The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer
The impact of germline variants on the regulation of the expression of tumor microenvironment (TME)-based immune response genes remains unclear. Expression quantitative trait loci (eQTL) provide insight into the effect of downstream target genes (eGenes) regulated by germline-associated variants (eV...
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MDPI AG
2022-01-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/2/315 |
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| author | Ren-Hao Chan Po-Chuan Chen Yu-Min Yeh Bo-Wen Lin Kai-Di Yang Meng-Ru Shen Peng-Chan Lin |
| author_facet | Ren-Hao Chan Po-Chuan Chen Yu-Min Yeh Bo-Wen Lin Kai-Di Yang Meng-Ru Shen Peng-Chan Lin |
| author_sort | Ren-Hao Chan |
| collection | DOAJ |
| description | The impact of germline variants on the regulation of the expression of tumor microenvironment (TME)-based immune response genes remains unclear. Expression quantitative trait loci (eQTL) provide insight into the effect of downstream target genes (eGenes) regulated by germline-associated variants (eVariants). Through eQTL analyses, we illustrated the relationships between germline eVariants, TME-based immune response eGenes, and clinical outcomes. In this study, both RNA sequencing data from primary tumor and germline whole-genome sequencing data were collected from patients with stage III colorectal cancer (CRC). Ninety-nine high-risk subjects were subjected to immune response gene expression analyses. Seventy-seven subjects remained for further analysis after quality control, of which twenty-two patients (28.5%) experienced tumor recurrence. We found that 65 eQTL, including 60 germline eVariants and 22 TME-based eGenes, impacted the survival of cancer patients. For the recurrence prediction model, 41 differentially expressed genes (DEGs) achieved the best area under the receiver operating characteristic curve of 0.93. In total, 19 survival-associated eGenes were identified among the DEGs. Most of these genes were related to the regulation of lymphocytes and cytokines. A high expression of <i>HGF</i>, <i>CCR5</i>, <i>IL18</i>, <i>FCER1G</i>, <i>TDO2</i>, <i>IFITM2</i>, and <i>LAPTM5</i> was significantly associated with a poor prognosis. In addition, the <i>FCER1G</i> eGene was associated with tumor invasion, tumor nodal stage, and tumor site. The eVariants that regulate the TME-based expression of <i>FCER1G</i>, including rs2118867 and rs12124509, were determined to influence survival and chromatin binding preferences. We also demonstrated that <i>FCER1G</i> and co-expressed genes in TME were related to the aggregation of leukocytes via pathway analysis. By analyzing the eQTL from the cancer genome using germline variants and TME-based RNA sequencing, we identified the eQTL in immune response genes that impact colorectal cancer characteristics and survival. |
| first_indexed | 2024-03-09T22:12:07Z |
| format | Article |
| id | doaj.art-3880b854ef9c4e3ebff9a99894d54194 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T22:12:07Z |
| publishDate | 2022-01-01 |
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| spelling | doaj.art-3880b854ef9c4e3ebff9a99894d541942023-11-23T19:29:59ZengMDPI AGDiagnostics2075-44182022-01-0112231510.3390/diagnostics12020315The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal CancerRen-Hao Chan0Po-Chuan Chen1Yu-Min Yeh2Bo-Wen Lin3Kai-Di Yang4Meng-Ru Shen5Peng-Chan Lin6Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanDepartment of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanDepartment of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanDepartment of Computer Science and Information Engineering, College of Electrical Engineering and Computer Science, National Cheng Kung University, Tainan 704, TaiwanDepartment of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, TaiwanThe impact of germline variants on the regulation of the expression of tumor microenvironment (TME)-based immune response genes remains unclear. Expression quantitative trait loci (eQTL) provide insight into the effect of downstream target genes (eGenes) regulated by germline-associated variants (eVariants). Through eQTL analyses, we illustrated the relationships between germline eVariants, TME-based immune response eGenes, and clinical outcomes. In this study, both RNA sequencing data from primary tumor and germline whole-genome sequencing data were collected from patients with stage III colorectal cancer (CRC). Ninety-nine high-risk subjects were subjected to immune response gene expression analyses. Seventy-seven subjects remained for further analysis after quality control, of which twenty-two patients (28.5%) experienced tumor recurrence. We found that 65 eQTL, including 60 germline eVariants and 22 TME-based eGenes, impacted the survival of cancer patients. For the recurrence prediction model, 41 differentially expressed genes (DEGs) achieved the best area under the receiver operating characteristic curve of 0.93. In total, 19 survival-associated eGenes were identified among the DEGs. Most of these genes were related to the regulation of lymphocytes and cytokines. A high expression of <i>HGF</i>, <i>CCR5</i>, <i>IL18</i>, <i>FCER1G</i>, <i>TDO2</i>, <i>IFITM2</i>, and <i>LAPTM5</i> was significantly associated with a poor prognosis. In addition, the <i>FCER1G</i> eGene was associated with tumor invasion, tumor nodal stage, and tumor site. The eVariants that regulate the TME-based expression of <i>FCER1G</i>, including rs2118867 and rs12124509, were determined to influence survival and chromatin binding preferences. We also demonstrated that <i>FCER1G</i> and co-expressed genes in TME were related to the aggregation of leukocytes via pathway analysis. By analyzing the eQTL from the cancer genome using germline variants and TME-based RNA sequencing, we identified the eQTL in immune response genes that impact colorectal cancer characteristics and survival.https://www.mdpi.com/2075-4418/12/2/315expression quantitative trait locitumor microenvironnementimmune response genes<i>FCER1G</i>colorectal cancer |
| spellingShingle | Ren-Hao Chan Po-Chuan Chen Yu-Min Yeh Bo-Wen Lin Kai-Di Yang Meng-Ru Shen Peng-Chan Lin The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer Diagnostics expression quantitative trait loci tumor microenvironnement immune response genes <i>FCER1G</i> colorectal cancer |
| title | The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer |
| title_full | The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer |
| title_fullStr | The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer |
| title_full_unstemmed | The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer |
| title_short | The Expression Quantitative Trait Loci in Immune Response Genes Impact the Characteristics and Survival of Colorectal Cancer |
| title_sort | expression quantitative trait loci in immune response genes impact the characteristics and survival of colorectal cancer |
| topic | expression quantitative trait loci tumor microenvironnement immune response genes <i>FCER1G</i> colorectal cancer |
| url | https://www.mdpi.com/2075-4418/12/2/315 |
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