Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer
Abstract Background To investigate the association between computed tomography (CT)-detected extramural venous invasion (EMVI)-related genes and immunotherapy resistance and immune escape in patients with gastric cancer (GC). Methods Thirteen patients with pathologically proven locally advanced GC w...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03845-2 |
| _version_ | 1797958482808274944 |
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| author | Hao Yang Xinyi Gou Caizhen Feng Yinli Zhang Fan Chai Nan Hong Yingjiang Ye Yi Wang Bo Gao Jin Cheng |
| author_facet | Hao Yang Xinyi Gou Caizhen Feng Yinli Zhang Fan Chai Nan Hong Yingjiang Ye Yi Wang Bo Gao Jin Cheng |
| author_sort | Hao Yang |
| collection | DOAJ |
| description | Abstract Background To investigate the association between computed tomography (CT)-detected extramural venous invasion (EMVI)-related genes and immunotherapy resistance and immune escape in patients with gastric cancer (GC). Methods Thirteen patients with pathologically proven locally advanced GC who had undergone preoperative abdominal contrast-enhanced CT and radical resection surgery were included in this study. Transcriptome sequencing was multidetector performed on the cancerous tissue obtained during surgery, and EMVI-related genes (P value for association < 0.001) were selected. A single-sample gene set enrichment analysis algorithm was also used to divide all GC samples (n = 377) in The Cancer Genome Atlas (TCGA) database into high and low EMVI-immune related groups based on immune-related differential genes. Cluster analysis was used to classify EMVI-immune-related genotypes, and survival among patients was validated in TCGA and Gene Expression Omnibus (GEO) cohorts. The EMVI scores were calculated using principal component analysis (PCA), and GC samples were divided into high and low EMVI score groups. Microsatellite instability (MSI) status, tumor mutation burden (TMB), response rate to immune checkpoint inhibitors (ICIs), immune escape were compared between the high and low EMVI score groups. Hub gene of the model in pan-cancer analysis was also performed. Results There were 17 EMVI-immune-related genes used for cluster analysis. PCA identified 8 genes (PCH17, SEMA6B, GJA4, CD34, ACVRL1, SOX17, CXCL12, DYSF) that were used to calculate EMVI scores. High EMVI score groups had lower MSI, TMB and response rate of ICIs, status but higher immune escape status. Among the 8 genes used for EMVI scores, CXCL12 and SOX17 were at the core of the protein–protein interaction (PPI) network and had a higher priority in pan-cancer analysis. Immunohistochemical analysis showed that the expression of CXCL12 and SOX17 was significantly higher in CT-detected EMVI-positive samples than in EMVI-negative samples (P < 0.0001). Conclusion A CT-detected EMVI gene signature could be a potential negative biomarker for ICIs treatment, as the signature is negatively correlated with TMB, and MSI, resulting in poorer prognosis. |
| first_indexed | 2024-04-11T00:20:45Z |
| format | Article |
| id | doaj.art-6950291410f24c9287702066c3ee0aee |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T00:20:45Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-6950291410f24c9287702066c3ee0aee2023-01-08T12:19:28ZengBMCJournal of Translational Medicine1479-58762023-01-0121111710.1186/s12967-022-03845-2Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancerHao Yang0Xinyi Gou1Caizhen Feng2Yinli Zhang3Fan Chai4Nan Hong5Yingjiang Ye6Yi Wang7Bo Gao8Jin Cheng9Department of General Surgery, The Second Affiliated Hospital of Harbin Medical UniversityDepartment of Radiology, Peking University People’s HospitalDepartment of Radiology, Peking University People’s HospitalDepartment of Pathology, Peking University People’s HospitalDepartment of Radiology, Peking University People’s HospitalDepartment of Radiology, Peking University People’s HospitalDepartment of Gastrointestinal Surgery, Peking University People’s HospitalDepartment of Radiology, Peking University People’s HospitalDepartment of General Surgery, Peking University People’s HospitalDepartment of Radiology, Peking University People’s HospitalAbstract Background To investigate the association between computed tomography (CT)-detected extramural venous invasion (EMVI)-related genes and immunotherapy resistance and immune escape in patients with gastric cancer (GC). Methods Thirteen patients with pathologically proven locally advanced GC who had undergone preoperative abdominal contrast-enhanced CT and radical resection surgery were included in this study. Transcriptome sequencing was multidetector performed on the cancerous tissue obtained during surgery, and EMVI-related genes (P value for association < 0.001) were selected. A single-sample gene set enrichment analysis algorithm was also used to divide all GC samples (n = 377) in The Cancer Genome Atlas (TCGA) database into high and low EMVI-immune related groups based on immune-related differential genes. Cluster analysis was used to classify EMVI-immune-related genotypes, and survival among patients was validated in TCGA and Gene Expression Omnibus (GEO) cohorts. The EMVI scores were calculated using principal component analysis (PCA), and GC samples were divided into high and low EMVI score groups. Microsatellite instability (MSI) status, tumor mutation burden (TMB), response rate to immune checkpoint inhibitors (ICIs), immune escape were compared between the high and low EMVI score groups. Hub gene of the model in pan-cancer analysis was also performed. Results There were 17 EMVI-immune-related genes used for cluster analysis. PCA identified 8 genes (PCH17, SEMA6B, GJA4, CD34, ACVRL1, SOX17, CXCL12, DYSF) that were used to calculate EMVI scores. High EMVI score groups had lower MSI, TMB and response rate of ICIs, status but higher immune escape status. Among the 8 genes used for EMVI scores, CXCL12 and SOX17 were at the core of the protein–protein interaction (PPI) network and had a higher priority in pan-cancer analysis. Immunohistochemical analysis showed that the expression of CXCL12 and SOX17 was significantly higher in CT-detected EMVI-positive samples than in EMVI-negative samples (P < 0.0001). Conclusion A CT-detected EMVI gene signature could be a potential negative biomarker for ICIs treatment, as the signature is negatively correlated with TMB, and MSI, resulting in poorer prognosis.https://doi.org/10.1186/s12967-022-03845-2RadiogenomicsExtramural venous invasionImmunotherapyGastric cancer |
| spellingShingle | Hao Yang Xinyi Gou Caizhen Feng Yinli Zhang Fan Chai Nan Hong Yingjiang Ye Yi Wang Bo Gao Jin Cheng Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer Journal of Translational Medicine Radiogenomics Extramural venous invasion Immunotherapy Gastric cancer |
| title | Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer |
| title_full | Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer |
| title_fullStr | Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer |
| title_full_unstemmed | Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer |
| title_short | Computed tomography-detected extramural venous invasion-related gene signature: a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer |
| title_sort | computed tomography detected extramural venous invasion related gene signature a potential negative biomarker of immune checkpoint inhibitor treatment in patients with gastric cancer |
| topic | Radiogenomics Extramural venous invasion Immunotherapy Gastric cancer |
| url | https://doi.org/10.1186/s12967-022-03845-2 |
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