Mei Ding , Jianchao Gao , Jinyan Wang , Zongfu Li , Xiangliang Gong , Zhiyu Cui , Changjun Li , Hongjun Xue , Dandan Li , Yigang Wang
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Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database.</p></div><div><h3>Results</h3><p>Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (<em>p</em> < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (<em>p</em> < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (<em>p</em> < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (<em>p</em> < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC.</p></div><div><h3>Conclusion</h3><p>NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.</p></div>","PeriodicalId":48674,"journal":{"name":"Arab Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Colorectal cancer subtyping and immune landscape analysis based on natural killer cell-related genes\",\"authors\":\"Mei Ding , Jianchao Gao , Jinyan Wang , Zongfu Li , Xiangliang Gong , Zhiyu Cui , Changjun Li , Hongjun Xue , Dandan Li , Yigang Wang\",\"doi\":\"10.1016/j.ajg.2024.03.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and study aims</h3><p>The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes.</p></div><div><h3>Patients/material and methods</h3><p>mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database.</p></div><div><h3>Results</h3><p>Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (<em>p</em> < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (<em>p</em> < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (<em>p</em> < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (<em>p</em> < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. 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引用次数: 0
摘要
研究背景和目的:结直肠癌(CRC)的预后与自然杀伤细胞(NK)有关,但基于NK细胞的CRC分子亚型特征尚不清楚。本研究旨在确定与NK细胞相关的CRC分子亚型,并分析不同亚型患者的生存状况和免疫格局。患者/材料和方法:从癌症基因组图谱(The Cancer Genome Atlas)中获取CRC患者的mRNA表达数据、单核苷酸变异(SNV)数据和临床信息。通过差异分析获得差异表达基因(DEGs),并与NK细胞相关基因相交,得到103个NK细胞相关的CRC DEGs(NCDEGs)。根据 NCDEGs,通过无监督聚类分析将 CRC 样本分为三组。此外,还进行了生存分析、免疫分析、基因组富集分析(Gene Set Enrichment Analysis,GSEA)和肿瘤突变负荷分析(Tumor mutation burden,TMB)。最后,利用 CMap 数据库筛选了与 NCDEG 相关的小分子药物:结果:生存率分析表明,群组2的生存率低于群组1和群组3(p 结论:群组2的生存率低于群组1和群组3):NK细胞相关的CRC亚型可用于评估CRC患者的肿瘤特征,为CRC患者提供重要参考。
Colorectal cancer subtyping and immune landscape analysis based on natural killer cell-related genes
Background and study aims
The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes.
Patients/material and methods
mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database.
Results
Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (p < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (p < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (p < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (p < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC.
Conclusion
NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.
期刊介绍:
Arab Journal of Gastroenterology (AJG) publishes different studies related to the digestive system. It aims to be the foremost scientific peer reviewed journal encompassing diverse studies related to the digestive system and its disorders, and serving the Pan-Arab and wider community working on gastrointestinal disorders.