Expression Of HIPPO Pathway In Colorectal Cancer And Its Biological Significance

Objective:To explore the expression changes of key factors of the Hippo signal pathway in colorectal cancer and analyze the correlation between their expression changes.To further clarify the relationship between its expression and clinicopathological characteristics,and provide laboratory data and a theoretical basis for the occurrence and development of colorectal cancer.Methods:Retrospectively collected 100 samples of colorectal cancer patients who underwent radical and palliative surgery in the People’s Hospital of Inner Mongolia Autonomous Region from March 2020 to March 2021.Relevant clinical and pathological data were obtained through the patient’s electronic medical record.The expression of NF2,MST1/2,p-MST1/2,LAST1,p-LAST1/2,YAP1,and p-YAP in colorectal cancer and normal tissues adjacent to cancer were detected by immunohistochemical staining.The relationship and correlation between the expression of key factors of the Hippo signal pathway and various clinicopathologic features of colorectal cancer were analyzed by statistical software;The 100 patients with colorectal cancer were followed up to analyze the correlation and risk factors between the expression of key factors of Hippo signal pathway and the prognosis of patients.Results:The expression of NF2 in colorectal cancer tissues(positive rate 47%)was significantly lower than that in normal tissues adjacent to cancer(positive rate 77%),(χ~2=19.100,P<0.0015).The expression of MST1/2 in colorectal cancer tissues(positive rate 47%)was significantly lower than that in normal tissues adjacent to cancer(positive rate 73%),(χ~2=14.083,P<0.001).The expression of p-MST1/2 in colorectal cancer tissue(positive rate 34%)was significantly lower than that in normal tissues adjacent to cancer(positive rate of 70%),(χ~2=25.962,P<0.001).The expression of LATS1 in colorectal cancer tissues(positive rate 47%)was significantly lower than that in normal tissues adjacent to cancer(positive rate 96%),(χ~2=58.913,P<0.001).The expression of p-LATS1/2 in colorectal cancer tissues(positive rate 40%)was significantly lower than that in normal tissues adjacent to cancer(positive rate89%),(χ~2=22.134,P<0.001);The expression of YAP1 in colorectal cancer tissues(positive rate 69%)was significantly higher than that in normal tissues adjacent to cancer(positive rate 26%),(χ~2=37.073,P<0.001).The expression of p-YAP in colorectal cancer tissues(positive rate 48%)was significantly lower than that in normal tissues adjacent to cancer(positive rate 65%),(χ~2=5.529,P=0.019).The expression of NF2 was related to the degree of tumor differentiation,TNM stage,tumor size,lymph node metastasis,distant metastasis,and vascular invasion,and the difference was statistically significant(P<0.05),but had nothing to do with gender,age,BMI,depth of invasion and other factors;The expression of MST1/2 was related to BMI,tumor stage,tumor size,and lymph node metastasis,and the difference was statistically significant(P<0.05),but not related to age,gender,degree of differentiation,depth of invasion,and vascular invasion.The expression of LATS1 is related to tumor stage,tumor size,lymph node metastasis,distant metastasis,invasion depth,and the difference is statistically significant(P<0.05),and has nothing to do with gender,age,BMI,and other factors;the expression of YAP1 is related to age,tumor differentiation degree,tumor Stage,depth of invasion,and distant metastasis were related,and the difference was statistically significant(P<0.05),but not related to factors such as gender,BMI,tumor size,and vascular invasion.In colorectal cancer,the expression of NF2 was significantly negatively correlated with the expression of YAP1(r=-0.208,P=0.038),and significantly positively correlated with the expression of p-YAP(r=0.251,P=0.012).It was positively correlated with LATS1 and MST1/2,but the result was not statistically significant(P>0.05).The expression of MST1/2was positively correlated with the expression of LATS1,p-LATS1/2,and p-YAP respectively(r=0.237,P=0.017;r=0.506,P<0.001;r=0.383,P<0.001).The expression of p-MST1/2 was significantly positively correlated with the expression of p-LATS1/2and p-YAP respectively(r=0.312,P=0.002;r=0.297,P=0.003).The expression of LATS1 and p-LATS1/2 was positively correlated with the expression of p-YAP respectively(r=0.338,P=0.001;r=0.317,P=0.001).Kaplan-Meier survival analysis showed that in colorectal cancer,the NF2 positive group had a higher survival rate than the NF2 negative group,and the survival curves of the two groups were statistically different(χ~2=9.217,P=0.002);The survival rate of p-MST1/2 negative group is higher than that of p-MST1/2 positive group,and the survival curve of the two groups have a statistical difference(χ~2=5.327,P=0.021);The expression of MST1/2,LATS1,p-LATS1/2,YAP1,and p-YAP had no significant effect on the survival rate of patients(P>0.05).Using multivariate Cox proportional risk regression analysis,the HR of CEA is greater than 1,and the HR of NF2 and p-MST1/2 is less than 1.The results showed that NF2 and p-MST1/2 were protective factors affecting the prognosis of patients(P=0.003;P=0.016).CEA was a risk factor affecting the prognosis of patients(P=0.037).Conclusion:1.The high expression of NF2,MST1/2,p-MST1/2,LATS1,p-LATS1/2,and p-YAP inhibits colorectal cancer,and the high expression of YAP1 promotes the occurrence and development of colorectal cancer.2.The expression of NF2,MST1/2,LATS1,and YAP1 is closely related to the TNM stage and lymph node metastasis of colorectal cancer,indicating that the Hippo signaling pathway may play an important role in the occurrence,development,and metastasis of colorectal cancer.3.In colorectal cancer tissues,there is a significant correlation between the key factors of the Hippo signaling pathway,suggesting that NF2 may regulate the Hippo signaling pathway with multiple regulatory mechanisms,and participate in the occurrence and development of colorectal cancer with the Hippo signaling pathway.4.NF2 and p-MST1/2 are protective factors affecting the prognosis of patients with colorectal cancer.