Background Serum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery. Methods In total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher’s exact test. Multivariate analyses were performed by the Cox regression model. Results Pre- and post-CA199, −CA125 and -CA724 could predict overall survival (all P < 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, −CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P < 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05). Conclusions CA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.

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PurposePretreatment neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios are markers of systemic inflammation. In patients with locally advanced gastric cancer (GC), the utility of these ratios in predicting tumor regression grade (TRG) after neoadjuvant chemotherapy (NCT) remains unclear.MethodsThis retrospective study examined 283 locally advanced GC patients who underwent NCT and radical surgery. The receiver operating characteristic (ROC) curve analysis and the Youden index were applied to identify optimal NLR/PLR cutpoints. The Kaplan–Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Univariate/multivariate analyses were conducted by the logistic regression method.ResultsTRG grade proved significantly worse in patients with high values of both NLR and PLR whether in univariate (OR = 3.457; p = 0.044) or multivariate (OR = 6.876; p = 0.028) analysis. The degree of tumor differentiation was an independent predictive factor for TRG (OR = 2.874; p = 0.037) in multivariate analysis. In the subgroup analyses, NLR predicted OS (p = 0.04) and DFS (p = 0.03) in female patients, whereas PLR was predictive of both OS (p = 0.026) and DFS (p = 0.018) in patients with clinical TNM stage 3 disease and dissected lymph node counts &lt;28. PLR similarly predicted OS in patients &lt;65 years old (p = 0.049), those with positive lymph nodes (p = 0.021), or those with moderate or poorly differentiated tumors (p = 0.049).ConclusionPretreatment NLR and PLR together serve to independently predict TRG after NCT and surgery in patients with locally advanced GC. Screening for patients with high NLR and PLR values may allow them to benefit upfront from alternatives to NCT.

Background Gastric cancer is the most common gastrointestinal tumor, and the rates of recurrence and metastasis are high. Research results on molecular biomarkers used for prognosis of gastric cancer remain inconclusive. This study aimed to explore the gene expression module of gastric cancer and to determine potential prognostic biomarkers. Material/Methods Three microarray datasets (GSE13911, GSE79973, and GSE29272) from Gene Expression Omnibus (GEO), including 206 pairs of gastric tumors and adjacent normal samples, were used for analysis of differentially expressed genes (DEGs). The 3 microarray datasets yielded 144 genes associated with the progression and prognosis of gastric cancer. After this, a risk score model was developed for result validation using an independent dataset from The Cancer Genome Atlas. Results The validation of the independent dataset showed significantly increased NID2 , SPARC , and MFAP2 expression in gastric tumor tissues, which were associated with poor outcomes in gastric cancer patients. Moreover, the high risk score obtained was associated with poor overall survival (HR: 1.787; 1.069–2.986; P =0.027). Subgroup analyses revealed that these significant prognostic values were detected in patients aged <65.0 years, tumors in the antrum/distal colon, grade 3 tumors, or TNM-M0 stages of cancer. Conclusions The findings of this study show that NID2 , SPARC , and MFAP2 are upregulated in gastric tumor tissues and are significantly associated with poor overall survival. Therefore, the predictive values of the risk score model employed for the prognosis of gastric cancer could be improved by using these 3 upregulated DEGs.

Tumor regression grade (TRG) has been widely used in gastrointestinal carcinoma to assess pathological responses to neoadjuvant chemotherapy (NCT). There are various standards without a consensus, and it is still unclear which kind of system has better predictive value. This study aims to investigate and compare the predictive ability of the Mandard and Becker TRGs in patients with locally advanced gastric cancer. Materials and Methods A total of 290 patients with locally advanced gastric adenocarcinoma who underwent NCT and curative surgery were studied. Survival analysis for overall survival (OS) and diseasefree survival (DFS) were based on the Kaplan-Meier method and Cox proportional hazards method. Predictive values of TRGs and models were assessed by time-dependent receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), nomogram, and calibration curve. Results In multivariable analysis, the Mandard TRG was associated with OS (hazard ratio [HR], 1.806; p=0.026) and DFS (HR, 1.792; p=0.017). The Becker TRG was also related to OS (HR, 1.880; p=0.014) and DFS (HR, 1.919; p=0.006). The Mandard and Becker TRG AUCs for 5-year survival were 0.72 and 0.71, respectively. The whole models showed an increased predictive value, with AUCs of 0.85 and 0.86, respectively. There was no significant difference between the two TRGs and two models. Conclusion TRG was an independent predictor for survival, and there was no significant difference between these two systems.

Background. Tumor regression grade (TRG) is widely used in gastrointestinal carcinoma to evaluate pathological responses to neoadjuvant chemotherapy (NCT), but whether it is an independent prognostic factor is still controversial. The aim of this study is to investigate the value of TRG in locally advanced gastric adenocarcinoma patients who underwent NCT and curative resection. Methods. Pathological regression was reevaluated according to the Mandard TRG. Survival curves were obtained by the Kaplan–Meier method, and differences in overall survival (OS) and disease-free survival (DFS) were compared using the log-rank test. Univariate and multivariate analyses for survival were based on the Cox proportional hazards method. Results. In total, 290 patients were identified in our electronic database. In univariable analysis, TRG was associated with OS (HR=3.822, P≤0.001) and DFS (HR=3.374, P≤0.001). However, in multivariable analysis, TRG was not an independent factor for OS (P=0.231) or DFS (P=0.191). In the stratified analysis, TRG retrieved prognostic significance in patients with the metastasis of lymph node (HR=2.034, P=0.035 for OS; HR=2.220, P=0.016 for DFS), while not in patients with negative lymph node (P=0.296 for OS; P=0.172 for DFS). Conclusions. TRG was not an independent predictor for survival, but the system regained its predicting significance in patients with lymph node metastasis.

IntroductionAs neoadjuvant chemotherapy (NCT) has been successfully introduced in gastric cancer (GC), more biomarkers are needed to evaluate the efficacy. Cancer-associated fibroblasts (CAFs) is associated with chemoresistance and prognosis. Three biomarkers, CD10, fibroblast activation protein-α (FAP) and G-protein-coupled receptor 77 (GPR77), have been proved to express in CAFs. However, their predictive values for efficacy of NCT and prognosis in gastric cancer is unknown.MethodsTotally, specimens of 171 locally advanced gastric cancer patients who underwent NCT and D2 radical gastrectomy and matched preoperative biopsy specimens were retrospectively analyzed. Tumor regression grade (TRG) is reevaluated according to Mandard TRG. Expressions of CD10, FAP and GPR77 in CAFs before NCT (pre-) and after NCT (post-) were evaluated by immunohistochemistry. Survival curves on overall survival (OS) were obtained by Kaplan-Meier method, and differences were analyzed by log-rank test. Associations between categorical variables were explored by chi-square test or Fisher’s exact method. Univariable and multivariate analyses were performed by logistic regression model and Cox proportional hazard regression model.ResultsHigh expressions of post-CD10, post-FAP, post-GPR77 and pre-CD10 were related to worse TRG (all p&lt;0.05). In multivariable analysis, post- and pre-FAP were independent predictive factors to TRG (p&lt;0.010). Post-CD10 (p=0.032) and post-FAP (p=0.013) were related to OS in univariable analysis, but none of biomarkers were independent prognostic factors in multivariable analysis.ConclusionsExpressions of CD10, FAP and GPR77 in CAFs were related to chemoresistance and overall survival, and these biomarkers have predictive values for tumor regression and prognosis in locally advanced gastric cancer patients.

Background: Serum tumor markers are of great importance in diagnosis, prognostic predicting and recurrence monitoring in gastrointestinal malignancy, including AFU, AFP, CEA, CA199, CA125 and CA724. However, their significances in gastric cancer (GC) patients with neoadjuvant therapy (NCT) are still uncertain. The aim of this study is to evaluate the predictive value of these six tumor markers in locally advanced GC patients with NCT and curative surgery. Methods: 290 locally advanced GC patients with NCT and D2 radical gastrectomy were retrospectively analyzed. Their tumor markers before (pre-) and after (post-) NCT and pathological characters were exacted from the database in our hospital. The optimal cutoff values of six tumor markers were calculated by ROC and Youden index. Their predictive significances were analyzed and survival curves on overall survival (OS) were obtained by Kaplan-Meier method. Associations between categorical variables were explored by Chi-square test or Fisher's exact method. Multivariate analyses were performed by Cox regression model. Results: Not only the pre- and post- CA199, CA125 and CA724 could predict the OS respectively, but also the changes (diff-) between post- and pre- groups were related to the prognosis (P < 0.05). In multivariable analysis, only pre- (P = 0.016) and post-CA724 (P = 0.033) remained significant, and the significance of diff-CA724 was on borderline (P = 0.085). Besides, pre- and post-CA199, CA125 and CA724 were associated with the metastasis of lymph node (N- vs N+) and pathological stage (Ⅰ-Ⅱ vs Ⅲ) (P < 0.05). Post-CA724 was related to the invasion of vascular or lymphatic vessels (P = 0.019), and pre-CA724 was nearly remarkable (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05). Conclusions: CA724 is an independent factor to prognosis, and could be used to predict the ypN and ypTNM stage in locally advanced GC patients undergone NCT and curative resection.