Research On The Expression Of SHH And YAP1 With Clinicopathological Characteristics Of Colorectal Cancer And Related Significance

Objective: Colorectal cancer is one of the most common malignancies in the world,and is the third and fourth most common cause of cancer-related mortality in the world respectively.In the past few decades,although in the diagnosis and treatment of colorectal cancer has made new progress,due to the early symptoms are not obvious to gastric cancer patients,so many patients at the time of diagnosis are already in the middle-late stage of the disease,thus missed the best period of treatment.Despite improvements resulting from the current standard of diagnosis and medical treatment,surgery,adjuvant chemotherapy combined with neoadjuvant chemoradiotherapy,the survival rate remains unsatisfactory in CRC patients.So finding biomarkers,that is related to colorectal cancer occurrence and development of colorectal cancer is of important significance to the early diagnosis and treatment of Colorectal cancer,which is conducive to prolonging the survival time and improving the prognosis of patients.In recent years,the relationship between Sonic Hedgehog(SHH)and Yes-associated protein 1(YAP1)and malignant tumors become a research hotspot,and the relationship between the two proteins and malignant tumors has brought its hot spot to its climax.Many study found that,SHH and YAP1 are related to the occurrence and development of a variety of malignant tumors.SHH and YAP1 are overexpressed in a variety of malignant tumors,including gastric cancer,breast cancer,lung cancer,hepatocellular carcinoma and prostate cancer,and herald a bad prognosis.SHH and YAP1 are play an important role to the growth and metastasis of the tumors.There is very few studies to explore the relationship between SHH and YAP1 and the progression and prognosis of colorectal cancer,and these researchs are controversial.We applied immunohistochemistry to detect SHH and YAP1 expression level in colorectal cancer tissues and non-cancerous tissues adjacent to the tumor,and used statistical methods to analyze the relationship between SHH and YAP1 expression and clinical pathological features,and to further explore its clinical significance.Methods: A retrospective cohort study including 351 colorectal cancer patients who were diagnosed and received surgery in the First Hospital of China Medical University from 2002 to 2008 was performed.All patients had not received preoperative chemotherapy or radiotherapy and other treatments.Immunohistochemical analysis was used to evaluate the expression of SHH and YAP1 in the 351 specimens of colorectal cancer tissues and 351 non-cancerous tissues adjacent to the tumor,and used statistical methods to analyze the relationship between SHH and YAP1 expression and clinicopathological characteristics and prognosis in colorectal cancer.The score of immunohistochemical staining used the double semiquantitative scoring method.Positive cell percentage scoring criteria:0(0-5%),1(6%-25%),2(26%-50%),3(51%-75%),or 4(>76%);Staining intensity scoring criteria:0(no stain),1(weak stain),2(moderate stain),or 3(strong stain).Staining intensity score multiplied by the positive cell percentage score as the final score.All data used SPSS V22.0 statistical software for analysis.Use nonparametric test to compare the difference between two groups of continuous variables.Application of chi-square analysis the correlation of count data,and application of Kaplan Meier survival curve for the survial analysis.a Cox regression model for multivariate analysis was applied to the factors that achieved significance in the univariate analysis.All statistical analyses were performed using SPSS 22.0 software.We used a 2-sided significance threshold of P<0.05 for all statistical analysis.Results: Immunohistochemistry(IHC)show that the SHH mainly located in cell membrane,YAP1 is mainly located in cytoplasm.We can find SHH and YAP1 expression in both colorectal cancer tissues and non-cancerous tissues adjacent to the tumor.But the level of SHH and YAP1 expression in colorectal cancers was significantly higher than in non-cancerous tissues adjacent to the tumor(PSHH<0.001;PYAP1<0.001).The specimens were then divided into high and low expression groups according to their score: SHH low expression(IS <5)and high expression(IS ? 5),and YAP1 low expression(IS <3)and high expression(IS ? 3).In the colorectal cancer tissues,there was significant correlation between SHH expression and TNM stage(P = 0.045),and had no obvious correlation with clinical pathologic factors related to patient's age,gender,differentiation,pT stage,pN stage and pM stage(P>0.05).There was significant correlation between SHH expression in the colorectal cancer tissues and patients' Lymph node metastasis and TNM stage(P = 0.045),and had no obvious correlation with clinical pathologic factors related to Patients' age,gender,differentiation degree,infiltration depth,transfer and distant organ metastasis(P>0.05).In addition,the Immunohistochemical score of SHH and YAP1 were statistically significant correlation.Conclusion: SHH or YAP1 expression in colorectal cancer tissues were significantly higher than those expression in non-cancerous tissues adjacent to the tumor(NATs),the co-expression of the two markers in CRC correlates to more advanced tumor stage.But SHH or YAP1 expression in colorectal cancer tissues and its prognosis has no obvious correlation.