| BackgroundOesophageal Signet ring cell carcinoma is a rare pathological subtype of esophageal adenocarcinoma.Previous studies on signet ring cell carcinoma focused on gastric cancer,colorectal cancer and other tumors.There are few studies on signet ring cell carcinoma of the esophagus.Log odds of positive lymph nodes(LODDS)is a novel prognostic factor related to lymph nodes.This study is the first study to explore the log odds of positive lymph nodes(LODDS)as a prognostic factor in oesophageal signet ring cell carcinoma.Nomogram is a graphical result based on a multivariate analysis model.It has been widely used in cancer prognosis research.Based on this study,the prognostic prediction model for oesophageal signet ring cell carcinoma was constructed.ObjectiveThe purpose of this research was to explore a novel prognostic factor for oesophageal signet ring cell carcinoma by comparing two lymph node-related prognostic factors,log odds of positive lymph nodes(LODDS)and N stage.Then we construct a nomogram for predicting the outcome of signet ring cell carcinoma of oesophagus.MethodsA total of 259 cases of oesophageal signet ring cell carcinoma after oesophagectomy were obtained from the Surveillance,Epidemiology,and End Results database between 2006 and 2016.The prognostic values of LODDS and N stage for oesophageal signet ring cell carcinoma were evaluated by univariate and multivariate analyses.The Akaike information criterion(AIC)and the Harrell’s C-index were used to assess the value of two prediction models based on lymph nodes.A total of 968 cases of oesophageal signet ring cell carcinoma were extracted from the Surveillance,Epidemiology,and End Results(SEER)database between 2004 and 2016.Cases were divided into training cohort and validation cohort.Univariate and multivariable Cox analyses was performed to select the predictors of overall survival(OS)for the nomogram.The performance of nomogram was validated with Harrell’s concordance index(C-index),calibration curves and decision curve analysis(DCA).Results The 5-year cancer-specific survival(CSS)and 5-year overall survival(OS)rates of all the cases were 41.3%and 27.0%,respectively.The Kaplan-Meier method showed that LODDS had a higher score of log rank chi-squared(OS 46.162,CSS 41.178)than N stage(OS 36.215,CSS 31.583).Univariate analyses showed that insurance,race,T stage,M stage,TNM stage,radiation therapy,N stage and LODDS were potential prognostic factors for OS(p<0.1).The multivariate Cox regression model showed that LODDS was an significant independent prognostic factor for oesophageal signet ring carcinoma patients after surgical resection(P<0.05),while N stage was not considered to be a significant prognostic factor(P=0.122).Model 2(LODDS)had a higher degree of discrimination and fit than Model 1(N stage)(LODDS vs N stage,Harell’s C-index 0.673 vs 0.656,P<0.001;AIC 1688.824 vs 1697.519,P<0.001).For the part of nomogram of signet ring cell carcinoma,the independent prognostic factors for establishing the nomogram were marital status,invasion of the surrounding tissue,lymph node metastasis,distant metastasis,surgery and chemotherapy.The Harrell’s c-index value of the training cohort and validation cohort were 0.723 and 0.708.In the calibration curves,the predicted survival probability and the actual survival probability have a considerable consistency.Decision curve analysis(DCA)indicated the favourable potential clinical utility of the nomogram.ConclusionsLODDS is a superior prognostic factor for patients with oesophageal signet ring cell carcinoma after oesophagectomy than N stage.A nomogram to predict the overall survival(OS)of patients with oesophageal signet ring cell carcinoma was established.The validation of the nomogram fully demonstrates its great performance.BackgroundOesophageal cancer is currently the 9th most common cancer and the sixth most common cause of cancer death in the world.There are more and more molecular biology studies on esophageal cancer.The gene PGK1 corresponding to phosphoglycerate kinase 1(PGK1)has the characteristics of many oncogenes,so PGK1 has always been a research hotspot gene in the field of oncology.With the rise of tumor immunotherapy,more and more research focuses on tumor infiltrating immune cells.Among them,CD8+T cells,which are the main killer for tumors,have also been the research hotspot of tumor immunotherapy.ObjectiveThe purpose of this study is to study the value of PGK1 as a prognostic factor for oesophageal cancer and its relationship with tumor infiltrating CD8+T lymphocytesMethodsIn this study,a total of 100 tumor specimens that underwent oesophageal cancer resection at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences from 2005 to 2007 were collected.The specimens were immunohistochemically stained with PGK1 antibody and CD8 antibody.At the same time,the clinicopathological information of the corresponding patients was reviewed.Subsequently,public databases such as TCGA,TIMER,GEPIA were used to further verify the conclusions.Finally,the differentially expressed genes related to PGK1 in the TCGA database were enriched and analyzed to further explore the biological processes and related pathways of PGK1 in oesophageal cancer.ResultsThe Kaplan-Meier method was used in the enrolled medical records to draw a survival curve with PGK1 as a variable.It can be seen that the prognosis of the PGK1 high expression group is poor in the lower expression group.The COX hazard proportional regression model was used for univariate analysis of all variables included in the study,and it was found that age,N staging,TNM staging,and PGK1 were risk factors(P<0.1).They were included in the multivariate regression model for multivariate analysis,suggesting that PGK1 is Independent risk factors for esophageal cancer(P<0.05).The Fisher’s exact test was used to analyze the correlation between PGK1 expression and CD8+lymphocyte infiltration,and the calculated P value was 0.031(P<0.05),and the Pearson correlation coefficient was-0.192,considering that there is a statistically significant negative correlation between PGK1 expression and CD8+lymphocyte infiltration.After verifying the above conclusions in TIMER,a consistent conclusion was reached.After enrichment analysis,the KEGG pathways that are most involved in PGK1 related genes include cell cycle,purine metabolism,glycolysis/gluconeogenesis,amino acid biosynthesis and other pathways.The most relevant biological processes in GO analysis include:organelle division,DNA conformational changes,cell nuclear division,cell cycle mitosis.There are many cytological components in GO analysis,including:chromosome regions,spindles,centrosomes.The molecular functions involved in GO analysis include ATPase activation,ATPase activation coupling,and cadherin binding.ConclusionsPGK1 can be used as a prognostic predictor of esophageal cancer.The high expression of PGK1 indicates the poor prognosis of esophageal cancer.In addition,the expression of PGK1 in esophageal cancer is negatively correlated with tumor infiltrating CD8+lymphocytes. |
PDF Full Text Request