Application of Circulating Tumor Cells and Circulating Free DNA from Peripheral Blood in the Prognosis of Advanced Gastric Cancer

Objective. To explore the application value of circulating tumor cells (CTCs) and circulating free DNA (cfDNA) from peripheral blood in the prognosis of advanced gastric cancer (AGC). Here, we measured CTCs and cfDNA quantity for predicting the outcome of patients. Patients and Methods. Forty-five patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and surgical treatment were enrolled in this study. All patients received neoadjuvant chemotherapy with paclitaxel + S-1 + oxaliplatin (PSOX) regimen, and CTCs and cfDNA of the peripheral blood were detected before and after neoadjuvant therapy. Relationships between the number/type of CTC or cfDNA and the efficacy of neoadjuvant chemotherapy were analyzed. Results. Among 45 patients, 43 (95.6%) were positive, and the positive rate of mesenchymal CTC was increased with the increase in the T stage. The proportion of mesenchymal CTC was positively correlated with the N stage ( P < 0.05 ), and the larger N stage will have the higher proportion of mesenchymal CTC. Patients with a small number of mesenchymal CTC before neoadjuvant chemotherapy were more likely to achieve partial response (PR) with neoadjuvant therapy. Patients with positive CA-199 were more likely to achieve PR with neoadjuvant therapy ( P < 0.05 ). Patients in the PR group were more likely to have decreased/unchanged cfDNA concentration after neoadjuvant therapy ( P = 0.119 ). After neoadjuvant therapy (before surgery), the cfDNA concentration was higher and the efficacy of neoadjuvant therapy (SD or PD) was lower ( P = 0.045 ). Conclusions. Peripheral blood CTC, especially interstitial CTC and cfDNA, has a certain value in predicting the efficacy and prognosis of neoadjuvant chemotherapy in advanced gastric cancer.

Identification of Thrombosis-Related Genes in Patients with Advanced Gastric Cancer: Data from AGAMENON-SEOM Registry

Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic biomarkers. Therefore, our main objective was to identify genes related to thrombosis regardless of Lauren subtypes. Furthermore, in a secondary exploratory study, we seek to discover thrombosis-associated genes that were specific to each TCGA molecular subtype. We designed a nested case-control study using the cohort of the AGAMENON national advanced gastric cancer registry. Ninety-seven patients were selected—48 with and 49 without venous thromboembolism (using propensity score matching to adjust for confounding factors)—and a differential gene expression array stratified by Lauren histopathological subtypes was carried out in primary tumor samples. For the secondary objective, the aforementioned differential expression analysis was conducted for each TCGA group. Fifteen genes were determined to be associated with thrombosis with the same expression trend in both the intestinal and diffuse subtypes. In thrombotic subjects, CRELD1, KCNH8, CRYGN, MAGEB16, SAA1, ARL11, CCDC169, TRMT61A, RIPPLY3 and PLA2G6 were underexpressed (adjusted-p < 0.05), while PRKD3, MIR5683, SDCBP, EPS8 and CDC45 were overexpressed (adjusted-p < 0.05), and correlated, by logistic regression, with lower or higher thrombotic risk, respectively, in the overall cohort. In each TCGA molecular subtype, we identified a series of genes differentially expressed in thrombosis that appear to be subtype-specific. We have identified several genes associated with venous thromboembolism in advanced gastric cancer that are common to Lauren intestinal and diffuse subtypes. Should these genetic factors be validated in the future, they could be complemented with existing clinical models to bolster the ability to predict thrombotic risk in individuals with advanced gastric adenocarcinoma.

Association Between DCE-MRI Perfusion Histogram Parameters and EGFR and VEGF Expressions in Different Lauren Classifications of Advanced Gastric Cancer

Objective: To investigate the correlations between dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) perfusion histogram parameters and vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions in advanced gastric cancer (AGC).Methods: This retrospective study included 80 pathologically confirmed patients with AGC who underwent DCE-MRI before surgery from February 2017 to May 2021. The DCE-MRI perfusion histogram parameters were calculated by Omni Kinetics software in four quantitative parameter maps. Immunohistochemical methods were used to detect VEGF and EGFR expressions and calculate the immunohistochemical score.Results: VEGF expression was relatively lower in patients with intestinal-type AGC than those with diffuse-type AGC (p &lt; 0.05). For VEGF, Receiver operating characteristics (ROC) curve analysis revealed that Quantile 90 of Ktrans, Meanvalue of Kep and Quantile 50 of Ve provided the perfect combination of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for distinguishing high and low VEGF expression, For EGFR, Skewness of Ktrans, Energy of Kep and Entropy of Vp provided the perfect combination of sensitivity, specificity, PPV and NPV for distinguishing high and low EGFR expression. Ktrans (Quantile 90, Entropy) showed the strongest correlation with VEGF and EGFR in patients with intestinal-type AGC (r = 0.854 and r = 0.627, respectively); Ktrans (Mean value, Entropy) had the strongest correlation with VEGF and EGFR in patients with diffuse-type AGC (r = 0.635 and 0.656, respectively).Conclusion: DCE-MRI perfusion histogram parameters can serve as imaging biomarkers to reflect VEGF and EGFR expressions and estimate their difference in different Lauren classifications of AGC.