Purpose: Pretreatment 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.Methods: This 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.Results: TRG 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 <28. PLR similarly predicted OS in patients <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).Conclusion: Pretreatment 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: 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.

As the neoadjuvant therapy has been successfully introduced in the treatment of gastrointestinal malignancies, the evaluation of therapeutic effectiveness is becoming increasingly important. Tumor-node-metastasis system has been widely applied. However, this system is mainly based on the location of residual tumor, but does not consider the amount of residual tumor. Tumor regression grading system, a quantitative method to assess the reaction of tumor to neoadjuvant treatment, could be used as a supplement to tumor-node-metastasis system and provide additional information on prognosis. To date, numerous gastrointestinal grading systems have been used in esophageal/esophagogastric junction carcinoma, gastric adenocarcinoma, colorectal cancer, and most of them were considered to associate with clinical outcomes. In this review, firstly, we expounded the importance of tumor regression grading systems, and summarized the histopathological changes after neoadjuvant therapy. Secondly, we introduced some commonly used gastrointestinal systems, as well as the relationships and nuance. Finally, we discussed pivotal issues about these systems. In this part, we explained the calculation methods based on grid points and square measures, discussed several factors leading to observer bias, containing the slice number and the grading tier number, and analyzed the factors that might affect clinical significance, covering anatomical location, the selection of survival index, and the tumor type. Tumor regression grade systems could be divided into two main classifications, the relative amount of fibrosis and residual tumor, and the proportion of residual tumor in the tumor bed. However, the definitions of these systems were still need to be improved. The tumor regression grading system is useful in evaluating tumor response to neoadjuvant therapy, but more work is needed to refine and unify the system.

PurposeTumor 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 MethodsA total of 290 patients with locally advanced gastric adenocarcinoma who underwent NCT and curative surgery were studied. Survival analysis for overall survival (OS) and disease-free 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. ResultsIn 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.ConclusionTRG was an independent predictor for survival, and there was no significant difference between these two systems.

Background: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. Methods: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. Results: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 10¹⁶). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. Conclusion: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.

Genome-Scale Analysis Identified NID2, SPARC, and MFAP2 as Prognosis Markers of Overall Survival in Gastric Cancer - Article abstract #929558