Objective To analyze the relation of tumor associated calcium signal transducer 2 (TACSTD2) gene with prognosis of patients with pancreatic cancer and its mechanism based on bioinformatics methods. Methods (1) The databases of GEPIA and TCGA were used to analyze expression of TACSTD2 gene in pancreatic cancerous tissues, and its relation with clinical pathological features of patients with pancreatic cancer. (2) The relation of TACSTD2 gene expression with survival status of cancer with pancreatic patients was analyzed by employing the databases of GEPIA and TISIDB, and COX regression model. (3) After obtaining co⁃expressed genes of TACSTD2 gene and differentially expressed genes between pancreatic cancer patients with different TACSTAD2 gene expressions by using the corresponding packages of R language software, the enrichment analyses were performed on genes as above. (4) The relation of TACSTD2 gene expression with immune microenvironment scores of patients with pancreatic cancer and level of immune cell infiltration in pancreatic cancerous tissues was analyzed by using the corresponding packages of R language software. (5) The correlation of TACSTD2 gene expression with immune checkpoint gene was analyzed. (6) The relations of TACSTD2 gene expression with immunophenoscore (IPS) of patients with pancreatic cancer, commonly mutated genes of pancreatic cancer, and sensitivity to targeted and chemotherapeutic drugs were evaluated and analyzed based on TCIA database, TIMER online database, R language software, respectively. (7) On the basis of STRING database and Cytoscape software, the protein⁃protein interaction network of TACSTD2 was established for screening proteins interacted closely with TACSTD2. Results (1) TACSTD2 gene was highly expressed in pancreatic cancerous tissues, and was related to pathological classification, clinical stage, and survival status of patients with pancreatic cancer. (2) TACSTD2 co⁃expressed genes were involved in biological processes of immune system process, etc. Differentially expressed genes were not only related to biological processes or cellular compositions such as immune system process, adaptive immune response, neuroactive ligand⁃receptor interaction, and immunoglobulin complex, but also closely related to signaling pathways of primary immunodeficiency, etc. (3) TACSTD2 gene expression positively correlated with infiltration levels of type M0 macrophages and Treg in pancreatic cancerous tissues, whereas negatively correlated with infiltration levels of CD8+ T lymphocytes, activated or resting CD4+ memory T lymphocytes (P<0.05). Pancreatic cancer patients with a high TACSTD2 expression obtained low scores of various immune microenvironment as compared with patients with a low expression (P<0.05), but there was no statistically significant difference in IPS between the two (P>0.05). (4) TACSTD2 gene expression positively correlated with expressions of immune checkpoint genes such as LGALS9, CD40, CD44, VTCN1, TNFRSF14, and CD276 (P<0.05). (5) The KRAS, TP53, and CDKN2A mutation groups yielded a higher expression of TACSTD2 as compared with the corresponding wild groups (P<0.05). Patients with a high TACSTD2 expression had higher sensitivity to trametinib and gefitinib than those with a low TACSTD2 expression (P<0.05). TACSTD2 protein might be closely related to EGFR, ERBB2, cyclin D1, and KRT7 proteins. Conclusion TACSTD2 may be regarded as potential biomarkers for evaluating prognosis of patients with pancreatic cancer, and it may be involved in the formation of immunosuppressive microenvironment of pancreatic cancer, and related to common genes mutations and sensitivity to drugs of pancreatic cancer, which is expected to be a target for diagnosing and treating pancreatic cancer.

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