Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics

Abstract Background Radiosensitivity of rectal cancer is related to the radiotherapy efficacy and prognosis of patients with rectal cancer, and the genes and molecular mechanisms related to radiosensitivity of rectal cancer have not been clarified. We explored the radiosensitivity related genes of r...

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Main Authors: Yi Liu, Yanguang Yang, Feng Ni, Guomei Tai, Cenming Yu, Xiaohui Jiang, Ding Wang
Format: Article
Language:English
Published: BMC 2023-11-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-023-04753-9
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author Yi Liu
Yanguang Yang
Feng Ni
Guomei Tai
Cenming Yu
Xiaohui Jiang
Ding Wang
author_facet Yi Liu
Yanguang Yang
Feng Ni
Guomei Tai
Cenming Yu
Xiaohui Jiang
Ding Wang
author_sort Yi Liu
collection DOAJ
description Abstract Background Radiosensitivity of rectal cancer is related to the radiotherapy efficacy and prognosis of patients with rectal cancer, and the genes and molecular mechanisms related to radiosensitivity of rectal cancer have not been clarified. We explored the radiosensitivity related genes of rectal cancer at a multi omics level. Methods mRNA expression data and rectum adenocarcinoma (READ) data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus Database (GEO) (GSE150082, GSE60331, GSE46862, GSE46862). Differentially expressed genes between radiotherapy sensitive group and radiotherapy insensitive group were screened. GO analysis and KEGG pathway analysis were performed for differentially expressed genes. Among the differentially expressed genes, five core genes associated with rectal cancer prognosis were selected using random survival forest analysis. For these five core genes, drug sensitivity analysis, immune cell infiltration analysis, TISIDB database immune gene correlation analysis, GSEA enrichment analysis, construction of Nomogram prediction model, transcriptional regulatory network analysis, and qRT-PCR validation was performed on human rectal adenocarcinoma tissue. Results We found that 600 up-regulated genes and 553 down-regulated genes were significantly different between radiotherapy sensitive group and radiotherapy insensitive group in rectal cancer. Five key genes, TOP2A, MATR3, APOL6, JOSD1, and HOXC6, were finally screened by random survival forest analysis. These five key genes were associated with different immune cell infiltration, immune-related genes, and chemosensitivity. A comprehensive transcriptional regulatory network was constructed based on these five core genes. qRT-PCR revealed that MATR3 expression was different in rectal cancer tissues and adjacent non-cancerous tissues, while APOL6, HOXC6, JOSD1, and TOP2A expression was not different. Conclusion Five radiosensitivity-related genes related to the prognosis of rectal cancer: TOP2A, MATR3, APOL6, JOSD1, HOXC6, are involved in multiple processes such as immune cell infiltration, immune-related genes, chemosensitivity, signaling pathways and transcriptional regulatory networks and may be potential biomarkers for radiotherapy of rectal cancer.
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spelling doaj.art-5a202181304c43059cfd9bc8a98efe552023-12-03T12:34:32ZengBMCJournal of Translational Medicine1479-58762023-11-0121112110.1186/s12967-023-04753-9Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omicsYi Liu0Yanguang Yang1Feng Ni2Guomei Tai3Cenming Yu4Xiaohui Jiang5Ding Wang6Department of Radiotherapy, Affiliated Tumor Hospital of Nantong University, Nantong Tumor HospitalDepartment of Radiotherapy, Affiliated Tumor Hospital of Nantong University, Nantong Tumor HospitalDepartment of Radiotherapy, Affiliated Tumor Hospital of Nantong University, Nantong Tumor HospitalDepartment of Radiotherapy, Affiliated Tumor Hospital of Nantong University, Nantong Tumor HospitalDepartment of Radiotherapy, Affiliated Tumor Hospital of Nantong University, Nantong Tumor HospitalDepartment of Gastrointestinal Surgery, Affiliated Tumor Hospital of Nantong University, Nantong Tumor HospitalDepartment of Gastrointestinal Surgery, Affiliated Tumor Hospital of Nantong University, Nantong Tumor HospitalAbstract Background Radiosensitivity of rectal cancer is related to the radiotherapy efficacy and prognosis of patients with rectal cancer, and the genes and molecular mechanisms related to radiosensitivity of rectal cancer have not been clarified. We explored the radiosensitivity related genes of rectal cancer at a multi omics level. Methods mRNA expression data and rectum adenocarcinoma (READ) data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus Database (GEO) (GSE150082, GSE60331, GSE46862, GSE46862). Differentially expressed genes between radiotherapy sensitive group and radiotherapy insensitive group were screened. GO analysis and KEGG pathway analysis were performed for differentially expressed genes. Among the differentially expressed genes, five core genes associated with rectal cancer prognosis were selected using random survival forest analysis. For these five core genes, drug sensitivity analysis, immune cell infiltration analysis, TISIDB database immune gene correlation analysis, GSEA enrichment analysis, construction of Nomogram prediction model, transcriptional regulatory network analysis, and qRT-PCR validation was performed on human rectal adenocarcinoma tissue. Results We found that 600 up-regulated genes and 553 down-regulated genes were significantly different between radiotherapy sensitive group and radiotherapy insensitive group in rectal cancer. Five key genes, TOP2A, MATR3, APOL6, JOSD1, and HOXC6, were finally screened by random survival forest analysis. These five key genes were associated with different immune cell infiltration, immune-related genes, and chemosensitivity. A comprehensive transcriptional regulatory network was constructed based on these five core genes. qRT-PCR revealed that MATR3 expression was different in rectal cancer tissues and adjacent non-cancerous tissues, while APOL6, HOXC6, JOSD1, and TOP2A expression was not different. Conclusion Five radiosensitivity-related genes related to the prognosis of rectal cancer: TOP2A, MATR3, APOL6, JOSD1, HOXC6, are involved in multiple processes such as immune cell infiltration, immune-related genes, chemosensitivity, signaling pathways and transcriptional regulatory networks and may be potential biomarkers for radiotherapy of rectal cancer.https://doi.org/10.1186/s12967-023-04753-9Rectal cancerDifferentially expressed genesRadiosensitivityMulti-omicsPrognosis
spellingShingle Yi Liu
Yanguang Yang
Feng Ni
Guomei Tai
Cenming Yu
Xiaohui Jiang
Ding Wang
Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics
Journal of Translational Medicine
Rectal cancer
Differentially expressed genes
Radiosensitivity
Multi-omics
Prognosis
title Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics
title_full Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics
title_fullStr Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics
title_full_unstemmed Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics
title_short Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics
title_sort research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi omics
topic Rectal cancer
Differentially expressed genes
Radiosensitivity
Multi-omics
Prognosis
url https://doi.org/10.1186/s12967-023-04753-9
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