Rupeng Zhang

The pattern and risk factors of recurrence of proximal gastric cancer after curative resection

To explore the time and pattern of recurrence of proximal gastric cancer and estimate the risk factors and prognostic factors for it. Considering these risk factors, postoperative adjuvant therapies and follow‐up program can be individualized.

STAT3 is associated with lymph node metastasis in gastric cancer

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.

The RML of lymph node metastasis was superior to the LODDS for evaluating the prognosis of gastric cancer

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.

Long non-coding RNA PTENP1 functions as a ceRNA to modulate PTEN level by decoying miR-106b and miR-93 in gastric cancer

Recent studies have shown that competing endogenous RNAs (ceRNAs) play an important role in the regulation of gene expression, and participate in a wide range of biological processes, including carcinogenesis. Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, has been reported to exert its tumor suppressive function via modulation of PTEN expression in many malignancies. However, whether a PTENP1∼miRNA∼PTEN ceRNA network exists and how it functions in gastric cancer (GC) remains elusive. In order to identify and characterize the PTENP1∼miRNA∼PTEN ceRNA network in GC, we first determined PTENP1 levels in clinical GC samples and found that PTENP1 and PTEN were concurrently downregulated in these samples. We further demonstrated that PTENP1 could act as a ceRNA to sponge miR-106b and miR-93 from targeting PTEN for downregulation using a novel ceRNA in vitro gradient assay. Thus, we revealed a tumor suppressive role of PTENP1 as ceRNA in GC and pinpointed the specific miRNAs decoyed by PTENP1, highlighting the emerging roles of ceRNAs in the biological regulation of GC cells and their possible clinical significance.

Lymph node metastasis is mediated by suppressor of cytokine signaling-3 in gastric cancer

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.

A retrospective clinicopathologic study of remnant gastric cancer after distal gastrectomy.

Introduction:Remnant gastric cancer (RGC) is a unique clinical entity with relatively less frequency in gastric cancer series and often reported to be detected at advanced stages and had poor prognosis. Methods:A total of 112 patients with RGCs from July 1991 to July 2008 were enrolled in this retrospective analysis. Results:A total number of 112 cases were composed of 20 (17.8%) differentiated carcinomas and 92 (82.2%) undifferentiated carcinomas. There are 64 (57.1%) patients with tumor at anastomotic site and 48 (42.9%) tumor at nonanastomotic site. The diameter of tumors was ≥4 cm in 83 (74.1%) patients. Borrmann III, IV accounted for 70.5% and 17.8% respectively. Three (2.6%) patients were classified as stage I, 16 as stage II (14.2%), 62 as stage III (55.3%), and 31 (27.6%) as stage IV. Percentage of T4 stage was 57.1%. Distant metastasis rate and lymph node metastasis rate were 27.6% and 58.9%, respectively. There were numerous clinicopathologic differences according to different original disease, initial reconstruction, and tumor location. The median overall survival time was 27.9 months. TNM stage and option of treatments were independent prognostic factors in multivariable analysis. Conclusions:The lifelong annual follow-up endoscopic examinations after the initial gastrectomy and radical resection may help to improve the prognosis of RGCs.

Outcome in relation to numbers of nodes harvested in lymph node-positive gastric cancer

AIMS We conducted a retrospective case-control study to compare the prognostic differences of lymph node-positive gastric cancer patients between dissected lymph nodes (DLNs) <15 group and DLNs > or =15 group. METHODS A retrospective study of 323 lymph node-positive gastric patients who underwent potentially curative resection for gastric cancer was analyzed to identify the prognostic differences between DLNs <15 group and DLNs > or =15 group. Of these patients, 49 patients with <15 DLNs were matched with 147 patients with > or =15 DLNs according to gender, age, location of primary tumor, and type of gastrectomy. RESULTS Patients with n1 lymph node metastasis (according to JCGC), serosal involvement, ratio of positive lymph nodes less than 25%, or without adjuvant chemotherapy in > or =15 DLN group had comparatively longer median survival than patients with homologous clinicopathologic variables in <15 DLN group, respectively. Patients with n1 stage lymph node metastasis, serosal involvement, non-intestinal Lauren classification, or without adjuvant chemotherapy in <15 DLN group had higher recurrence rate than patients with homologous clinicopathologic variables in > or =15 DLN group, respectively. In addition, we demonstrated that patients with more than n1 stage lymph node metastasis in <15 DLN group had higher rate of peritoneal dissemination than those with more than n1 lymph node metastasis in > or =15 DLN group. CONCLUSIONS DNL > or =15 was an important factor to improve the prognosis of lymph node-positive gastric cancer patients after potential curative resection.

Overexpression of SMYD3 was associated with increased STAT3 activation in gastric cancer

This study aimed to investigate mRNA and protein expressions of SET and MYND domain-containing protein 3 (SMYD3), STAT3, and phosphorylated STAT3 (pSTAT3) in gastric cancer (GC). This study was also conducted to explore the correlations between these proteins and biological behaviors of GC. SMYD3, STAT3, and pSTAT3 expressions were detected in GC tissues and adjacent non-tumor tissues by semiquantitative/quantitative reverse transcription polymerase chain reaction and Western blot analysis. SMYD3, STAT3, and pSTAT3 expressions in tissue sections were evaluated by immunohistochemistry. Staining results were compared with clinicopathological characteristics and the outcome of patients. The mRNA expression levels of SMYD3 or STAT3 and the protein expression levels of SMYD3, STAT3, or pSTAT3 in GC tissues were significantly higher than those in adjacent non-tumor tissues. Lymph node metastasis was identified as an independently relative factor for SMYD3 expression; the degree of differentiation and serosal invasion were identified as the independently relative factors for pSTAT3 expression in GC tissues. SMYD3 expression and STAT3 or pSTAT3 expressions in GC tissues were significantly and positively correlated. Multivariate analysis results demonstrated that primary tumor location, lymph node metastasis, SMYD3 expression, and pSTAT3 expression were independent prognostic indicators of GC. pSTAT3 expression was an optimal prognostic predictor of patients, as identified by Cox regression with Akaike’s information criterion value calculation. High SMYD3 and pSTAT3 expressions may indicate poor prognosis of patients with GC.

Superiority of the Ratio Between Negative and Positive Lymph Nodes for Predicting the Prognosis for Patients With Gastric Cancer

BackgroundThis study aimed to elucidate the prognostic prediction superiority of the ratio between negative and positive lymph nodes (RNP) in gastric cancer (GC).MethodsThe 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.ResultsIn 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.ConclusionThe RNP stage should be considered as the optimal variable for evaluating the prognosis of GC in the clinic.

Negative Node Count Improvement Prognostic Prediction of the Seventh Edition of the TNM Classification for Gastric Cancer

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.