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Houxi Xu,1,2,* Hongqun Zhang,1,3,* Songxian Sun,2,* Jingyuan Zhang,2 Jiege Huo,1,3 Chunxiang Zhou2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing, University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxiang Zhou, School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email chunxiangzhou@njucm.edu.cn Jiege Huo, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Email huojiege@jsatcm.comBackground: The CD1A gene, a key component of the human immune system and part of the CD1 family, plays a crucial role in presenting lipid antigens to T cells. Abnormal CD1A expression is associated with various immune-related diseases and tumors. However, the biological function of CD1A in COAD is unclear.Methods: Multiple databases were systematically employed to conduct an analysis of CD1A expression in pan-cancer and COAD, along with its clinical-pathological features. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of CD1A were performed using the ‘clusterProfiler’ package. The Protein-protein interaction (PPI) analysis of CD1A was used the STRING database. Additionally, TIMER and ssGSEA tools were used to explore the relationship between CD1A expression in COAD and immune cell infiltration. The study also investigated the association between CD1A expression and N6-methyladenosine (m6A) modification genes in the TCGA COAD cohort and constructed a CD1A-centric competing endogenous RNA (ceRNA) regulatory network.Results: CD1A displays varying expression levels in various tumors, including COAD, and is closely linked to clinical-pathological characteristics. GO analysis suggests that CD1A plays a role in important processes like antigen processing and presentation, leukocyte-mediated immunity, and lymphocyte-mediated immunity. KEGG analysis identifies CD1A’s involvement in key pathways such as the Chemokine signaling pathway and Cytokine-cytokine receptor interaction. PPI analysis highlights CD1A’s interactions with CD207, CD1C, CD1E, FOXP3, and ITGB2. ssGSEA analysis indicates a significant relationship between CD1A expression and the infiltration of various immune cells in COAD. Significant associations were found between CD1A and m6A modification genes in COAD. Furthermore, a CD1A-centered ceRNA regulatory network has been constructed.Conclusion: CD1A emerges as a potential biomarker for the diagnosis and treatment of COAD, showing a strong association with tumor immune infiltration, m6A modification, and the ceRNA network.Keywords: CD1A, COAD, immune infiltration, m6A, ceRNA

Houxi Xu,1,2,* Hongqun Zhang,1,3,* Songxian Sun,2 Jingyuan Zhang,2 Jiege Huo,1,3 Chunxiang Zhou2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing People’s Republic of China; 3The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunxiang Zhou, School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email chunxiangzhou@njucm.edu.cn Jiege Huo, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Email huojiege@jsatcm.comBackground: An increasing corpus of evidence has identified the involvement of N-acetyltransferase 1 (NAT1), a member of the NAT family, in the progression of various cancers. However, the specific function of NAT1 in colon cancer (COAD) remains elusive. This study aims to decip her the role of NAT1 in COAD and its associated mechanisms.Methods: The Tumor Immunity Evaluation Resource (TIMER), The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases were employed to assess the NAT1 expression level in COAD. The differential expression between COAD and normal colon tissue was further validated using quantitative real-time reverse-transcription PCR (RT-qPCR) and Western blot (WB) analyses. Additionally, survival analysis of NAT1 in COAD was carried out using the PrognoScan database and TCGA dataset. The functions of NAT1 were explored through gene set enrichment analysis (GSEA) and immuno-infiltration analysis.Results: There was a significant reduction in NAT1 expression in COAD samples compared to normal tissue. Notably, low NAT1 expression in COAD correlated significantly with various clinical parameters such as tumor stage (T stage, N stage, M stage, pathologic stage), primary therapy outcome, carcinoembryonic antigen (CEA) level, and lymphatic invasion. The downregulation of NAT1 was also strongly linked with poor outcomes in overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS). Cox regression analysis highlighted NAT1 as an independent prognostic indicator for overall survival in COAD patients. GSEA results revealed NAT1’s involvement in multiple pathways, including the neuroactive ligand-receptor interaction, olfactory transduction, olfactory signaling, extracellular matrix receptor interaction, calcium signaling, and focal adhesion pathways. Furthermore, NAT1 expression was found to significantly correlate with infiltration levels of various immune cells.Conclusion: The findings reveal NAT1’s potential as a valuable prognostic biomarker for COAD. Moreover, its associated mechanisms offer insights that might pave the way for therapeutic interventions for COAD patients.Keywords: NAT1, COAD, prognosis, immune infiltration, RT-qPCR, western blot

Purpose: This study aims to systematically analyze multi-omics data to explore new prognosis biomarkers in colon adenocarcinoma (COAD)., Materials and Methods: Multi-omics data of COAD and clinical information were obtained from The Cancer Genome Atlas (TCGA). Univariate Cox analysis was used to select genes which significantly related to the overall survival. GISTIC 2.0 software was used to identify significant amplification or deletion. Mutsig 2.0 software was used to identify significant mutation genes. The 9-gene signature was screened by random forest algorithm and Cox regression analysis. GSE17538 dataset was used as an external dataset to verify the predictive ability of 9-gene signature. qPCR was used to detect the expression of 9 genes in clinical specimens., Results: A total of 71 candidate genes are obtained by integrating genomic variation, mutation and prognostic data. Then, 9-gene signature was established, which includes HOXD12, RNF25, CBLN3, DOCK3, DNAJB13, PYGO2, CTNNA1, PTPRK, and NAT1. The 9-gene signature is an independent prognostic risk factor for COAD patients. In addition, the signature shows good predicting performance and clinical practicality in training set, testing set and external verification set. The results of qPCR based on clinical samples showed that the expression of HOXD12, RNF25, CBLN3, DOCK3, DNAJB13, and PYGO2 was increased in colon cancer tissues and the expression of CTNNA1, PTPRK, NAT1 was decreased in colon cancer tissues., Conclusion: In this study, 9-gene signature is constructed as a new prognostic marker to predict the survival of COAD patients., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Lu et al.)