BACKGROUND Mitophagy plays essential role in the development and progression of colorectal cancer(CRC). However, the effect of mitophagy-related genes in CRC remains largely unknown.AIM To develop a mitophagy-related ...BACKGROUND Mitophagy plays essential role in the development and progression of colorectal cancer(CRC). However, the effect of mitophagy-related genes in CRC remains largely unknown.AIM To develop a mitophagy-related gene signature to predict the survival, immune infiltration and chemotherapy response of CRC patients.METHODS Non-negative matrix factorization was used to cluster CRC patients from Gene Expression Omnibus database(GSE39582, GSE17536, and GSE37892) based on mitophagy-related gene expression. The CIBERSORT method was applied for the evaluation of the relative infiltration levels of immune cell types. The performance signature in predicting chemotherapeutic sensitivity was generated using data from the Genomics of Drug Sensitivity in Cancer database.RESULTS Three clusters with different clinicopathological features and prognosis were identified. Higher enrichment of activated B cells and CD4+ T cells were observed in cluster Ⅲ patients with the most favorable prognosis. Next, a risk model based on mitophagy-related genes was developed. Patients in training and validation sets were categorized into low-risk and highrisk subgroups. Low risk patients showed significantly better prognosis, higher enrichment of immune activating cells and greater response to chemotherapy(oxaliplatin, irinotecan, and 5-fluorouracil) compared to high-risk patients. Further experiments identified CXCL3 as novel regulator of cell proliferation and mitophagy.CONCLUSION We revealed the biological roles of mitophagy-related genes in the immune infiltration, and its ability to predict patients’ prognosis and response to chemotherapy in CRC. These interesting findings would provide new insight into the therapeutic management of CRC patients.展开更多
基金The study was reviewed and approved by the Fujian Cancer Ethics Committee(Approval No.K2023-030-01).
文摘BACKGROUND Mitophagy plays essential role in the development and progression of colorectal cancer(CRC). However, the effect of mitophagy-related genes in CRC remains largely unknown.AIM To develop a mitophagy-related gene signature to predict the survival, immune infiltration and chemotherapy response of CRC patients.METHODS Non-negative matrix factorization was used to cluster CRC patients from Gene Expression Omnibus database(GSE39582, GSE17536, and GSE37892) based on mitophagy-related gene expression. The CIBERSORT method was applied for the evaluation of the relative infiltration levels of immune cell types. The performance signature in predicting chemotherapeutic sensitivity was generated using data from the Genomics of Drug Sensitivity in Cancer database.RESULTS Three clusters with different clinicopathological features and prognosis were identified. Higher enrichment of activated B cells and CD4+ T cells were observed in cluster Ⅲ patients with the most favorable prognosis. Next, a risk model based on mitophagy-related genes was developed. Patients in training and validation sets were categorized into low-risk and highrisk subgroups. Low risk patients showed significantly better prognosis, higher enrichment of immune activating cells and greater response to chemotherapy(oxaliplatin, irinotecan, and 5-fluorouracil) compared to high-risk patients. Further experiments identified CXCL3 as novel regulator of cell proliferation and mitophagy.CONCLUSION We revealed the biological roles of mitophagy-related genes in the immune infiltration, and its ability to predict patients’ prognosis and response to chemotherapy in CRC. These interesting findings would provide new insight into the therapeutic management of CRC patients.
