Expression And Correlation Of PRR11 And CTHRC1 In Colorectal Cancer Tissues

Background:Colorectal Cancer（CRC）is a malignant tumor that occurs in the epithelium and glands of the colon and rectal mucosa.According to the latest national cancer statistics released by the National Cancer Center in January 2019,colorectal cancer ranks third in the incidence of malignant tumors in China,ranking fifth in the death of malignant tumors,and so far,it is still rising year by year^[1,2].There are about 1.2million newly diagnosed colorectal cancer patients in China each year,and more than600,000 people die directly or indirectly from colorectal cancer each year,which greatly reduces the quality of life of patients and increases the risk of death^[3,4].In recent years,despite the continuous improvement of the diagnosis and treatment of colorectal cancer,the surgical methods and adjuvant treatments continue to develop,but the overall efficacy has not improved significantly,the 5-year survival rate after surgery is about 30%to 50%,it is generally believed that the main reason is that at present there are still obvious deficiencies in the early diagnosis,postoperative recurrence and metastasis prevention and prognosis evaluation of colorectal cancer in China.The 5-year survival rate of patients with early colorectal cancer can reach 90%to 100%.However,there is still a lack of effective early diagnosis and prognosis methods in clinical practice today,and most patients are in the advanced stage of treatment^[5].In terms of prognosis assessment,traditional TNM staging is still an important basis for clinical work to judge prognosis^[6].However,the prognosis of patients with colorectal cancer who often have the same TNM staging is quite different.At present,for many patients with colorectal cancer with the same condition,the same or similar treatments are applied,but the actual therapeutic effects and adverse reactions are often very different.The existence of these individual differences is mostly due to the polymorphism of genes.The proline-rich protein 11,PRR11 gene is a newly identified oncogene potential gene that is highly expressed in a variety of tumors.Studies have shown that silencing PRR11 protein expression in tumor cells leads to E.cadherin Increased expression of epithelial markers and decreased expression of epithelial-mesenchymal transition（EMT）inducible factors（Snail,Slug,ZEB1,ZEB2,etc.）suggest that PRR11 protein expression promotes tumor cell transformation from epithelial phenotype to interstitial phenotype,and promote the occurrence and metastasis of tumors^[7].Collagen triple helix containing1（CTHRC1）is highly expressed in a variety of malignant tumors,and its carcinogenesis has been confirmed in a variety of malignant tumors.The mechanism of action may be that CTHRC1 protein can stably bind to Wnt-complex receptor to activates the Wnt signaling pathway^[8,9]and is directly involved in the EMT process^[10-12].But the co-expression and correlation analysis of PRR11 and CTHRC1 proteins in colorectal cancer,as well as PRR11 and CTHRC1 The mechanism of action of proteins in the development of colorectal cancer is still rarely reported.Objectives:To detect the expression of PRR11 and CTHRC1 protein in colorectal cancer tissues and adjacent tissues,and to analyze the relationship between the expression of PRR11 and CTHRC1 protein and different pathological features and prognosis of colorectal cancer.To explore the expression of PRR11 and CTHRC1 in colorectal cancer co-expression and correlation analysis,to provide new targets for early diagnosis,individualized treatment,metastasis intervention and prognosis of colorectal cancer patients.Materials and Methods:Colorectal cancer tissues and adjacent tissues specimens were taken from 68paraffin-embedded specimens of patients undergoing radical resection of colorectal cancer at the Affiliated Tumor Hospital of Zhengzhou University from July 2011 to July 2013.The colorectal cancer tissues were the experimental group,the adjacent tissues were the control group.Immunohistochemistry was used to detect the expression of PRR11 and CTHRC1 protein in the experimental group and the control group.The TNM staging was completed according to the 2017 NCCN guidelines.Combined with the postoperative pathology of patients with colorectal cancer,the PRR11 protein and CTHRC1 protein were analyzed byχ2 test to expression the differences between the experimental group and the control group,and the relationship between the expression of PRR11 and CTHRC1 protein and the clinicopathological features of patients with colorectal cancer was analyzed.The expression of PRR11 and CTHRC1 protein was analyzed by Kaplan-Meier method and Log-rank test to analyze the relationship between DFS and OS in patients with colorectal cancer after radical surgery.Pearson correlation analysis the PRR11 and CTHRC1 protein co-expression and correlation in colorectal cancer.Results:1.Of the 68 colorectal cancer tissues,39（57.35%）were positive for PRR11protein expression,and 15 of 68 adjacent cancer tissues were positive（22.06%）（P=0.000<0.05）.Among the 68 colorectal cancer tissues,43（63.2%）were positive for CTHRC1 protein expression,and 26（38.2%）of 68 adjacent cancer tissues were positive for CTHRC1 protein expression（P=0.004<0.05）.2.Among the 40 cases of high and moderately differentiated colorectal cancer tissues,18 cases were positive for PRR11 protein expression,and the expression rate was 45.00%.Among 28 low and undifferentiated colorectal cancer tissues,21 cases were positive for PRR11 protein expression.The rate was 75.00%,the difference was statistically significant（P=0.014<0.05）.In 25 cases of colorectal cancer tissues invading the muscular layer,19 cases were positive for PRR11 protein,the positive rate was 76.00%.In 43 cases of colorectal cancer tissues not invading the muscle layer,20 cases of PRR11 protein expression were positive,the positive rate was46.51%,the difference was statistically significant（P=0.018<0.05）;in 37 cases of TNM stage I,stage II knot among the rectal cancer tissues,13 cases were positive for PRR11 protein expression,and the positive rate was 35.14%.Among 31 cases of TNM stage III and IV colorectal cancer tissues,26 cases were positive,and the positive rate was 83.87%.The difference was statistically significant（P=0.000<0.05）.There was no significant difference in the expression of PRR11 protein in the age,sex,tumor location,tumor size,and lymph node metastasis group（P>0.05）.3.In 31 cases of colorectal cancer with lymph node metastasis,24 cases were positive for CTHRC1 protein,the positive rate was 77.42%.Among 37 cases of colorectal cancer without lymph node metastasis,19 cases were positive for CTHRC1protein,the positive rate was 51.35%,and the difference was statistically significant（P=0.026<0.05）.Among the 25 colorectal cancer tissues invading the muscular layer,22 cases were positive for CTHRC1 protein,and the positive rate was 88.00%.In 43cases of colorectal cancer tissues not invading the muscular layer,21 cases of CTHRC1 protein expression were positive,the positive rate was 48.84%,the difference was statistically significant（P=0.001<0.05）.37 cases of TNM stage were stage I,II stage among the colorectal cancer tissues,18 cases were positive for CTHRC1 protein expression,and the expression rate was 48.65%.In 31 cases of colorectal cancer tissues with stage TNM stage III and stage IV,25 cases of CTHRC1protein expression were positive,the positive rate was 80.65%,the difference was statistically significant（P=0.006<0.05）.There was no significant difference in the expression of CTHRC1 protein in the age,sex,tumor location,differentiation,tumor size group（P>0.05）.4.Patients with colorectal cancer were followed up by telephone follow-up at the end of follow-up with patient death,loss of follow-up or study deadline（July 1,2018）.A total of 63 patients were followed up,and the follow-up rate was 92.65%.In63 patients with colorectal cancer,the median DFS was 27.48 months in patients with positive PRR11 protein expression,and the median DFS was 43.31 months in patients with negative PRR11 protein expression.The difference was statistically significant（P<0.05）.The median DFS was 25.54 months in patients with positive CTHRC1protein expression,and the median DFS was 39.28 months in patients with negative CTHRC1 protein expression.The difference was statistically significant（P<0.05）.Of the 63 patients with colorectal cancer,29（46.03%）were positive for PRR11 and CTHRC1 protein,15（23.81%）were negative for PRR11 and CTHRC1 protein,and 8（12.70%）were positive for PRR11 protein,CTHRC1 negative protein expression,11cases（17.46%）negative PRR11 protein expression,CTHRC1 protein expression positive.Survival analysis showed that PRR11 and CTHRC1 protein both expression were positive,the median DFS was shorter,the difference was statistically significant（P=0.000<0.05）.However,the median OS of patients with colorectal cancer with PRR11 protein and CTHRC1 protein expression-positive colorectal cancer and the median OS of PRR11 and CTHRC1 protein-negative colorectal cancer patients,and the median OS of positive expression of both proteins was no significant difference（P>0.05）.5.Of the 68 colorectal cancer tissues,30（44.12%）cases were positive for PRR11 and CTHRC1 protein,16（23.53%）were negative for PRR11 and CTHRC1protein,and 9（13.23%）were PRR11 protein positive expression and negative expression of CTHRC1 protein,13（19.12%）negative PRR11 protein expression and CTHRC1 protein expression positive,the expression of both in colorectal cancer was significantly positive（r=0.392,P=0.007<0.05）.Conclusion:1.The positive expression rate of PRR11 and CTHRC1 protein in colorectal cancer tissues was significantly higher than that in adjacent tissues,indicating that both expressions were up-regulated in the development of colorectal cancer.2.In colorectal cancer tissues,the expression of PRR11 protein was significantly correlated with tumor differentiation,depth of invasion and TNM stage,and there is a clear correlation of the expression of CTHRC1 protein was associated with tumor lymph node metastasis,depth of invasion and TNM stage.3.Patients with colorectal cancer with positive PRR11 and CTHRC1 protein expression and positive expression of both proteins are shorter than those with negative expression,suggesting that positive expression of PRR11 and CTHRC1 may be a poor prognostic factor for patients with colorectal cancer.4.The expression of PRR11 and CTHRC1 protein in colorectal cancer tissues is positively correlated,suggesting that they may play a synergistic role in the development of colorectal cancer.