Colorectal cancer(CRC)is the third most common cancer worldwide and the second leading cause of cancer-related mortality.While early-stage CRC patients generally exhibit favorable overall survival(OS)rates,the prognos...Colorectal cancer(CRC)is the third most common cancer worldwide and the second leading cause of cancer-related mortality.While early-stage CRC patients generally exhibit favorable overall survival(OS)rates,the prognosis for metastatic CRC(mCRC)remains poor,with a survival rate<15%.Targeted combination therapy remains the main treatment strategy for mCRC,with a median OS(mOS)of only 25-30 months.展开更多
Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene expression.Methods:For this study,623 samples were ...Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene expression.Methods:For this study,623 samples were collected from The Cancer Genome Atlas(TCGA)database,comprising tumor mutational burden(TMB),RNA sequencing(RNA-Seq),and clinical data.Differential gene expression analysis,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified genes were conducted using the R package.Additionally,a comparative analysis of immune infiltrating cell composition in metastatic and non-metastatic groups was performed.Hub genes,exhibiting high levels of interaction,were selected using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database.The Drug Gene Interaction Database(DGIdb)was then utilized to estimate drugs targeting the identified hub genes.Results:The transcriptome data of 326 colorectal cancer patients with low TMB were analyzed,comprising 58 patients with metastasis and 268 patients without metastasis.Among the differential expression in 1,111 genes for patients with metastasis compared to those without metastasis,733 genes were upregulated,and 378 genes were downregulated.KEGG and GO enrichment analysis indicated significant differences in gene expression in CRC metastatic patients with low TMB compared to non-metastasis patients with low TMB.Enriched pathways included humoral immune response,immunoglobulin production,and regulation of AMPA receptor activity.Two genes related to interleukin-12 were identified through secondary enrichment for immune-related genes.Analysis of tumor-infiltrating immune cell data revealed significant differences in memory-activated T cell CD4 and T cell CD8.Conclusions:This analysis of RNA sequencing data and immune-filtrating cell data revealed significant differences between metastatic colorectal cancer patients with low TMB and their non-metastatic counterparts.These distinctions suggest the possibility of identifying more effective drugs or therapies for metastatic colorectal cancer patients with low TMB.展开更多
目的:在抗体偶联药物(antibody drug conjugate,ADC)逐渐兴起的背景下,基于Hofmann标准与HERACLES标准,评估转移性结直肠癌(metastatic colorectal cancer,mCRC)中HER-2表达及临床意义。方法:回顾性收集2011年1月至2013年12月在天津医...目的:在抗体偶联药物(antibody drug conjugate,ADC)逐渐兴起的背景下,基于Hofmann标准与HERACLES标准,评估转移性结直肠癌(metastatic colorectal cancer,mCRC)中HER-2表达及临床意义。方法:回顾性收集2011年1月至2013年12月在天津医科大学肿瘤医院经明确病理诊断的mCRC患者的转移灶(105例)及对应原发灶组织(70例),应用两种标准对HER-2进行三分类(HER-20、HER-2低表达和HER-2阳性)评估,比较两种标准的一致性及配对转移灶与原发灶的一致性,并分析HER-2表达与临床病理因素的相关性。结果:基于两种标准,mCRC转移灶中HER-2阳性率均为3.8%(4/105),原发灶中的HER-2阳性率分别为7.1%(5/70)和5.7%(4/70)。不论原发灶还是转移灶,Hofmann标准对HER-2低表达患者的检出率均高于HERACLES标准(28.6%vs.25.7%;20.0%vs.11.4%)。两种标准评估HER-2表达的一致性较好(kappa=0.828)。不论基于何种评价标准,原发灶和转移灶中HER-2表达存在差异性(差异率28.6%)。结论:本研究发现m CRC中HER-2阳性及HER-2低表达在转移灶与原发灶之间均存在差异性,建议临床可以同时检测以提高检出率。Hofmann标准对HER-2低表达患者检出率高于HERACLES标准,鉴于目前对于CRC中HER-2表达尚无统一判读标准,ADC药物的临床疗效与不同判读标准下HER-2表达的关系还需要进一步大样本、多中心研究。展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.U22A20330 and 82373372)the Key Project of Research and Development Plan in Heilongjiang Province(Nos.2022ZX06C01 and JD2023SJ40)+1 种基金the Natural Science Funding of Heilongjiang(No.YQ2022H017)the Haiyan Foundation of Harbin Medical University Cancer Hospital(No.JJJQ 2024-02).
文摘Colorectal cancer(CRC)is the third most common cancer worldwide and the second leading cause of cancer-related mortality.While early-stage CRC patients generally exhibit favorable overall survival(OS)rates,the prognosis for metastatic CRC(mCRC)remains poor,with a survival rate<15%.Targeted combination therapy remains the main treatment strategy for mCRC,with a median OS(mOS)of only 25-30 months.
文摘Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene expression.Methods:For this study,623 samples were collected from The Cancer Genome Atlas(TCGA)database,comprising tumor mutational burden(TMB),RNA sequencing(RNA-Seq),and clinical data.Differential gene expression analysis,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified genes were conducted using the R package.Additionally,a comparative analysis of immune infiltrating cell composition in metastatic and non-metastatic groups was performed.Hub genes,exhibiting high levels of interaction,were selected using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database.The Drug Gene Interaction Database(DGIdb)was then utilized to estimate drugs targeting the identified hub genes.Results:The transcriptome data of 326 colorectal cancer patients with low TMB were analyzed,comprising 58 patients with metastasis and 268 patients without metastasis.Among the differential expression in 1,111 genes for patients with metastasis compared to those without metastasis,733 genes were upregulated,and 378 genes were downregulated.KEGG and GO enrichment analysis indicated significant differences in gene expression in CRC metastatic patients with low TMB compared to non-metastasis patients with low TMB.Enriched pathways included humoral immune response,immunoglobulin production,and regulation of AMPA receptor activity.Two genes related to interleukin-12 were identified through secondary enrichment for immune-related genes.Analysis of tumor-infiltrating immune cell data revealed significant differences in memory-activated T cell CD4 and T cell CD8.Conclusions:This analysis of RNA sequencing data and immune-filtrating cell data revealed significant differences between metastatic colorectal cancer patients with low TMB and their non-metastatic counterparts.These distinctions suggest the possibility of identifying more effective drugs or therapies for metastatic colorectal cancer patients with low TMB.
