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Research on radiotherapy related genes and prognostic target identification of rectal cancer based on multi-omics
Yi Liu1, Yanguang Yang1, Feng Ni1
1Department of Radiotherapy, Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu, China.
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.
Insights
Researchers identified five key genes (TOP2A, MATR3, APOL6, JOSD1, HOXC6) linked to rectal cancer radiosensitivity and patient prognosis. These genes may serve as potential biomarkers for improving radiotherapy efficacy in rectal cancer treatment.
Area of Science:
- Oncology
- Genetics
- Radiotherapy
Background:
- Rectal cancer radiosensitivity is crucial for treatment efficacy and patient outcomes.
- The specific genes and molecular mechanisms influencing rectal cancer radiosensitivity remain largely unclear.
- This study aimed to identify radiosensitivity-related genes in rectal cancer using a multi-omics approach.
Purpose of the Study:
- To explore genes associated with rectal cancer radiosensitivity.
- To identify potential molecular biomarkers for predicting radiotherapy response in rectal cancer patients.
- To investigate the role of these genes in immune infiltration, drug sensitivity, and prognosis.
Main Methods:
- Utilized mRNA expression data from TCGA and GEO databases for rectum adenocarcinoma (READ).
- Screened differentially expressed genes between radiosensitive and radioinsensitive groups, followed by GO and KEGG pathway analyses.
- Employed random survival forest analysis to identify five core prognostic genes, followed by drug sensitivity, immune cell infiltration, and transcriptional regulatory network analyses, and qRT-PCR validation.
Main Results:
- Identified 600 up-regulated and 553 down-regulated genes between radiosensitive and radioinsensitive rectal cancer groups.
- Five key genes (TOP2A, MATR3, APOL6, JOSD1, HOXC6) were selected as core genes associated with rectal cancer prognosis.
- These genes demonstrated associations with immune cell infiltration, immune-related genes, and chemosensitivity; MATR3 showed differential expression in tumor tissues.
Conclusions:
- Discovered five radiosensitivity-related genes (TOP2A, MATR3, APOL6, JOSD1, HOXC6) impacting rectal cancer prognosis.
- These genes are implicated in immune infiltration, immune-related genes, chemosensitivity, and transcriptional networks.
- These findings suggest potential utility of these genes as biomarkers for rectal cancer radiotherapy.
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