The Mechanism Of Tumor-associated Macrophages Promoting The Progression Of Colorectal Cancer By Regulating C1QBP

BackgroundColorectal cancer(CRC)is the most common malignancy of the digestive tract.In 2020,the incidence of colorectal cancer ranks third in the world,and the mortality rate ranks second in the world.Although targeted therapy and immunotherapy have improved the prognosis of CRC,there are still a large number of patients who can’t benefit from it.Therefore,it’s an urgent problem to find new therapeutic target to improve the prognosis of CRC patients.Tumor-associated macrophage(TAM)are the largest number of immune cells in tumor microenvironment(TME),which is related to the poor prognosis of many kinds of malignant tumors,but it is not clear in CRC.Metabolic reprogramming has been recognized as a feature of cancer.The complement C1q binding protein(C1QBP)is an important substance that affects the mitochondrial respiration of tumor cells and is closely related to tumor metabolism.Therefore,understanding the role of TAM and C1QBP in CRC is helpful to improve the prognosis of CRC patients.ObjectivesTo explore the effect of C1QBP and CD163 on the prognosis of CRC patients and the effect of TAM in CRC on C1QBP.MethodsThe expression of C1QBP and CD163 in CRC cancerous tissues and para-cancerous tissues was detected by qPCR and IHC,and the relationship between C1QBP and CD163 and clinicopathological parameters was analyzed byX~2test.Using Kaplan-Meier Survival Analysis to explore the relationship between C1QBP,CD163 and Overall Survival(OS)time of CRC patients with.COX univariate analysis was used to study the factors affecting the prognosis of CRC patients,Cox multivariate analysis was identified independent predictors of CRC prognosis.The effects of C1QBP on the proliferation,migration and 5-FU sensitivity of HCT116 cells were studied by colony forming assay,cell scratch assay and MTT cytotoxicity assay.Results1.IHC and qPCR results showed that the expression of C1QBP and CD163 in CRC tissues was higher than that in adjacent tissues.2.The expression of C1QBP was significantly correlated with histological differentiation(P<0.05),vascular invasion(P<0.05)and TNM stage(P<0.05).The expression of CD163 was significantly correlated with histological differentiation(P<0.05),lymph node metastasis(P<0.05),T grade(P<0.05),TNM stage(P<0.05).3.Kaplan-Meier survival analysis found that patients with high expression of C1QBP had significantly shorter OS after surgery compared with patients with low expression of C1QBP(P<0.0001),compared with patients with low expression of CD163,patients with high expression of CD163 had significantly shorter OS(P=0.0001).4.COX univariate analysis showed that BMI index,lymph node metastasis,TNM stage,C1QBP expression and CD163 expression were significantly correlated with postoperative survival of CRC patients.When these factors were included in COX multivariate analysis,high expression of C1QBP was an independent risk factor for prognosis.5.The overexpression of C1QBP promoted the proliferation and migration of HCT116 cells and decreased the sensitivity to 5-FU,while interfering with the expression of C1QBP inhibited the proliferation and migration of HCT116 cells and improve the sensitivity to 5-FU.6.IL-10 in the culture supernatant of TAM cells promotes the expression of C1QBP in HCT116 cells.Conclusions1.The expression of C1QBP and CD163 in colorectal cancer tissues was higher than that in adjacent tissues.The expression of C1QBP was significantly correlated with histological differentiation,vascular invasion and TNM stage,and the expression of CD163 was significantly correlated with histological differentiation,lymph node metastasis,T grade and TNM stage.2.The high expression of C1QBP and CD163 are both predictors of poor prognosis in CRC patients,and the high expression of C1QBP is an independent risk factor affecting the prognosis of CRC.3.Overexpression of C1QBP promotes the proliferation and migration of CRC cell,and decreased the sensitivity to 5-FU.Interference with C1QBP inhibited the proliferation and migration of CRC cells,and increased the sensitivity to 5-FU.4.IL-10 in the supernatants of promoted the expression of C1QBP in HCT116 cells.