Identification of NUDT6 and LINGO1 as candidate genes for nCRT-associated signatures to neoadjuvant chemoradiotherapy in rectal cancer patients

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 candidate genes affected by nCRT in rectal cancer. 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). candidate 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 candidate genes. Additionally, the relationship between immune cells and these candidate genes was explored. A nomogram and molecular regulatory network were constructed based on the selected candidate genes. The quality of sequencing data was high for all samples. Overall, 35 differentially expressed genes (DEGs) were discovered. Among them, NUDT6 and LINGO1 were identified as candidate genes with high discriminative ability (both with area under the curve (AUC) > 0.8). A nomogram with satisfactory exploratory 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. In this study, NUDT6 and LINGO1 were identified as potential candidate genes significantly associated with the Treatment group (patients who received nCRT) compared to the Control group (patients who did not). These findings may offer exploratory insights into the molecular correlates of nCRT treatment in rectal cancer. Moreover, as this study relies on a single-center convenience sample, these findings require further validation in multi-center prospective cohorts.