Background: Hepatocellular carcinoma (HCC) is an inflammation-associated tumor involved in immune tolerance and evasion in the immune microenvironment. Immunotherapy can enhance the body's immune response, break immune tolerance, and then recognize and kill tumor cells. The polarization homeostasis of M1 and M2 macrophages in tumor microenvironment (TME) is involved in the occurrence and development of tumor, which is a hot topic in tumor research. Programmed cell death ligand 1 (PD-L1) plays an important role in the polarity of TAM and affects the prognosis of HCC patients as a target of immunotherapy. Therefore, we further explored the application value of PD-L1, M1 macrophages (CD86) and M2 macrophages (CD206) in the prognosis assessment of HCC, their correlation with immune cell infiltration in HCC tissues, and their bioenrichment function. Methods: The gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) database were used to analyze the expression of PD-L1, CD86 and CD206 in different tumor tissues. The Tumor Immune Estimation Resource (TIMER) was used to analyze the correlation between the expression of PD-L1, CD86 and CD206 and the infiltration of immune cells. The tissue specimens and clinicopathological data of hepatocellular carcinoma patients who underwent surgical treatment in our hospital were collected. Immunohistochemistry was used to verify the expression of PD-L1, CD86 and CD206, and analyze the relationship with clinicopathological features and prognosis of patients. Nomogram was constructed to predict the overall survival (OS) of patients at 3 and 5 years. Finally, STRING database was used to analyze the protein-protein interaction network information, and GO analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis were performed to study the biological functions of PD-L1, CD86 and CD206. Result:Bioinformatics analysis found that PD-L1, CD86 and CD206 were all under-expressed in a variety of tumor tissues including liver cancer, while our immunohistochemical analysis found the opposite result, and PD-L1, CD86 and CD206 were all over-expressed in liver cancer tissues. The expressions of PD-L1, CD86 and CD206 were positively correlated with the level of immune cell infiltration in HCC tissues; The expression of PD-L1 is positively correlated with the degree of tumor differentiation; The expression level of CD206 was positively correlated with gender and whether patients had hepatitis before operation. The prognosis of patients with low expression of PD-L1 or CD86 is poor. AJCC stage, preoperative hepatitis, and the expression level of CD206 in adjacent tissues are independent risk factors affecting the survival of patients after radical hepatectomy. KEGG pathway enrichment analysis showed that PD-L1 was significantly enriched in T cell aggregation and lymphocyte aggregation, and may be involved in the formation of T cell antigen receptor CD3 complex and cell membrane. CD86 was significantly enriched in positive regulation of cell adhesion, regulation of mononuclear cell proliferation, regulation of leukocyte proliferation and transduction of T cell receptor signaling pathway. CD206 was significantly enriched in type 2 immune response, cellular response to LPS, cellular response to LPS, and involvement in cellular response to LPS. Conclusion: In conclusion, these results suggest that PD-L1, CD86 and CD206 may not only be involved in the occurrence and development of HCC, but also in immune regulation. Therefore, PD-L1, CD86 and CD206 can be used as potential biomarkers and new therapeutic targets for HCC prognosis assessment.

Background Hepatocellular carcinoma (HCC) is an inflammation-associated tumor involved in immune tolerance and evasion in the immune microenvironment. Immunotherapy can enhance the immune response of the body, break immune tolerance, and then recognize and kill tumor cells. The polarization homeostasis of M1 and M2 macrophages in tumor microenvironment (TME) is involved in the occurrence and development of tumors and has been considered a hot topic in tumor research. Programmed cell death ligand 1 (PD-L1) plays an important role in the polarity of TAM and affects the prognosis of HCC patients as a target of immunotherapy. To this end, efforts were hereby made to further explore the application value of PD-L1, M1 macrophages (CD86), and M2 macrophages (CD206) in the prognosis assessment of HCC, their correlation with immune cell infiltration in HCC tissues, and their bioenrichment function. Methods The gene expression omnibus (GEO) and the Cancer Genome Atlas (TCGA) database were used to analyze the expression of PD-L1, CD86, and CD206 in different tumor tissues. The correlation between the expression of PD-L1, CD86, and CD206 and the infiltration of immune cells was analyzed using the Tumor Immune Estimation Resource (TIMER). The tissue specimens and clinicopathological data of hepatocellular carcinoma patients having undergone surgical treatment in our hospital were collected. Immunohistochemistry was used to verify the expression of PD-L1, CD86, and CD206, and analyze the relationship with clinicopathological features and prognosis of patients. Besides, nomogram was constructed to predict the overall survival (OS) of patients at 3 and 5 years. Finally, the protein–protein interaction network information was analyzed using STRING database, and GO analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis were performed to study the biological functions of PD-L1, CD86, and CD206. Result Bioinformatics analysis found that PD-L1, CD86, and CD206 were underexpressed in various tumor tissues including liver cancer, while the present immunohistochemical detection found that PD-L1, CD86, and CD206 were overexpressed in liver cancer tissues. Expressions of PD-L1, CD86, and CD206 were positively correlated with the infiltration level of immune cells in liver cancer, while the expression of PD-L1 was positively correlated with the degree of tumor differentiation. Meanwhile, the expression level of CD206 was positively correlated with gender and preoperative hepatitis, and patients with high expression of PD-L1 or low expression of CD86 had poor prognosis. AJCC stage, preoperative hepatitis, and the expression levels of PD-L1 and CD86 in cancer tissues were independent risk factors affecting survival of patients after radical hepatoma surgery. KEGG pathway enrichment analysis showed that PD-L1 was significantly enriched in T cell aggregation and lymphocyte aggregation, and might be involved in the formation of T cell antigen receptor CD3 complex and cell membrane. Besides, CD86 was significantly enriched in positive regulation of cell adhesion, regulation of mononuclear cell proliferation, regulation of leukocyte proliferation, and transduction of T cell receptor signaling pathway, while CD206 was significantly enriched in type 2 immune response, cellular response to LPS, cellular response to LPS, and involvement in cellular response to LPS. Conclusion In conclusion, these results suggest that PD-L1, CD86, and CD206 may be involved not only in the occurrence and development of HCC, but also in immune regulation, indicating the potential role of PD-L1 and CD86 as potential biomarkers and new therapeutic targets for prognosis assessment of liver cancer.

Background: Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been found to act as miRNA sponges that competitively inhibit the binding of miRNA to target mRNA. However, studies on circRNA in pancreatic ductal adenocarcinoma are still lacking and need to be further explored. Methods: The expression level of SOX4 in pancreatic cancer cells and tissues was detected by qRT-PCR and immunohistochemistry, and the correlation between the expression level of SOX4 in pancreatic cancer tissues and clinicopathological features was analyzed by Pearson Chi-square test. Kaplan-meier method was used to analyze the survival curve of pancreatic cancer patients. The circRNA regulating SOX4 was predicted by bioinformatics and verified in pancreatic cancer cells and tissues. The miRNA and target genes were predicted by bioinformatics, and the circRNA-miRNA-mRNA regulatory network was constructed. Then, the expression of SFRP2 in pancreatic cancer cells and tissues was detected by qRT-PCR and immunohistochemistry, and the correlation between clinicopathological features and prognosis was analyzed. Finally, the biological function of SFRP2 was analyzed by bioinformatics to construct a prognostic model for pancreatic cancer. Result: The expression level of SOX4 was significantly up-regulated in various tumor tissues including pancreatic ductal adenocarcinoma. Further analysis showed that up-regulated SOX4 expression was correlated with tumor size and T stage of patients and resulted in poor prognosis of patients. Bioinformatics analysis revealed that SOX4 was a key protein in the Wnt/β-catenin pathway. QRT-PCR was used to detect tissue samples and cells of 9 pancreatic cancer patients, and the expression of 4 circRNA was down-regulated, among which hsa_circ_0131457 was the most significant. A total of 10 miRNA were selected for the prediction of miRNA that bind to hsa_circ_0131457, and the optimal matching value was miR-636. The mRNA targeted to miR-636 was predicted, SFRP2 with the most obvious differential expression was screened out, and the hsa_circ_0131457-miR-636-SFRP2 network regulation map was constructed. Analysis and verification of the target gene SFRP2 showed that the expression of SFRP2 was significantly down-regulated in pancreatic cancer tissues and cells, which was related to preoperative direct bilirubin, tumor size, T stage and tumor differentiation degree. In addition, downregulation of SFRP2 expression in cancer tissues predicted poor prognostic survival in pancreatic cancer patients. Functional analysis of SFRP2 revealed that SFRP2 is a key protein in the Wnt/β-catenin pathway and may be involved in epithelial-mesenchymal transition (EMT). Conclusion: hsa_circ_0131457 and target gene SFRP2 were found to be low expressed in pancreatic cancer, and SFRP2 had an inhibitory effect on the progression of pancreatic cancer. Therefore, the potential regulatory mechanism of hsa_circ_0131457/miR-636/SFRP2 inhibiting the invasion and metastasis of pancreatic cancer was inferred.