Identification of NUDT6 and LINGO1 as key genes for predicting response to neoadjuvant chemoradiotherapy in rectal cancer patients

Background Rectal cancer is a highly prevalent cancer worldwide and a common cause of cancer death. Neoadjuvant chemoradiotherapy (nCRT) is the first choice for advanced rectal cancer. In this study, we used bioinformatics approaches to explore key genes affected by nCRT in rectal cancer. Methods A total of 26 samples of rectal cancer patients were collected and divided into the Treatment group (14 patients who received nCRT) and the Control group (12 patients who did not receive nCRT). Key genes were selected by high-throughput sequencing, differential expression analysis, machine learning algorithms, receiver operating characteristic (ROC) curves, and gene expression analysis. Gene Set Enrichment Analysis (GSEA) was used to trace the enrichment pathways of these key genes. Additionally, the relationship between immune cells and these key genes was explored. A nomogram and molecular regulatory network were constructed based on the selected key genes. Results The quality of sequencing data was high for all samples. Overall, 35 differentially expressed genes (DEGs) were discovered. Among them, NUDT6 and LINGO1 had excellent predictive values (both with area under the curve (AUC) > 0.8) and were identified as key genes. A nomogram with good diagnostic performance was constructed. NUDT6 was significantly enriched in the ribosome and oxidative phosphorylation pathways, and was significantly positively correlated with Megakaryocyte-Erythroid Progenitor (MEP) and T helper cell 1 (Th1 cells), and significantly negatively correlated with Myocyte cells. LINGO1 was significantly enriched in the proteasome pathway and significantly positively correlated with Erythrocytes. Additionally, drug prediction analyses indicated that valproic acid was most highly associated with NUDT6, while bisphenol A is most closely linked to LINGO1. Conclusions In this study, the NUDT6 and LINGO1 genes were identified as key genes related to nCRT in rectal cancer. These genes might significantly influence the sensitivity of rectal cancer to nCRT, and the findings could provide valuable insights for developing personalized treatment strategies.