This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion throug...This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.展开更多
目的:研究CLEC11A基因在结直肠癌患(CRC)者中的表达差异及临床意义,寻求结直肠癌筛查治疗新靶点。方法:基于TIMER2.0数据库、UALCAN数据库、GEPIA2.0数据库在线分析CLEC11A在泛癌中表达差异;进一步展开生存预后分析、临床病理特征分析...目的:研究CLEC11A基因在结直肠癌患(CRC)者中的表达差异及临床意义,寻求结直肠癌筛查治疗新靶点。方法:基于TIMER2.0数据库、UALCAN数据库、GEPIA2.0数据库在线分析CLEC11A在泛癌中表达差异;进一步展开生存预后分析、临床病理特征分析、免疫浸润、甲基化、富集分析等深入探讨CLEC11A与CRC发生转归间潜在联系。结果:CLEC11A在CRC中较正常组织高度表达,与患者预后呈负相关。CLEC11A与CD8+ T细胞、CD4+ T细胞、巨噬细胞、中性粒细胞的浸润水平呈正相关,与B细胞的浸润水平呈负相关。CLEC11A甲基化水平同CRC患者年龄存在显著相关性。GO与KEGG富集分析显示共表达基因在伤口愈合、自噬调节、细胞外基质组成及癌症的转录失调等多方面富集。结论:CLEC11A与CRC不良预后密切相关,可能是CRC潜在诊疗靶点。Objectives: To study the expression differences and clinical significance of the CLEC11A gene in patients with colorectal cancer (CRC) and seek new targets for CRC screening and treatment. Methods: Based on the TIMER2.0 database, UALCAN database, and GEPIA2.0 database, the expression differences of CLEC11A in pan-cancers were analyzed online. Survival prognosis analysis, clinicopathological feature analysis, immune infiltration, methylation, and enrichment analysis were further carried out to deeply explore the potential connection between CLEC11A and the occurrence and prognosis of CRC. Results: CLEC11A was highly expressed in CRC compared with normal tissues and was negatively correlated with the prognosis of patients. CLEC11A was positively correlated with the infiltration levels of CD8+ T cells, CD4+ T cells, macrophages, and neutrophils, and negatively correlated with the infiltration level of B cells. The methylation level of CLEC11A was significantly correlated with the age of CRC patients. GO and KEGG enrichment analyses showed that the co-expressed genes were enriched in multiple aspects such as wound healing, autophagy regulation, extracellular matrix composition, and transcriptional dysregulation in cancer. Conclusion: CLEC11A is closely related to the poor prognosis of CRC and may be a potential diagnosis and treatment target for CRC.展开更多
文摘This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.
文摘目的:研究CLEC11A基因在结直肠癌患(CRC)者中的表达差异及临床意义,寻求结直肠癌筛查治疗新靶点。方法:基于TIMER2.0数据库、UALCAN数据库、GEPIA2.0数据库在线分析CLEC11A在泛癌中表达差异;进一步展开生存预后分析、临床病理特征分析、免疫浸润、甲基化、富集分析等深入探讨CLEC11A与CRC发生转归间潜在联系。结果:CLEC11A在CRC中较正常组织高度表达,与患者预后呈负相关。CLEC11A与CD8+ T细胞、CD4+ T细胞、巨噬细胞、中性粒细胞的浸润水平呈正相关,与B细胞的浸润水平呈负相关。CLEC11A甲基化水平同CRC患者年龄存在显著相关性。GO与KEGG富集分析显示共表达基因在伤口愈合、自噬调节、细胞外基质组成及癌症的转录失调等多方面富集。结论:CLEC11A与CRC不良预后密切相关,可能是CRC潜在诊疗靶点。Objectives: To study the expression differences and clinical significance of the CLEC11A gene in patients with colorectal cancer (CRC) and seek new targets for CRC screening and treatment. Methods: Based on the TIMER2.0 database, UALCAN database, and GEPIA2.0 database, the expression differences of CLEC11A in pan-cancers were analyzed online. Survival prognosis analysis, clinicopathological feature analysis, immune infiltration, methylation, and enrichment analysis were further carried out to deeply explore the potential connection between CLEC11A and the occurrence and prognosis of CRC. Results: CLEC11A was highly expressed in CRC compared with normal tissues and was negatively correlated with the prognosis of patients. CLEC11A was positively correlated with the infiltration levels of CD8+ T cells, CD4+ T cells, macrophages, and neutrophils, and negatively correlated with the infiltration level of B cells. The methylation level of CLEC11A was significantly correlated with the age of CRC patients. GO and KEGG enrichment analyses showed that the co-expressed genes were enriched in multiple aspects such as wound healing, autophagy regulation, extracellular matrix composition, and transcriptional dysregulation in cancer. Conclusion: CLEC11A is closely related to the poor prognosis of CRC and may be a potential diagnosis and treatment target for CRC.
