Analysis Of Clinical,pathological And Molecular Features In Prostate Small Cell Carcinoma

Objective:Small cell carcinoma of the prostate(SCCP)as a rare malignancy of the prostate.Clinical manifestations are usually insensitivity to hormone therapy,rapid disease progression,and a high susceptibility to distant metastases.Possible treatments for small cell carcinoma of the prostate are mainly chemotherapy and radiation therapy.However,there is no large sample case report on the therapeutic effect of these treatments on small cell carcinoma of the prostate.This has resulted in the effects of both treatments on survival prognosis remaining unknown.Therefore,in order to provide more scientific and reasonable individualized advice for this cancer patient,indepth analysis compared different treatments for SCCP,and looked for independent risk factors and genes associated with survival prognosis.Methods:Data on a total of 642 patients with SCCP were included from the Surveillance,Epidemiology and Outcomes(SEER)database.We estimated prognostic survival using the Kaplan-Meier method and analyzed prognostic risk factors associated with survival using a Cox risk regression model.Independent risk factors are used to construct a nomogram that predicts prognosis survival for patients at 1,2,and 3 years.Subsequently,mRNA expression data(16 small cell carcinomas and 16 advanced adenocarcinomas)from 32 prostate cancer samples were downloaded from the Gene Expression Comprehensive Database(GEO).Functional enrichment analysis was performed by R software screening differentially expressed genes and the DAVID database.The protein-protein interaction network(PPI)was constructed through Cytoscape to identify associated genes,and then targeted literature mining and search for genes related to radiation therapy for prostate cancer.Results:The median survival in people with SCCP in the SEER database is 9 months(95%CI,7 to 10 months).The most common distal metastatic organs are the bones,liver,and lungs.Radiotherapy was able to more significantly improve prognosis and prolong overall survival(P=0.0003),while chemotherapy had no statistically significant effect on overall survival(P=0.6374).In the univariate analysis,patient age,differentiation grade,TNM stage,AJCC 6th stage,combination therapy,and radiotherapy(P<0.05)all had a significant effect on overall survival.Further multivariate analysis revealed that patient age,differentiation grade and clinical stage were independent risk factors affecting prognosis.Subsequently,the nomogram was constructed to predict the survival rate of 1-,2-,and 3-year patients with SCCP.The Cindex and time AUC of the nomogram are 0.660 and>0.710,respectively.The calibration plots for predicting 1-and 3-year overall survival presented favorable consistencies between the nomogram prediction and actual observation.In addition,1034 differentially expressed genes were screened out in the GSE104786 dataset.Functional enrichment is mainly related to functions such as cell development,response to chemical and stimulus,and signal transmission.Finally,seven genes(AGR2,KLK2,SEL1L,URGCP,GRHL2,RGS10 and WDR62)associated with chemoradiotherapy efficacy were finally identified.For radiotherapy According to current research,patients with up-regulated genes AGR2,KLK2,URGCP,GRHL2 and RGS10 can prolong the corresponding progression-free survival after radiotherapy.For chemotherapy,patients with up-regulated SEL1L and down-regulated WDR62 may contribute to chemotherapy resistance.Conclusion:1.Age<65 years,low differentiated grade,AJCC 6th Ⅰ and Ⅱ stages,and radiotherapy were all associated with excellent survival prognosis for small prostate cell carcinoma.2.The nomogram based on R language can better predict the prognosis of small cell carcinoma of the prostate and provide help for clinical decision-making.3.Differentially expressed genes in prostate small cell carcinoma affect cell development,response to stimuli and signal transmission.Finally,seven genes that respond to radiotherapy and chemotherapy were identified,which may prolong the overall survival of patients by accelerating the hormone-DNA repair pathway and organelle degradation-related degradation pathways.This has a certain reference value for the decision-making of radiotherapy and chemotherapy for small cell carcinoma of prostate.