Shangxiang Chen

Preoperative C-Reactive Protein/Albumin Ratio Predicts Prognosis of Patients after Curative Resection for Gastric Cancer.

BACKGROUND: An elevated preoperative C-reactive protein/albumin (CRP/Alb) ratio has been reported to be associated with a poor prognosis for hepatocellular carcinoma. The aim of the present study was to investigate the prognostic value of the preoperative CRP/Alb ratio and compare it with other systemic inflammatory response markers in patients with gastric cancer (GC). METHODS: A retrospective study was performed in 455 patients with GC undergoing curative resection. We investigated the correlations between the preoperative CRP/Alb ratio and overall survival (OS). Kaplan-Meier and Cox regression models were used to assess independent prognostic factors. The area under the curve was used to compare the prognostic value of different markers. RESULTS: On multivariate analysis, the CRP/Alb ratio were independently associated with OS in patients with GC (hazard ratio: 1.626; 95% confidence interval: 1.191-2.219; P = .002), along with age (P = .003), preoperative body weight loss (P = .001), tumor location (P = .008), metastatic lymph node ratio (P < .001), and seventh tumor-nodes-metastasis stage (American Joint Committee on Cancer) (P = .007). However, several other systemic inflammation–based prognostic scores (neutrophil lymphocyte ratio, platelet lymphocyte ratio and systemic immune-inflammation index, Glasgow Prognostic Score, modified Glasgow prognostic score, and high-sensitivity modified Glasgow prognostic score) were not. In addition, the CRP/Alb ratio had a higher area under the curve value (0.625) compared with several other systemic inflammation–based prognostic scores (P < .001). CONCLUSION: The preoperative CRP/Alb ratio, a system inflammation-based prognostic score, is a superior predictor of OS in patients undergoing curative resection for GC and may help to identify the high-risk patients for treatment decisions.

Development and external validation of a prognostic nomogram for gastric cancer using the national cancer registry

A nomogram based on both western and eastern populations to estimate the Disease Specific Survival (DSS) of resectable gastric cancer (RGC) has not been established. In current study, we retrospectively analyzed 4,379 RGC patients who underwent curative resection from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed between 1998 and 2009 were assigned as training set (n= 2,770), and the rest were selected as SEER validation set (n= 1,609). An external validation was performed by a set of independent 1,358 RGC patients after D2 resection from Sun Yat–sen University Cancer Center (SYSUCC) in China. The nomogram was constructed based on the training set. The multivariate analysis identified that patients age at diagnosis, race, tumor location, grade, depth of invasion, metastatic lymph node stage (mLNS) and total number of examined lymph node (TLN) were associated with patients DSS. The discrimination of this nomogram was superior to that of the 7th edition of AJCC staging system in SEER validation set and SYSUCC validation set (0.73 versus 0.70, p=0.005; 0.76 versus 0.72, p=0.005; respectively). Calibration plots of the nomogram showed that the probability of DSS corresponded to actual observation closely. In conclusion, our nomogram resulted in more–reliable prognostic prediction for RGC patients in general population.

Combined preoperative concentrations of CEA, CA 19-9, and 72-4 for predicting outcomes in patients with gastric cancer after curative resection

In many cancers, prognostic factors are useful for identifying high-risk patients and in individualizing treatment. We sought to determine whether a combination of tumor markers (CTM) would improve prognostic accuracy in patients with gastric cancer (GC). The CTM score, which is derived from serum concentrations of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and carbohydrate antigen 72-4 (CA 72-4), was tested retrospectively in 1134 patients with GC undergoing curative resection between October 2000 and December 2012. The CTM score was 2 for patients with two or three elevated markers, 1 for those with one elevated marker, and 0 for those no elevated markers. Overall survival (OS) in patients with CTM scores 0, 1, and 2 was 61.8%, 31.4%, and 15.1%, respectively (P<.001). The CTM score independently predicted OS on multivariate analysis (HR, 1.95; 95% CI, 1.73 to 2.21; P<.001). Moreover, the area under the receiver operating characteristics curve of the CTM score (0.67; 95% CI, 0.64 to 0.70) was higher than the values of any individual marker (0.63, 0.57, 0.57; P<.001 for all comparisons). The CTM score independently predicted postoperative survival in GC, and it may have better clinical utility than individual tumor markers for identifying high-risk patients with GC.

Nomogram based on systemic inflammatory response markers predicting the survival of patients with resectable gastric cancer after D2 gastrectomy

This study aimed to construct a nomogram to predict survival of patients with resectable gastric cancer (RGC) based on both clinicopathology characteristics and systemic inflammatory response markers (SIRMs). Of 3,452 RGC patients after D2 gastrectomy at the Sun Yat-sen University Cancer Center, 1058 patients who met the inclusion criterion were analyzed. The patients operated on from January 1, 2005 to December 31, 2009 were assigned to the training set (817 patients) to establish a nomogram, and the rest (241 patients) were selected as validation set. Based on the training set, seven independent risk factors were selected in the nomogram. The calibration curves for probability of 1-year, 3-year and 5-year overall survival (OS) showed satisfactory accordance between nomogram prediction and actual observation. When the metastatic lymph node stage (mLNS) is replaced by metastasis lymph node ratio (mLNR) in validation set, the C-index in predicting OS rise from 0.77 to 0.79, higher than that of 7th American Joint Committee on Cancer 7th (AJCC) staging system (0.70; p<0.001). In conclusions, the proposed nomogram which including mLNR and routine detected SIRMs resulted in optimal survival prediction for RGC patients after D2 gastrectomy.

Prognostic value of pretreatment albumin–globulin ratio in predicting long-term mortality in gastric cancer patients who underwent D2 resection

Background Several studies have highlighted the prognostic value of the albumin–globulin ratio (AGR) in various kinds of cancers. Our study was designed to assess whether AGR is associated with the prognosis of gastric cancer patients. Patients and methods A total of 507 gastric cancer patients between 2005 and 2012 were included. The AGR was defined as the ratio of serum albumin to nonalbumin and calculated by the equation: albumin/(total protein − albumin). Furthermore, AGR was divided into two groups (low and high) using the X-tile software. Survival analysis stratified by AGR groups was performed. Results The mean survival time for each group was 36.62 months (95% CI: 33.92–39.32) for the low AGR group and 48.95 months (95% CI: 41.93–55.96, P=0.003) for the high AGR group. Patients in the high group (AGR ≥1.93) had a significantly lower 5-year mortality in comparison with the low group (AGR <1.93) (52.4% vs 78.5%, P=0.003). The high AGR group showed obviously better overall survival than the low AGR group according to Kaplan–Meier curves (P=0.003). Multivariate analysis showed that AGR was an independent predictive factor of prognosis in gastric patients. Conclusion Pretreatment AGR is a significant and independent predictive factor of prognosis.

The Effects of Anti-inflammatory Drug Treatment in Gastric Cancer Prevention: an Update of a Meta-analysis.

Gastric cancer has high incidence and fatality rates, making chemoprevention agents necessary. There is an ongoing debate about aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) use can significant reduce the risk of GC. We conducted a meta-analysis of existing studies evaluating the association of anti-inflammatory drug and GC. We performed a systematic literature search of PubMed, Web of Science, Embase, OVID, Cochrane Library and Clincialtrials.gov up to August 31, 2015. Either a fixed-effects or a random-effects model using was based on the result of homogeneity analysis. Subgroup, sensitivity, meta-regression, and publication bias analyses were evaluated. Forty-seven studies were finally included in this meta-analysis. The overall GC risk reduction benefit associated with anti-inflammatory drug use represented an RR of 0.78 (95% CI 0.71 to 0.85) and an adjusted RR of 0.74 (95% CI 0.71 to 0.77). Besides, the prevention benefit of aspirin/NSAIDs ingestion appeared to be confined to those patients with regiment of short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day). Further, our data also suggest that COX-2 inhibitors use is a more effective approach in GC prevention (RR, 0.45; 95% CI, 0.29-0.70). In this meta-analysis, our finding support short or middle-term (≤5 years), high-frequency (>30 times per month) and low dose (<200 mg per day) aspirin/NSAIDs intake is a well method for GC prevention and also confirm the inverse association between aspirin/NSAIDs use and GC risk. Additionally, selective COX-2 inhibitors use probably a more effective approach to reduce GC risk.

Combination of CRP and NLR: A better predictor of postoperative survival in patients with gastric cancer

Objectives C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR) were independent predictive factors for gastric cancer (GC). Our study was designed to prove the prognostic value of the combination of CRP and NLR (COC-NLR) in GC patients. Materials and methods A total of 1,058 GC patients who underwent D2 resection from Sun Yat-Sen University Cancer Center between 2003 and 2013 were included. They were divided into three groups (low: NLR ≤2.5, CRP ≤6.1; medium: NLR >2.5, CRP ≤4.5; high: NLR >2.5, CRP >4.5 or NLR ≤2.5, CRP >6.1) by the random forest method. Survival analysis stratified by COC-NLR groups was performed. Results The mean survival time for each group was: for the low group 75.44 months (95% CI: 72.48–78.40), the medium group 56.50 months (95% CI: 50.68–62.31), and the high group 38.65 months (95% CI: 34.51–42.97). The low group showed obviously better overall survival (OS) than other two groups (p<0.001). Survival analysis showed that COC-NLR had statistical significance in both univariate and multivariate analyses (p<0.01). Conclusion This study showed that COC-NLR could work as an independent prognostic factor in GC and provide more accurate prediction than single NLR or CRP.

Lymph nodes ratio based nomogram predicts survival of resectable gastric cancer regardless of the number of examined lymph nodes

To develop a nomogram to predict the prognosis of gastric cancer patients on the basis of metastatic lymph nodes ratio (mLNR), especially in the patients with total number of examined lymph nodes (TLN) less than 15. The nomogram was constructed based on a retrospective database that included 2,205 patients underwent curative resection in Cancer Center, Sun Yat-sen University (SYSUCC). Resectable gastric cancer (RGC) patients underwent curative resection before December 31, 2008 were assigned as the training set (n=1,470) and those between January 1, 2009 and December 31, 2012 were selected as the internal validation set (n=735). Additional external validations were also performed separately by an independent data set (n=602) from Jiangxi Provincial Cancer Hospital (JXCH) in Jiangxi, China and a data set (n=3,317) from the Surveillance, Epidemiology, and End Results (SEER) database. The Independent risk factors were identified by Multivariate Cox Regression. In the SYSUCC set, TNM (Tumor-node-metastasis) and TRM-based (Tumor-Positive Nodes Ratio-Metastasis) nomograms were constructed respectively. The TNM-based nomogram showed better discrimination than the AJCC-TNM staging system (C-index: 0.73 versus 0.69, p<0.01). When the mLNR was included in the nomogram, the C-index increased to 0.76. Furthermore, the C-index in the TRM-based nomogram was similar between TLN ≥16 (C-index: 0.77) and TLN ≤15 (C-index: 0.75). The discrimination was further ascertained by internal and external validations. We developed and validated a novel TRM-based nomogram that provided more accurate prediction of survival for gastric cancer patients who underwent curative resection, regardless of the number of examined lymph nodes.

Phosphorylation by mTORC1 stablizes Skp2 and regulates its oncogenic function in gastric cancer

BackgroundBoth mTOR and Skp2 play critical roles in gastric cancer (GC) tumorigenesis. However, potential mechanisms for the association between these two proteins remains unidentified.MethodsThe regulatory role for mTORC1 in Skp2 stability was tested using ubiquitination assay. The functions of p-Skp2 (phosphorylation of Skp2) were studied in vitro and in vivo. Expression of p-Skp2 and p-mTOR (phosphorylation of mTOR) were shown in GC lines and in 169 human primary GC tissues.ResultsmTORC1 can directly interact with Skp2 and phosphorylated Skp2 at Ser64, which sequentially protect Skp2 from ubiquitination and degradation. Furthermore, the phospho-deficient p-Skp2 (S64) mutant significantly suppresses GC cell proliferation and tumorigenesis. The expression of p-Skp2 was associated with p-mTOR in GC cell lines and tissues. Interestingly, the combination of p-Skp2 and p-mTOR was a better predictor of survival than either factor alone.ConclusionThe mTORC1 function to regulate Skp2 by Ser64 phosphorylation may represent an oncogenic event in GC tumorigenesis. Moreover, our study also indicates that Skp2 Ser64 expression is a potential indicator in the treatment of GC patients using mTORC1 inhibitor.

Prognostic Impact of the Signet Ring Cell Type in Node-Negative Gastric Cancer

Little is known regarding the prognostic impact of the signet ring cell (SRC) histotype on negative lymph nodes (LNs) in gastric cancer (GC). In this study, we aimed to investigate the differences between SRC and non-SRC GC patients without LN metastasis. The medical records of patients with GC who underwent gastrectomy at Sun Yat-Sen University Cancer Centre from 1996 to 2012 were reviewed to analyse the clinicopathologic characteristics associated with survival. A total of 480 cases of GC patients without LN metastasis were identified, which included 90 SRC GC patients and 390 non-SRC GC patients. Between the two groups, there were a host of significant differences in the American Joint Committee on Cancer, 7th edition (AJCC) stage. We found that SRC histology was correlated with a poor prognosis in terms of recurrence in node-negative GC patients and that SRC histologic analysis combined with AJCC staging maybe an effectual method for prediction of the recurrence rate. Additionally, we found that SRC GC presents a more dismal overall prognosis in patients with perineural or vascular invasion.