PurposeThis clinical study sought to determine whether the levels of inflammatory markers predicted the survival of advanced gastric cancer (AGC) patients who underwent anti-programmed death 1 (PD-1) therapy.MethodsUsing AGC patient plasma samples and baseline characteristics, we investigated the specific value of inflammatory markers in AGC from a clinical perspective in immunotherapy.ResultsOne hundred and six patients with AGC who underwent anti-PD-1 therapy were enrolled in this study between 20 July 2019 and 16 March 2021. A significant decrease in NLR, dNLR, and SII was noticed among the PR (P=0.023; P=0.036; P=0.001), SD (P=0.048; P=0.022; P=0.023), ORR (P=0.021; P=0.032; P=0.001), and DCR (P=0.003; P=0.001; P<0.001) groups after anti-PD-1 therapy. Additionally, a significant decline of PLR was also observed in PR (P=0.010), ORR (P=0.007), and DCR (P=0.005) after anti-PD-1 therapy. Only MLR levels increased significantly at the time of anti-PD-1 immunotherapy the failure compared to baseline (P=0.039). And statistically significant elevations in NLR (P=0.001), MLR (P=0.020), dNLR (P=0.002), and SII (P=0.019) were found in failure of anti-PD-1 treatment compared to optimal efficacy in AGC patients. In first-line treatment, the number of metastatic sites (P=0.001) was an independent prognostic factor for PFS, and peritoneal metastases (P=0.004) and platelet-to-lymphocyte ratio (PLR) level (P=0.014) were independent prognostic predictors of OS according to Cox regression analysis. In second-line or posterior treatment, the number of metastatic sites (P=0.007), ECOG (P=0.011), and PLR level (P=0.033) were independent prognostic factors for PFS in AGC patients, and the number of metastatic sites (P=0.003), differentiation (P=0.030), and NLR level (P<0.001) were independent prognostic factors for OS according to Cox regression analysis.ConclusionsNLR, PLR, MLR, dNLR, and SII can reflect the short-term efficacy of immunotherapy in patients who underwent anti-PD-1 therapy with AGC. PLR is an independent prognostic factor for OS in AGC patients receiving first-line immunotherapy and PFS in those receiving second-line or posterior immunotherapy. And NLR was an independent prognostic factor for OS in AGC patients receiving second-line or posterior immunotherapy. The number of metastatic sites was significantly associated with the prognosis of AGC patients who received immunotherapy.

Background: Neutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients' prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis. Methods: We obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO-Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis. Results: Seven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p<0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006). Conclusion:Overall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.

PurposeThis study aims to assess the prognostic value of inflammatory markers and clinical features in advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients receiving anti-programmed death 1 (PD-1) treatment.MethodsBased on receiver operating characteristic curve (ROC) analysis, Youden’s indexes were applied to determine the cut-off values for inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocye ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Wilcoxon test was conducted to evaluate the changes in above inflammatory markers. Kaplan-Meier method was utilized to estimate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used to compare the different survival between groups. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of inflammatory markers and clinical features.Results162 advanced or metastatic ESCC patients receiving anti-PD-1 treatment were enrolled in this retrospective study. The cut-off values of NLR, dNLR, MLR, PLR, and SII were 4.748, 2.214, 0.309, 250.505, and 887.895, respectively. NLR, dNLR, PLR, and SII declined significantly among the partial response (PR) (P&lt;0.001, P&lt;0.001, P=0.036, P&lt;0.001), objective response rate (ORR) (P&lt;0.001, P&lt;0.001, P=0.036, P&lt;0.001), and disease control rate (DCR) (P&lt;0.001, P&lt;0.001, P=0.038, P&lt;0.001) groups, respectively. Significant increases were found in NLR (P&lt;0.001), dNLR (P&lt;0.001), MLR (P=0.001), and SII (P=0.024) when anti-PD-1 treatment failed. Multivariate Cox regression analysis indicated that NLR (P&lt;0.001, P=0.002), lymph node metastasis (P=0.013, P=0.001), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P=0.008, P=0.002), and treatment lines (P=0.037, P=0.048) were significant prognostic indicators of PFS and OS. Additionally, SII (P=0.016) was also significantly related to OS in ESCC patients. The risk score model showed that low risk patients prolonged PFS and OS than those with middle or high risk (P&lt;0.001, P&lt;0.001).ConclusionInflammatory markers can reflect short-term outcomes of anti-PD-1 treatment for ESCC patients. NLR, lymph node metastases, ECOG PS, and treatment lines are significant prognostic indicators for PFS and OS. And the risk score model constructed based on the above factors has favourable prognostic predictive value.