Background and Objective: To explore the association between the expression, infiltration of immune cells, mechanism, and prognostic status of peptide N-acetylgalactosaminotransferase 5 (GALNT5) in pancreatic ductal cancer (PDAC) by Bioinformatics, and to verify the association between GALNT5 expression and clinical and pathological features with clinical data, aiming to find a new direction for immunotherapy and prognosis of PDAC clinical cases. Method: (1) Bioinformatics: The association of GALNT5 expression, prognosis, and immune microenvironment in PDAC tumor tissues was analyzed by using transcriptome sequencing data from the TCGA database, GTEx database, and GSE183795 microarray data from the GEO database. (2) Basic experiments: Pancreatic carcinoma microarray was adopted to further immunohistochemistry to verify the expression pattern of GALNT5 protein in PDAC tumor tissues and its association with clinical and pathological features. Results: The findings of bioinformatics demonstrated that GALNT5 was an up-regulated gene in ductal adenocarcinoma tissues (log2FC=2.609, P=0.026) compared with normal pancreatic tissues, and its expression in PDAC tumor tissues was substantially higher than that in non-tumor tissues (P<0.05), the OS (HR=1.6, P=0.038) and DFS (HR=1.8, P=0.012) of clinical cases with high expression of GALNT5 PDAC were lower than those of clinical cases with low expression. The expression of GALNT5 in pathological stage T3/4 was substantially higher than that in the T1/2 stage in PDAC clinical cases (P=0.0049). The prediction of the survival rate of GALNT5 in PDAC clinical cases is low, but the prolonged prognostic survival of PDAC clinical cases is better predicted. The analysis of infiltration of immune cells demonstrated that GALNT5 was negatively correlated with the infiltration levels of activated B cells, naïve CD8 T cells, and effector memory CD4 T cells (P<0.05), while it was positively correlated with NK cells (P<0.05). The findings of the GSEA enrichment analysis demonstrated that GALNT5 may be associated with the cell cycle and TGF-β signaling pathway in PDAC. (2) Immunohistochemistry results: 84 cases of Pancreatic carcinoma and 79 cases of para-tumor tissues were obtained by staining Pancreatic carcinoma tissue chip. The results demonstrated that 65 cases (77.38%) of GALNT5 were highly expressed in PDAC tumor tissues and 42 cases (53.16%) were highly expressed in para-tumor tissues, and the expression of GALNT5 in Pancreatic carcinoma tissues was statistically significant (X2=10.586, P=0.001). The expression of the GALNT5 gene was not statistically significant with the age, gender, tumor location, tumor stage, T stage, lymph node metastasis, distant metastasis, nerve invasion, differentiation degree, and tumor diameter in PDAC clinical cases (P>0.05). The Kaplan-Meier method was adopted to plot the survival probability curves between the GALNT5 high-expression group and the low-expression group, and the Log-rank test demonstrated that there was no significant difference in OS and DFS survival between the two groups (P=0.256, P=0.29> 0.05). Conclusion: GALNT5 is highly expressed in PDAC and is associated with poor prognosis in clinical cases. The mechanism of GALNT5 in PDAC affecting tumorigenesis and development may be associated with immune regulation, cell cycle, and TGF-β signaling pathway. GALNT5 may be a potential therapeutic target or biomarker for PDAC.
