An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer
Background and purposeAccumulating evidence indicates that neoadjuvant chemoradiotherapy(nCRT) success has an immune-associated constituent in locally advanced rectal cancer (LARC). The immune-associated configuration of the tumor microenvironment associated with responses to treatment was explored...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.993726/full |
| _version_ | 1828385221972590592 |
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| author | Zhengfa Xue Zhengfa Xue Shuxin Yang Yun Luo Ming He Huimin Qiao Wei Peng Suxin Tong Guini Hong You Guo |
| author_facet | Zhengfa Xue Zhengfa Xue Shuxin Yang Yun Luo Ming He Huimin Qiao Wei Peng Suxin Tong Guini Hong You Guo |
| author_sort | Zhengfa Xue |
| collection | DOAJ |
| description | Background and purposeAccumulating evidence indicates that neoadjuvant chemoradiotherapy(nCRT) success has an immune-associated constituent in locally advanced rectal cancer (LARC). The immune-associated configuration of the tumor microenvironment associated with responses to treatment was explored in LARC in this study.Material and methodsA novel analytic framework was developed based on within-sample relative expression orderings for identifying tumor immune-associated gene pairs and identified an immuno-score signature from bulk transcriptome profiling analysis of 200 LARC patients. And sequencing and microarray analysis of gene expression was conducted to investigate the association between the signature and response to nCRT, immunotherapy, and cell function of CD4 and CD8. The results were validated using 111 pretreated samples from publicly available datasets in multiple aspects and survival analyses.ResultsThe immuno-score signature of 18 immune-related gene pairs (referred to as IPS) was validated on bulk microarray and RNA-Seq data. According to the model’s immune score, LARC patients were divided into high- and low-score groups. The patients with high-score were greater sensitivity to nCRT and immunotherapy, gaining a significantly improved prognosis. In addition, the immune-score gene pair signature was associated with type I anti-tumor T cell responses, positive regulators of T cell functions, and chromosomal instability while reflecting differences between CD8+ T cell subtypes.ConclusionThe immuno-score signature underlines a key role of tumor immune components in nCRT response, and predicts the prognosis of LARC patients as well. |
| first_indexed | 2024-12-10T05:16:50Z |
| format | Article |
| id | doaj.art-3c186caf71634945bd30cade2aad840a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T05:16:50Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3c186caf71634945bd30cade2aad840a2022-12-22T02:00:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.993726993726An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancerZhengfa Xue0Zhengfa Xue1Shuxin Yang2Yun Luo3Ming He4Huimin Qiao5Wei Peng6Suxin Tong7Guini Hong8You Guo9Medical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaDepartment of Computer Science and Technology, School of Electronic and Information Engineering, Xi’an Jiao Tong University, Xi’an, ChinaSchool of Information Engineering, Jiangxi University of Science and Technology, Ganzhou, ChinaMedical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaMedical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaMedical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaMedical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaSchool of Information Engineering, Jiangxi University of Science and Technology, Ganzhou, ChinaSchool of Medical Information Engineering, Gannan Medical University, Ganzhou, ChinaMedical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaBackground and purposeAccumulating evidence indicates that neoadjuvant chemoradiotherapy(nCRT) success has an immune-associated constituent in locally advanced rectal cancer (LARC). The immune-associated configuration of the tumor microenvironment associated with responses to treatment was explored in LARC in this study.Material and methodsA novel analytic framework was developed based on within-sample relative expression orderings for identifying tumor immune-associated gene pairs and identified an immuno-score signature from bulk transcriptome profiling analysis of 200 LARC patients. And sequencing and microarray analysis of gene expression was conducted to investigate the association between the signature and response to nCRT, immunotherapy, and cell function of CD4 and CD8. The results were validated using 111 pretreated samples from publicly available datasets in multiple aspects and survival analyses.ResultsThe immuno-score signature of 18 immune-related gene pairs (referred to as IPS) was validated on bulk microarray and RNA-Seq data. According to the model’s immune score, LARC patients were divided into high- and low-score groups. The patients with high-score were greater sensitivity to nCRT and immunotherapy, gaining a significantly improved prognosis. In addition, the immune-score gene pair signature was associated with type I anti-tumor T cell responses, positive regulators of T cell functions, and chromosomal instability while reflecting differences between CD8+ T cell subtypes.ConclusionThe immuno-score signature underlines a key role of tumor immune components in nCRT response, and predicts the prognosis of LARC patients as well.https://www.frontiersin.org/articles/10.3389/fonc.2022.993726/fullimmuno-score signaturelocally advanced rectal cancerneoadjuvant chemoradiotherapyimmune gene pairsprognostic prediction |
| spellingShingle | Zhengfa Xue Zhengfa Xue Shuxin Yang Yun Luo Ming He Huimin Qiao Wei Peng Suxin Tong Guini Hong You Guo An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer Frontiers in Oncology immuno-score signature locally advanced rectal cancer neoadjuvant chemoradiotherapy immune gene pairs prognostic prediction |
| title | An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer |
| title_full | An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer |
| title_fullStr | An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer |
| title_full_unstemmed | An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer |
| title_short | An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer |
| title_sort | immuno score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer |
| topic | immuno-score signature locally advanced rectal cancer neoadjuvant chemoradiotherapy immune gene pairs prognostic prediction |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.993726/full |
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