Background Relapsed soft tissue sarcomas(STS)have poor prognosis and limited treatment options.However,the molecular mechanism underlying recurrence and the prognostic predictor for STS are unclear.Methods We enrolled...Background Relapsed soft tissue sarcomas(STS)have poor prognosis and limited treatment options.However,the molecular mechanism underlying recurrence and the prognostic predictor for STS are unclear.Methods We enrolled 35 extremity and trunk STS patients.Tumor specimens of 20 relapsed and 15 primary STS underwent sequencing to detect DNA mutation,RNA expression,and DNA methylation.Moreover,206 STS cases from The Cancer Genome Atlas(TCGA)were utilized to construct the relapse-associated risk score model(RRSM),validated using three Gene Expression Omnibus datasets.Key model genes,COL6A3,FZD7,ITPKA,and PRKAG1,were validated in formalin-fixed paraffin-embedded tissue sections from primary and relapsed STS patients,confirming their potential involvement in STS recurrence.Results The primary STS exhibited an immune-enriched tumor microenvironment,whereas the tumor microenvironment of relapsed STS had features that promote tumor recurrence or metastasis.The RRSM could predict relapse-free survival in TCGA STS and performed well in the validation cohort.Multivariate analysis revealed that RRSM was an independent prognostic factor.Moreover,the nomogram developed had excellent predictive ability.Conclusions This study revealed different multi-omic profiles between relapsed and primary STS.RRSM is a potential prognostic predictor for STS and lays a foundation for early intervention of high-risk STS patients.The expression of genes FZD7,ITPKA,and PRKAG1 may guide STS treatment decisions.展开更多
基金supported by the Clinical Research Project of The First Hospital of Jilin University in 2024(grant No.JDYYLCYJ-20240004)the National Key Research and development Program of China(grant No.2022YFC2405805)the National Natural Science Foundation of China(grant No.U23A20490).
文摘Background Relapsed soft tissue sarcomas(STS)have poor prognosis and limited treatment options.However,the molecular mechanism underlying recurrence and the prognostic predictor for STS are unclear.Methods We enrolled 35 extremity and trunk STS patients.Tumor specimens of 20 relapsed and 15 primary STS underwent sequencing to detect DNA mutation,RNA expression,and DNA methylation.Moreover,206 STS cases from The Cancer Genome Atlas(TCGA)were utilized to construct the relapse-associated risk score model(RRSM),validated using three Gene Expression Omnibus datasets.Key model genes,COL6A3,FZD7,ITPKA,and PRKAG1,were validated in formalin-fixed paraffin-embedded tissue sections from primary and relapsed STS patients,confirming their potential involvement in STS recurrence.Results The primary STS exhibited an immune-enriched tumor microenvironment,whereas the tumor microenvironment of relapsed STS had features that promote tumor recurrence or metastasis.The RRSM could predict relapse-free survival in TCGA STS and performed well in the validation cohort.Multivariate analysis revealed that RRSM was an independent prognostic factor.Moreover,the nomogram developed had excellent predictive ability.Conclusions This study revealed different multi-omic profiles between relapsed and primary STS.RRSM is a potential prognostic predictor for STS and lays a foundation for early intervention of high-risk STS patients.The expression of genes FZD7,ITPKA,and PRKAG1 may guide STS treatment decisions.
