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The Association Between C5 and Malignant Tumors

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C5 is the first complement molecule that forms the membrane attack complex (MAC). C5 is composed of ax and β chains connected by disulfide bonds. alpha chain is 115 KDa and the β chain is 75 KDa. There is no intra-chain thioester bond molecular weight of 190 KDa. The 74-75 arginine-leucine bond near the N-terminus is where C5 convertase acts. Under the action of C5 convertase, a small fragment C5a with a molecular weight of 11 KDa was cleaved into the liquid phase. C5a is the most potent mediator of complement lysis fragments with allergic toxins." Current studies indicate that high concentrations of C5a may reduce tumors by increasing Gr4 CD11b bone marrow cells in peripheral blood. Surface CD4, CD8T cells promote the formation of tumor blood vessels and inhibit apoptosis to promote tumor growth. Low concentrations of C5a can inhibit tumor growth by stimulating immune cells and blocking the cell cycle, or low concentrations of C5a can stimulate M1 phagocytes and NK cells to tumor. On the surface, both M1 phagocytes and NK cells have a certain anti-tumor effect and thus exhibit an indirect anti-tumor effect. Therefore, the tumor-related value of C5a has a certain concentration dependence. The concentration of C5a on the tumor surface may be the key to inhibition or promotion its performance. In addition, it has also been reported that the C5a receptor expressed on the surface of the tumor can significantly enhance the tumor's invasiveness, and the cytokines stimulated by C5a such as hepatocyte growth factor can also enhance the tumor's invasiveness.

At present, the research on the relationship between C5 and parenchymal organ fibrosis has been widely carried out. Boor et al.6 found that the mechanism of C5 involvement in parenchymal organ fibrosis may be related to the C5a receptor expressed on the cell surface, C5a stimulation-related cytokines and changes in parenchyma. Organ hemodynamics is related, on the other hand, there are studies that C5a has a biological relationship with liver regeneration. The three sites included in this study are all SNPs that are currently confirmed to be functional in the C5 gene. The rs17611 allele A was mostly severe cirrhosis patients and the rs2300929 allele C was mild cirrhosis patients. The C5 gene polymorphism has a clear relationship with the cirrhosis process. In another aspect, studies have indicated that the C5 serum concentration of carriers of rs17611 allele A and rs2300929 allele T is significantly higher than that of non-carriers. There is no relationship between C5 activity and C5 gene polymorphism, which suggests that there may be other factors affecting C5 activity. The gene polymorphism at rs25681 has also been shown to be associated with susceptibility to periodontitis. As in previous studies, this study also verified that there was a linkage disequilibrium among the three sites included, so that haplotype analysis was performed to obtain more genetic specificity than unit site analysis.

The results of this study show that the risk of HCC is significantly increased in those who carry the rs17611 allele G, rs25681 allele C and rs2300929 allele C, and the haplotype rs17611G-rs25681C-s2300929C can increase the risk of HCC. However, study showed that the C5 serum concentrations of carriers of rs17611 allele G and rs2300929 allele C were significantly lower than those of non-carriers, and low concentrations of C5a showed a certain anti-tumor growth effect, which is obvious different from this study. Different clinical phenotypes due to different diseases in different populations have been confirmed in a number of clinical genetic studies. In addition, Halangk et al. did not find C5 gene polymorphism and the degree of cirrhosis is related. This also shows that genetic polymorphism and clinical phenotype are not the same-there are many influencing factors in the corresponding relationship. How the C5 gene polymorphism affects its serum concentration is still unclear, and the tumor-related role of C5a is still unknown.

Since the liver is the main place for complement synthesis (80% to 90% of the complement components in plasma are synthesized in hepatocytes), hepatic stellate cells, Kupffer cells, and hepatic sinusoidal epithelial cells all express C5a receptors. These objective conditions clarify the role of the complement system in liver diseases, this study is the first to propose a correlation between C5 gene polymorphism and HCC susceptibility. In the future, screening and follow-up can be carried out in high-risk populations under the premise of improving the correlation between C5 gene polymorphism and C5 serum concentration and the pathogenesis of C5a serum concentration and HCC, to accurately assess the risk of HCC in individuals, so as to reach the early stage of preventing HCC.

Early detection and early treatment in the prevention and treatment of malignant tumors can significantly improve the patient's prognosis and quality of life. With the extensive use of genome-wide scanning technology, linkage analysis, family analysis and SNP as the third-generation genetic markers, we can gradually achieve early screening of malignant tumors or other diseases to obtain better clinical results. At present, C5a receptor blockers have been confirmed in experiments that can significantly slow down the progress of liver cirrhosis and reduce the content of collagen in liver cells. In addition, C5a-containing tumor vaccines can be used to inhibit tumor growth. Therefore, based on individualized early treatment considerations, if the C5 gene polymorphisms shown in the results of this study can be used as one of the basis, it may be more helpful for the development of related biological agents. The development of interrupted HCC helps to strengthen the prevention and treatment of HCC, further reduce the incidence of high-risk patients, reduce the mortality of HCC patients, and improve the prognosis of patients.


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