Peroxisomes are pivotal metabolic organelles that exist in almost all eukaryote cells. A reduction in numbers and enzymatic activities of peroxisomes was found in colon adenocarcinomas. However, the role of peroxisomes or the peroxisome pathway in colorectal cancer (CRC) is not defined. | Yin et al. BMC Cancer 2022 22 44 https s12885-021-09085-9 RESEARCH Open Access Identification of an at-risk subpopulation with high immune infiltration based on the peroxisome pathway and TIM3 in colorectal cancer Jinwen Yin1 2 Hao Wang1 2 Yuntian Hong1 3 Anli Ren1 2 Haizhou Wang1 2 Lan Liu1 2 and Qiu Zhao1 2 Abstract Background Peroxisomes are pivotal metabolic organelles that exist in almost all eukaryote cells. A reduction in numbers and enzymatic activities of peroxisomes was found in colon adenocarcinomas. However the role of peroxi- somes or the peroxisome pathway in colorectal cancer CRC is not defined. Methods In the current study a peroxisome score was calculated to indicate the activity of the peroxisome pathway using gene set variant analysis based on transcriptomic datasets. CIBERSORTx was chosen to infer enriched immune cells for tumors among subgroups. The SubMap algorithm was applied to predict its sensitivity to immunotherapy. Results The patients with a relatively low peroxisome score and high level of T-cell immunoglobulin and mucin domain 3 TIM-3 presented the worse overall survival than others. Moreover low peroxisome scores were associ- ated with high infiltration of lymphocytes and poor prognosis in those CRC patients. Thus a P ERLowTIM3High CRC risk subpopulation was identified and characterized by high immune infiltration. The results also showed that CD8 T cells and macrophages highly infiltrated tumors of the PERLowTIM3High group regardless of consortium molecular subtype and microsatellite instability status. This subgroup had the highest tumor mutational burden and overex- pression of immune checkpoint genes. Further the PERLowTIM3High group showed a higher probability of responding to programmed cell death protein-1-based immunotherapy. In addition genes involved in peroxisomal metabolic processes in CRC were also investigated since peroxisome is a rather pleiotropic and highly metabolic organelle in cell. The results .
