with gastric cancer after curative resection., (Copyright © 2014 Mosby, Inc. All rights reserved.)

The methylation of B-cell CLL/lymphoma 6 member B (BCL6B) DNA promoter was detected in several malignancies. Here, we quantitatively detect the methylated status of CpG sites of BCL6B DNA promoter of 459 patients with gastric cancer (GC) by using bisulfite gene sequencing. We show that patients with three or more methylated CpG sites in the BCL6B promoter were significantly associated with poor survival. Furthermore, by using the Akaike information criterion value calculation, we show that the methylated count of BCL6B promoter was identified to be the optimal prognostic predictor of GC patients.

RNF 180, a novel tumor suppressor, has been implicated in the carcinogenesis and progress of gastric cancer. At present study, we found that lower expression of RNA180 was specific in gastric cancer tissues, and the inconsistently methylated levels of RNF180 promoter were identified in the gastric cancer tissues. Importantly, we demonstrated that the methylated CpG site count and four hypermethylated CpG sites (-116, -80, +97, and +102) were significantly associated with the survival of 400 gastric cancer patients, respectively. With multivariate survival analyses, we demonstrated that both the methylation of combined CpG (-116, -80, +97, and +102) sites and N stage were the independent indictor of prognosis of gastric cancer patients. Eventually, the methylation of combined CpG (-116, -80, +97, and +102) sites was identified to have smaller AIC value than N stage by mean of AIC calculation with the Cox proportional hazards model. These findings indicated that the quantitative detection of RNF180 promoter methylation had the intensive feasibility for evaluation the prognosis of gastric cancer patients in clinic.

The objective of this study was to explore the prognostic prediction rationality of the seventh edition N stage for gastric cancer (GC) patients who underwent the limited lymphadenectomy. Clinicopathological data of 769 GC patients who underwent the curative resection between 1997 and 2006 were analyzed for demonstration that the seventh edition N stage had the significant superiorities of prognostic prediction to the patients who underwent the limited lymphadenectomy. Although the extent of lymphadenectomy was associated with the overall survival (OS) of gastric cancer (GC) patients, the N stages of the seventh edition of the TNM Classification were identified as the most intensively independent predictors of GC prognosis. Using stratum analysis, the 5-year survival rate of patients who underwent limited lymphadenectomy was observed to be significantly different from that of patients who underwent extended lymphadenectomy, regardless of the extent of lymph node metastasis. Multinomial logistic regression analysis revealed that combining the extents of lymph node metastasis and lymphadenectomy could improve the prediction accuracy of patient survival status. Case control analysis showed that regardless of the extent of lymphadenectomy, the seventh edition N stages featured significant superiority for OS evaluation of GC patients. The seventh edition N stage had the prediction rationality for the OS of GC patients who underwent the limited lymphadenectomy.

Purpose: Our aim was to investigate whether microRNAs can predict the clinical outcome of patients with gastric cancer. We used integrated analysis of microRNA and mRNA expression profiles to identify gastric cancer microRNA subtypes and their underlying regulatory scenarios., Experimental Design: MicroRNA-based gastric cancer subtypes were identified by consensus clustering analysis of microRNA profiles of 90 gastric cancer tissues. Activated pathways in the subtypes were identified by gene expression profiles. Further integrated analysis was conducted to model a microRNA regulatory network for each subtype. RNA and protein expression were analyzed by RT-PCR and tissue microarray, respectively, in a cohort of 385 gastric cancer cases (including the 90 cases for profiling) to validate the key microRNAs and targets in the network. Both in vitro and in vivo experiments were carried out to further validate the findings., Results: MicroRNA profiles of 90 gastric cancer cases identified two microRNA subtypes significantly associated with survival. The poor-prognosis gastric cancer microRNA subtype was characterized by overexpression of epithelial-to-mesenchymal transition (EMT) markers. This gastric cancer "mesenchymal subtype" was further validated in a patient cohort comprising 385 cases. Integrated analysis identified a key microRNA regulatory network likely driving the gastric cancer mesenchymal subtype. Three of the microRNAs (miR-200c, miR-200b, and miR-125b) targeting the most genes in the network were significantly associated with survival. Functional experiments demonstrated that miR-200b suppressed ZEB1, augmented E-cadherin, inhibited cell migration, and suppressed tumor growth in a mouse model., Conclusions: We have uncovered a key microRNA regulatory network that defines the mesenchymal gastric cancer subtype significantly associated with poor overall survival in gastric cancer., (©2013 AACR)

Suppressor of cytokine signaling-3 (SOCS-3), a multifunctional cytokine, is able to inhibit cell growth and migration by blocking the Janus kinase signal transducers and activators of transcription signaling (JAK/STAT) activation in oncogenesis. Although the STAT-3 expression was associated with lymph node metastasis from gastric cancer (GC), the implication of SOCS-3 expression in GC is not clearly elucidated. In this study, SOCS-3, STAT-3, and pSTAT-3 were evaluated in GC tissues and adjacent non-tumor tissues of 107 patients who underwent curative surgery by immunohistochemistry. Further, SOCS-3 and STAT-3 mRNA levels were also detected simultaneously. In addition, survival analysis was performed between clinicopathologic variables and prognosis of GC patients. Finally, correlative analysis was adopted for demonstration the best predicator of the survival independent factor. From the results, we demonstrated that only the lymph node metastasis was the independent predictor of the overall survival (OS) of GC patients, although SOCS-3, STAT-3, and other variables were significantly relative to OS. With multivariate logistical regression analysis, SOCS-3, STAT-3, and the status of extragastric nodal metastasis were identified to be the independent factors of the lymph node metastasis from GC. Ultimately, the SOCS-3 was the best predicator of lymph node metastasis from GC identified with the nominal regression analysis. Therefore, SOCS-3 should be considered as a potential indicator for prediction the lymph node metastasis from GC.

Objective: To demonstrate that the seventh edition of the tumor-node-metastasis (TNM) classification for gastric cancer (GC) should be updated with the number of negative lymph nodes for the improvement of its prognostic prediction accuracy., Methods: Clinicopathological data of 769 GC patients who underwent curative gastrectomy with lymphadenectomy between 1997 and 2006 were retrospectively analyzed to demonstrate the superiority of prognostic efficiency of the seventh edition of the TNM classification, which can be improved by combining the number of negative lymph nodes., Results: With the Cox regression multivariate analysis, the seventh edition of the TNM classification, the number of negative nodes, the type of gastrectomy, and the depth of tumor invasion (T stage) were identified as independent factors for predicting the overall survival of GC patients. Furthermore, we confirmed that the T stage-N stage-number of negative lymph nodes-metastasis (TNnM) classification is the most appropriate prognostic predictor of GC patients by using case-control matched fashion and multinominal logistic regression. Finally, we were able to clarify that TNnM classification may provide more precise survival differences among the different TNM sub-stages of GC by using the measure of agreement (Kappa coefficient), the McNemar value, the Akaike information criterion, and the Bayesian Information Criterion compared with the seventh edition of the TNM classification., Conclusion: The number of negative nodes, as an important prognostic predictor of GC, can improve the prognostic prediction efficiency of the seventh edition of the TNM classification for GC, which should be recommended for conventional clinical applications.

This study aims to explore the detailed signal transduction mechanism of epidermal growth factor receptor (EGFR)/signal transducers and activators of transcription 3 (STAT3) that contributes to the progression of gastric cancer (GC). The STAT3 expression, phosphorylated STAT3 (pSTAT3) expression, and EGFR expression were evaluated by using molecular detection methods of GC tissues, adjacent non-tumor tissues, GC cell lines, and normal gastric cell line. Cetuximab was administered in each cell line to demonstrate the correlations among the above biomarkers. Survival and relationship analyses were adopted to demonstrate the important mechanism of EGFR/STAT3 signaling pathway contributing to the progression of GC. STAT3 expression, pSTAT3 expression, and EGFR expression in GC tissues were significantly higher than those in adjacent non-tumor tissues, respectively. Similarly, we found that STAT3 expression, pSTAT3 expression, and EGFR expression were much higher in GC cell lines than those in GES-1 cell line. With cetuximab administration, both STAT3 expression and pSTAT3 expression in all GC cell lines decreased simultaneously. With Cox proportional hazards model analysis, pSTAT3 expression was identified as the independent predictors of the overall survival of GC patients, as was EGFR expression. Furthermore, we found that there were significant associations between STAT3 expression, pSTAT3 expression, EGFR expression, and lymph node metastasis in GC tissues. The activation of EGFR/STAT3 signaling pathway may contribute to lymph node metastasis, which can promote the progression of GC.

Background: The relationship between body mass index (BMI) and long-term outcome in gastric cancer patients following radical gastrectomy continues to be debated. We investigated the association between BMI, clinicopathological features, and prognosis in Chinese gastric carcinoma patients., Methods: A retrospective consecutive cohort study was performed on 1,296 patients who underwent gastrectomy with curative intent at the Tianjin Cancer Institute Hospital between 1999 and 2004. The clinicopathological characteristics, overall 5-year survival rate (OS), and preoperative and six-month postoperative BMIs of both overweight (BMI ≥ 25 kg/m(2); H-BMI; n = 364) and non-overweight (BMI <25 kg/m(2); N-BMI; n = 932) patients were compared., Results: Among these patients, 364 (28.1 %) were overweight. The OS was significantly higher in the H-BMI than N-BMI group (33.2 vs. 24.1 %, respectively; p < 0.001). Preoperative and six-month postoperative BMIs were 27.1 ± 2.0 and 24.8 ± 2.0 kg/m(2), respectively, in the H-BMI group (p < 0.001), whereas they were 21.7 ± 2.2 and 20.7 ± 2.2 kg/m(2), respectively, in the N-BMI group (p = 0.007). There was significantly better differentiation (p = 0.034), less distant metastases (p = 0.006), and a lower metastatic lymph node ratio (p = 0.014) observed in the H-BMI groups. Multivariate analyses indicated age, BMI, pathological tumor depth, distant metastases, metastatic lymph node ratio, and tumor size as independent prognostic factors., Conclusions: Our findings suggest that overweight patients were less likely to have tumors with aggressive features and can achieve ideal body weight following curative gastrectomy, possibly resulting in better long-term prognosis.

Background: The aim of this study was to investigate the relationship between the expression of hypoxia-inducible factor-1α (HIF-1α), Ras-related C3 botulinum toxin substrate 1 (Rac1), and vascular endothelial growth factor (VEGF), as well as their correlation with angiogenesis and prognosis in gastric carcinoma., Material and Methods: The expression of Rac1, HIF-1α, VEGF, and CD34 (described in terms of microvessel density, MVD) was determined by immunohistochemical staining of tissues from 60 radically resected gastric cancer specimens., Results: The proportion of specimens expressing Rac1, HIF-1α, and VEGF was 37/60 (61.7%), 35/60 (58.3%), and 40/60 (66.7%), respectively. The levels of Rac1, HIF-1α, and VEGF expression were significantly correlated with Lauren's classification, lymph node metastasis, and pathologic staging (p < 0.05). There were positive correlations between MVD and the expression of Rac1, HIF-1α, and VEGF. The mean survival time and 5-year survival rate in cases with positive Rac1, HIF-1α, and VEGF expression and MVD ≥ 26.3 were significantly shorter than those with negative Rac1, HIF-1α, and VEGF expression and MVD < 26.3., Conclusion: Rac1, HIF-1α, and VEGF play an important role in tumor invasion and metastasis, especially in tumor angiogenesis. Thus, testing the expression of Rac1, HIF-1α, and VEGF may be a useful index for treatment and prognosis., (Copyright © 2013 S. Karger AG, Basel.)

Objective: The aim of the study was to investigate the most appropriate system for categorization of metastatic lymph nodes among N staging (according to the 7th edition UICC/AJCC TNM Classification for Gastric Cancer), ratio between metastatic and examined lymph nodes (RML) staging, negative lymph nodes (NLN) staging and log odds of positive lymph nodes (LODDS) staging for evaluation the overall survival (OS) of gastric cancer., Methods: We reviewed clinicopathological data of 372 gastric cancer patients who underwent radical gastrectomy plus extended lymphadenectomy with the purpose of evaluating the differences in the OS according to different categories of metastatic lymph nodes., Results: Univariate and multivariate analysis of data significantly identified the degree of differentiation (HR = 1.404, p = 0.015), T staging (according to the 7th edition UICC/AJCC TNM Classification for Gastric Cancer) (HR = 1.568, p = 0.024) and the RML staging (HR = 1.479, p = 0.030) as independent predictors of the OS. However, RML staging was identified as the most appropriate for evaluating the OS of gastric cancer patients following radical gastrectomy plus extended lymphadenectomy rather than N staging, NLN staging and LODDS staging by using the case-control matched analysis. With the further stratified analysis, we demonstrated that RML staging had the best prognostic homogeneity than LODDS staging, NLN staging or N staging., Conclusions: RML staging was the best system for prediction the OS of the gastric cancer patients following radical gastrectomy plus extended lymphadenectomy, rather than LODDS staging, NLN staging or N staging., (Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Many issues of middle-third gastric cancer need to be address for obtaining preferably clinical treatment. The objective of this retrospective study was to analyze clinicopathologic characteristics and results of surgery for 113 middle-third gastric cancer patients admitted to our hospital. Retrospective cohort analyses of clinicopathologic data and postoperative prognosis of 113 middle-third gastric cancer patients who underwent curative resection between January 1997 and December 2003 were reviewed. Compared with lower-third gastric cancer patients, middle-third gastric cancer patients had significantly lower 5-year survival rate (P < 0.001) and higher recurrence rate (P < 0.001). With the Cox proportional hazards model analysis, the types of gastrectomy (hazard ratio (HR) = 0.495, P = 0.012) and ratio between metastatic and dissected lymph nodes (RML) (HR = 1.681, P < 0.001) were identified as the independent predictors of overall survival (OS) of middle-third gastric cancer patients. Besides, only RML (HR = 3.026, P < 0.001) was an independent predictor of recurrence for middle-third gastric cancer patients after surgery identified using the logistic regression analysis. The prognosis of middle-third gastric cancer was significantly worse than lower-third gastric cancer. RML was a key indicator for OS and recurrence of middle-third gastric cancer.

Objective: To date, there is no consensus to evaluate the most appropriate category of the nodal metastasis for precise predication the prognosis of gastric cancer patients with positive node metastasis after curative surgery., Methods: We retrospectively analyzed the clinicopathologic characteristics and overall survival (OS) of 299 gastric cancer patients with positive node metastasis after curative surgery for evaluation the optimal category of the nodal metastasis., Results: With the univariate and multivariate survival analyses, the depth of primary tumor invasion was identified as the independent predicators with the OS of 299 gastric cancer patients with nodal metastasis postoperatively, as were the number of positive lymph nodes (PLNs), the number of negative lymph nodes (NLNs), and the ratio between negative and positive lymph nodes (RNPL). The RNPL was identified to be more suitable for predication the OS of gastric cancer patients with positive node metastasis than the ratio between positive and dissected lymph nodes (RPDL) by using the stratum procedure of survival analysis. Besides, we found both PLNs and NLNs were independently correlated with OS of gastric cancer patients with nodal metastasis when RNPL, instead of RPDL, was controlled in the partial correlation model., Conclusions: RNPL, a new category of the nodal metastasis, was suitable for predication the OS of gastric cancer patients with nodal metastasis after curative resection, as were the PLNs, and NLNs.