objective:Inflammatory response plays a crucial role in the development and treatment of cancer.However,the role of inflammatory response in triple-negative breast cancer(TNBC)remains unclear.Based on the heterogeneit...objective:Inflammatory response plays a crucial role in the development and treatment of cancer.However,the role of inflammatory response in triple-negative breast cancer(TNBC)remains unclear.Based on the heterogeneity of the inflammatory response,we classified TNBC,elucidated its subtype features,and revealed potential therapeutic strategies.Methods:We established inflammatory response subtyping based on the RNA sequencing data of TNBCs derived from a cohort at the Fudan University Shanghai Cancer Center(FUSCC).Next,we explored the features and potential therapeutic strategies for each subgroup by analyzing transcriptome data.Using a machine-learning method,we validated and generalized the TNBC inflammatory response subtypes in an external dataset.Results:A total of 360 TNBC samples and 88 normal tissues were collected from a cohort at FUSCC.Patients with TNBC were divided into four inflammatory response groups(IRGs)based on the expression of inflammatory response genes:high inflammatory response gene expression with pronounced pyroptosis phenotype and high immune cellinfiltration(IRG 1),low inflammatory response gene expression and low immune cell infiltration(IRG 2),ITGB8 specific inflammatory response with a predominant proliferation phenotype(IRG 3),and low M1/M2 ratio with a marked angiogenesis phenotype(IRG 4).Relapse-free survival(RFS)was better in iRG 1 and 2 and worse in IRG 3 and 4.Owing to their poor prognosis,we mainly focused on IRG 3 and IRG 4 to investigate potential treatment strategies.ITGB8 was highly expressed in IRG 3;thus,targeting ITGB8 may be a potential therapeutic strategy for patients in IRG 3.IRG 4 had a lower M1/M2 ratio and a marked angiogenesis phenotype;therefore,therapeutic strategies,such as anti-angiogenesis or M2 to M1 repolarization of macrophages,could be recommended for these patients.Additionally,we validated and generalized the TNBC inflammatory response subtyping in an external dataset using a machine-learning method.Conclusion:TNBC patients with different inflammatory response subtypes have different characteristics and may need subtype-specific treatment strategies.展开更多
文摘objective:Inflammatory response plays a crucial role in the development and treatment of cancer.However,the role of inflammatory response in triple-negative breast cancer(TNBC)remains unclear.Based on the heterogeneity of the inflammatory response,we classified TNBC,elucidated its subtype features,and revealed potential therapeutic strategies.Methods:We established inflammatory response subtyping based on the RNA sequencing data of TNBCs derived from a cohort at the Fudan University Shanghai Cancer Center(FUSCC).Next,we explored the features and potential therapeutic strategies for each subgroup by analyzing transcriptome data.Using a machine-learning method,we validated and generalized the TNBC inflammatory response subtypes in an external dataset.Results:A total of 360 TNBC samples and 88 normal tissues were collected from a cohort at FUSCC.Patients with TNBC were divided into four inflammatory response groups(IRGs)based on the expression of inflammatory response genes:high inflammatory response gene expression with pronounced pyroptosis phenotype and high immune cellinfiltration(IRG 1),low inflammatory response gene expression and low immune cell infiltration(IRG 2),ITGB8 specific inflammatory response with a predominant proliferation phenotype(IRG 3),and low M1/M2 ratio with a marked angiogenesis phenotype(IRG 4).Relapse-free survival(RFS)was better in iRG 1 and 2 and worse in IRG 3 and 4.Owing to their poor prognosis,we mainly focused on IRG 3 and IRG 4 to investigate potential treatment strategies.ITGB8 was highly expressed in IRG 3;thus,targeting ITGB8 may be a potential therapeutic strategy for patients in IRG 3.IRG 4 had a lower M1/M2 ratio and a marked angiogenesis phenotype;therefore,therapeutic strategies,such as anti-angiogenesis or M2 to M1 repolarization of macrophages,could be recommended for these patients.Additionally,we validated and generalized the TNBC inflammatory response subtyping in an external dataset using a machine-learning method.Conclusion:TNBC patients with different inflammatory response subtypes have different characteristics and may need subtype-specific treatment strategies.
